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Sample records for adequate blood circulation

  1. [Homeostasis in the gastric mucosa and blood circulation. Part 1. Mechanisms of the adequate blood flow maintenance in the gastric mucosa].

    PubMed

    Samonina, G E; Zhuĭkova, S E

    2001-01-01

    The increase of mucosal blood flow in response to food entrance into stomach or different irritant action is the component of gastric mucosal defence barrier. Sufficient blood flow ensures normal acid-bicarbonate balance in gastric mucosa, supports the healing process and prevents superficial damages from developing into deep ones. Capsaicin-sensitive afferent nerve fibers play the large role in the blood flow regulation. The influence of these nerve fibers on the gastric blood flow is mediated by the calcitonin-gene related peptide. This peptide released from peripheral afferent terminals improves microcirculation in stomach walls. Moreover nerve impulses from afferent neurons modulate parasympathetic activity that in turn induces the increase of gastric mucosal blood flow through both choilinergic and noncholinergic mechanisms. The gastric mucosal blood flow may be also regulated by humoral and paracrine metabolites. Nitric oxide and prostaglandines are the most important low molecular weight compounds. They play the main role in the maintenance of the basal gastric mucosal blood flow and in the development of hyperemic responses to harmful agents.

  2. Blood circulation under weightless conditions

    NASA Technical Reports Server (NTRS)

    Kasyan, I. I.; Kopanev, V. I.; Yazdovskiy, V. I.

    1975-01-01

    Biomedical data obtained on men and animals during weightlessness conditions establish instabilities in pulse rate and blood circulation that smooth out in proportion to adaptation to the weightless condition. The unusual slowness of recovery of pulse rate to initial values after space flight stress is attributed to biological simulation of hormonal shifts and discharge of humoral substances into the blood that prevent a rapid recovery of some biological indicators to initial values.

  3. Percentage of Adults with High Blood Pressure Whose Hypertension Is Adequately Controlled

    MedlinePlus

    ... is Adequately Controlled Percentage of Adults with High Blood Pressure Whose Hypertension is Adequately Controlled Heart disease ... Survey. Age Group Percentage of People with High Blood Pressure that is Controlled by Age Group f94q- ...

  4. A blood circulation model for reference man

    SciTech Connect

    Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

    1999-01-01

    This paper describes a dynamic blood circulation model that predicts the movement and gradual dispersal of a bolus of material in the circulation after its intravascular injection into an adult human. The main purpose of the model is to improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The total blood volume is partitioned into the blood contents of 24 separate organs or tissues, right heart chambers, left heart chambers, pulmonary circulation, arterial outflow to the systemic tissues (aorta and large arteries), and venous return from the systemic tissues (large veins). As a compromise between physical reality and computational simplicity, the circulation of blood is viewed as a system of first-order transfers between blood pools, with the delay time depending on the mean transit time across the pool. The model allows consideration of incomplete, tissue-dependent extraction of material during passage through the circulation and return of material from tissues to plasma.

  5. 76 FR 51041 - Hemoglobin Standards and Maintaining Adequate Iron Stores in Blood Donors; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... HUMAN SERVICES Food and Drug Administration Hemoglobin Standards and Maintaining Adequate Iron Stores in... Standards and Maintaining Adequate Iron Stores in Blood Donors.'' The purpose of this public workshop is to... donor safety and blood availability, and potential measures to maintain adequate iron stores in...

  6. A blood circulation model for reference man

    SciTech Connect

    Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

    1996-12-31

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86.

  7. Blood vessels, circulation and blood pressure.

    PubMed

    Hendry, Charles; Farley, Alistair; McLafferty, Ella

    This article, which forms part of the life sciences series, describes the vessels of the body's blood and lymphatic circulatory systems. Blood pressure and its regulatory systems are examined. The causes and management of hypertension are also explored. It is important that nurses and other healthcare professionals understand the various mechanisms involved in the regulation of blood pressure to prevent high blood pressure or ameliorate its damaging consequences.

  8. Blood circulation under conditions of weightlessness

    NASA Technical Reports Server (NTRS)

    Kastyan, I. I.; Kopanev, V. I.

    1980-01-01

    Experimental materials and published data on the problem of blood circulation in man and animals under conditions of short and long term weightlessness are summarized. The data obtained allow the conclusion, that when humans spent 5 days in a weightless state their blood circulation was not essentially distributed. Some features of the functioning of the cardiovascular system are pointed out: delay of adaptation rate, increase in lability, etc. There is a discussion of the physiological mechanisms for the direct and indirect effect of weightlessness. The direct effect comprise the complex of reactions caused by the significant fall in hydrostatic pressure and the indirect embraces all the reactions arising in the organism resulting from disturbance of the systematic character of the analyzers that take part in the analysis of space realtions and the body's orientation in space.

  9. [William Harvey, discoverer of the blood circulation].

    PubMed

    v Mühlendahl, K E

    2007-06-01

    William Harvey (1578-1657), living at the turn to modern times, scientifically speaking, was an eminent physician and scientist. He developed the concept of the circulation of the blood and his findings have proved to be correct in nearly all details to this day. He published his physiological findings and interpretations in a small, albeit epoch-making, volume: Exercitatio anatomica de motu cordis et sanguinis in animalibus, published in Frankfurt in 1628. On the occasion of the 350th anniversary of his death on June 3, 2007, this essay commemorates the work of this important physician, illustrating his brilliant conception of the blood circulation by quoting passages from De motu cordis et sanguinis.

  10. Cancer cells in the circulating blood

    PubMed Central

    Sato, Haruo

    1962-01-01

    The author discusses the relation between the presence of cancer cells in the circulating blood and the development of metastasis, as demonstrated by studies on animals with experimentally induced tumours, by post-mortem studies on fatal human cases of cancer, and by studies on patients operated upon for stomach cancer. Although the correlation between the presence of tumour cells in the blood and the occurrence of metastatic lesions was found to be less close in the human cases of cancer than in the experimental animals, the author considers that it was sufficiently marked to justify the assumption that the appearance of tumour cells in the circulating blood is an important link in the chain of processes leading to cancer metastasis. In conclusion, the author puts forward the suggestion, based on the results of animal experiments, that chemotherapy might have an inhibitory effect on the liberated tumour cells in the blood, particularly if these cells are present only in small numbers, and thus be instrumental in halting the course of metastasis. PMID:14497407

  11. [Who really first described lesser blood circulation?].

    PubMed

    Masić, Izet; Dilić, Mirza

    2007-01-01

    Today, at least 740 years since professor and director of the Al Mansouri Hospital in Cairo Ibn al-Nafis (1210-1288), in his paper about pulse described small (pulmonary) blood circulatory system. At the most popular web search engines very often we can find its name, especially in English language. Majority of quotes about Ibn Nefis are on Arabic or Turkish language, although Ibn Nefis discovery is of world wide importance. Author Masić I. (1993) is among rare ones who in some of the indexed journals emphasized of that event, and on that debated also some authors from Great Britain and USA in the respectable magazine Annals of Internal Medicine. Citations in majority mentioning other two "describers" or "discoverers" of pulmonary blood circulation, Michael Servetus (1511-1553), physician and theologist, and William Harvey (1578-1657), which in his paper "Exercitatio anatomica de motu cordis et sanguinis in animalibus" published in 1628 described blood circulatory system. Ibn Nefis is due to its scientific work called "Second Avicenna". Some of his papers, during centuries were translated into Latin, and some published as a reprint in Arabic language. Professor Fuat Sezgin from Frankfurt published a compendium of Ibn Nefis papers in 1997. Also, Masić I. (1997) has published one monography about Ibn Nefis. Importance of Ibn Nefis epochal discovery is the fact that it is solely based on deductive impressions, because his description of the small circulation is not occurred by observation on corps during section. It is known that he did not pay attention to the Galen's theories about blood circulation. His prophecy sentence say: "If I don't know that my work will not last up to ten thousand years after me, I would not write them". Sapient sat.

  12. Metalloprotease-dependent onset of blood circulation in zebrafish.

    PubMed

    Iida, Atsuo; Sakaguchi, Kazuya; Sato, Kiyoaki; Sakurai, Hidetoshi; Nishimura, Daigo; Iwaki, Aya; Takeuchi, Miki; Kobayashi, Makoto; Misaki, Kazuyo; Yonemura, Shigenobu; Kawahara, Atsuo; Sehara-Fujisawa, Atsuko

    2010-06-22

    The primitive blood circulation requires intravascular plasma flow. However, it remains unclear whether the onset of earliest blood circulation is dependent solely on establishment of a functional circulatory organ or whether it also requires active processes inherent in blood cells. In this study, we present novel mechanisms for the onset of blood circulation by monitoring fluorescently labeled blood precursors and blood vessels in zebrafish. The earliest blood circulation occurs synchronously. This synchrony is achieved by the retention of erythroid precursors on the lumen of the vasculature after their invasion from the subaortic region, and then by simultaneous release of these precursors into the flow. Morphological and biochemical analyses suggest that the onset of blood circulation accompanies disruption of blood cell-to-vessel adhesion and requires metalloprotease-dependent processes. ADAM8, a member of the a disintegrin and metalloprotease (ADAM) family, mediates the onset of blood circulation. In ADAM8-depleted embryos, erythroid cells fail to detach from the vascular lumen and stagnate. Expression of a protease-defective ADAM8 in erythroid cells causes dominant-negative effects on blood circulation, suggesting cell-autonomous roles of ADAM8. Based on these findings, we propose that the first erythroid cells require both flow-dependent passive and proteolysis-dependent active processes to enter the circulation.

  13. Prevalence of Blood Circulation Misconceptions among Prospective Elementary Teachers

    ERIC Educational Resources Information Center

    Pelaez, Nancy J.; Boyd, Denise D.; Rojas, Jacqueline B.; Hoover, Mildred A.

    2005-01-01

    Research shows that misconceptions about human blood circulation and gas exchange persist across grade levels. The purpose of this study was twofold: (1) to investigate the prevalence and persistence of blood circulation misconceptions among prospective elementary teachers; and (2) to evaluate the effectiveness of learning activities for…

  14. The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study

    PubMed Central

    Goutianos, Georgios; Tzioura, Aikaterini; Kyparos, Antonios; Paschalis, Vassilis; Margaritelis, Nikos V; Veskoukis, Aristidis S; Zafeiridis, Andreas; Dipla, Konstantina; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2015-01-01

    Animal models are widely used in biology and the findings of animal research are traditionally projected to humans. However, recent publications have raised concerns with regard to what extent animals and humans respond similar to physiological stimuli. Original data on direct in vivo comparison between animals and humans are scarce and no study has addressed this issue after exercise. We aimed to compare side by side in the same experimental setup rat and human responses to an acute exercise bout of matched intensity and duration. Rats and humans ran on a treadmill at 86% of maximal velocity until exhaustion. Pre and post exercise we measured 30 blood chemistry parameters, which evaluate iron status, lipid profile, glucose regulation, protein metabolism, liver, and renal function. ANOVA indicated that almost all biochemical parameters followed a similar alteration pattern post exercise in rats and humans. In fact, there were only 2/30 significant species × exercise interactions (in testosterone and globulins), indicating different responses to exercise between rats and humans. On the contrary, the main effect of exercise was significant in 15/30 parameters and marginally nonsignificant in other two parameters (copper, P = 0.060 and apolipoprotein B, P = 0.058). Our major finding is that the rat adequately mimics human responses to exercise in those basic blood biochemical parameters reported here. The physiological resemblance of rat and human blood responses after exercise to exhaustion on a treadmill indicates that the use of blood chemistry in rats for exercise physiology research is justified. PMID:25677548

  15. Evaluation of catheter-manometer systems for adequate intravascular blood pressure measurements in small animals.

    PubMed

    Idvall, J; Aronsen, K F; Lindström, K; Ulmsten, U

    1977-09-30

    Various catheter-manometer systems possible for intravascular blood pressure measurments on rats have been elaborated and tested in vitro and in vivo. Using a pressure-step calibrator, it was observed from in vitro studies that microtransducers had superior frequency response compared to conventional transducers. Of the catheters tested, Pe-90 tapered to a 40 mm tip with an inner diameter of 0.3 mm had the best frequency response as judged from fall and settling times. Because of the damping effect, tapering increased fall time to 1.8 ms, which was still quite acceptable. By the same token settling time was minimized to 22.4 ms. With a special calculation method the theoretical percentile fault of the recordings was estimated to be 9.66%. When the measurement error was calculated from the actual in vivo recordings, it was found to be no more than 2.7%. These results show that the technique described is adequate for continuous intravascular blood pressure recordings on small animals. Finally it is emphasized that careful handling of the catheters and avoidance of stopcocks and air bubbles are essential for obtaining accurate and reproducible values. PMID:928971

  16. Prevalence of blood circulation misconceptions among prospective elementary teachers.

    PubMed

    Pelaez, Nancy J; Boyd, Denise D; Rojas, Jacqueline B; Hoover, Mildred A

    2005-09-01

    Research shows that misconceptions about human blood circulation and gas exchange persist across grade levels. The purpose of this study was twofold: 1) to investigate the prevalence and persistence of blood circulation misconceptions among prospective elementary teachers and 2) to evaluate the effectiveness of learning activities for discovering what students know and can explain about blood circulation and lung function. The context was an undergraduate introduction to biology course taught by two professors across three semesters at a state university. Independent reviewers identified five categories of erroneous ideas about blood circulation. Many categories still presented problems to students at the end of the course: 70% of prospective elementary teachers did not understand the dual blood circulation pathway, 33% were confused about blood vessels, 55% had wrong ideas about gas exchange, 19% had trouble with gas transport and utilization, and 20% did not understand lung function. Results show that an interview about a drawing as a final exam was significantly better at revealing different errors and a higher frequency of erroneous ideas compared with an essay exam. There is an urgent need for instructional tools to help undergraduate students realize the discrepancies between their own ideas about blood circulation and those of the scientific community.

  17. A COMPARITIVE STUDY ON CONCEPTS OF CIRCULATION OF BLOOD

    PubMed Central

    Pandey, V.N.; Pandey, Ayodhya

    1990-01-01

    This study traces the progressively evolving concepts of blood circulation. Evidences from medical and non-medical Sanskrit literature have been presented to high the fact that the Ayurvedic concepts of physiology are time tested. PMID:22557695

  18. [Mandible regional blood circulation peculiarities by dental implants placement].

    PubMed

    Malanchuk, V A; Tsilenko, O L; Grabovetskiĭ, P V

    2013-01-01

    The paper presents data on regional blood circulation in mandible implant placement sites. Rheographic assessment in 50 patients divided in two groups according to implant placement protocol revealed that circulation volume and peripheral vessels tonus restored on the 14th day after implant placement with wound draining while in conventional implant placement protocol these values remained disturbed even 21 days after surgical procedure.

  19. Salt, blood pressure and cardiovascular risk: what is the most adequate preventive strategy? A Swiss perspective

    PubMed Central

    Burnier, Michel; Wuerzner, Gregoire; Bochud, Murielle

    2015-01-01

    Among the various strategies to reduce the incidence of non-communicable diseases reduction of sodium intake in the general population has been recognized as one of the most cost-effective means because of its potential impact on the development of hypertension and cardiovascular diseases. Yet, this strategic health recommendation of the WHO and many other international organizations is far from being universally accepted. Indeed, there are still several unresolved scientific and epidemiological questions that maintain an ongoing debate. Thus what is the adequate low level of sodium intake to recommend to the general population and whether national strategies should be oriented to the overall population or only to higher risk fractions of the population such as salt-sensitive patients are still discussed. In this paper, we shall review the recent results of the literature regarding salt, blood pressure and cardiovascular risk and we present the recommendations recently proposed by a group of experts of Switzerland. The propositions of the participating medical societies are to encourage national health authorities to continue their discussion with the food industry in order to reduce the sodium intake of food products with a target of mean salt intake of 5–6 grams per day in the population. Moreover, all initiatives to increase the information on the effect of salt on health and on the salt content of food are supported. PMID:26321959

  20. Systemic modelling of human bioenergetics and blood circulation.

    PubMed

    Lim, K M; Yang, S-H; Shim, E B

    2012-10-01

    This work reviews the main aspects of human bioenergetics and the dynamics of the cardiovascular system, with emphasis on modelling their physiological characteristics. The methods used to study human bioenergetics and circulation dynamics, including the use of mathematical models, are summarised. The main characteristics of human bioenergetics, including mitochondrial metabolism and global energy balance, are first described, and the systemic aspects of blood circulation and related physiological issues are introduced. The authors also discuss the present status of studies of human bioenergetics and blood circulation. Then, the limitations of the existing studies are described in an effort to identify directions for future research towards integrated and comprehensive modelling. This review emphasises that a multi-scale and multi-physical approach to bioenergetics and blood circulation that considers multiple scales and physiological factors are necessary for the appropriate clinical application of computational models.

  1. Circulation of blood through the heart (image)

    MedlinePlus

    ... Blood comes into the right atrium from the body, moves into the right ventricle and is pushed into the pulmonary arteries in the lungs. After picking up oxygen, the ... left ventricle and out to the body's tissues through the aorta.

  2. [Peripheral blood circulation in the skin and the regulatory mechanisms in the course of primary transmural myocardial infarction].

    PubMed

    Khalepo, O V; Molotkov, O V; Eshkina, S L

    2009-01-01

    Laser Doppler flowmetry was used to study the indicators characterizing the peripheral blood circulation in the skin, regulatory mechanisms, and the compensatory capacities of the microcirculatory bed in 32 patients aged 45-60 years in the course of primary transmural myocardial infarction during exercise tests. Significant disturbances of the mechanism responsible for regulating the peripheral blood circulation system and chiefly its active components were detected in the presence of adequate blood filling of microvessels. There was a drastic decrease in the reserves of skin microvascular endothelial activity during ionophoresis of sodium nitroprusside and acetylcholine, the maximum degree of disturbances being observed on day 10 of myocardial infarction development.

  3. Hybrid polyglycerols with long blood circulation: synthesis, biocompatibility, and biodistribution.

    PubMed

    Imran ul-haq, Muhammad; Lai, Benjamin F L; Kizhakkedathu, Jayachandran N

    2014-10-01

    Multifunctional polymers with defined structure and biocompatibility are critical to the development of drug delivery systems and bioconjugates. In this article, the synthesis, in vitro blood compatibility, cell viability, in vivo circulation, biodistribution, and clearance of hybrid copolymers based on linear and branched polyglycerol are reported. Hybrid polyglycerols (M(n) ≈ 100 kDa) are synthesized with different compositions (15-80 mol% linear polyglycerol). Relatively small hydrodynamic size and radius of gyration of the hybrid polyglycerols suggest that they are highly compact functional nanostructures. The hybrid polyglycerols show excellent blood compatibility as determined by measuring their effects on blood coagulation, red blood cell aggregation, hemolysis, platelet, and complement activation. The cell viability in presence of hybrid polyglycerols is excellent up to 10 mg mL(-1) concentration and is similar to both dextran and polyvinyl alcohol. Furthermore, tritium labeled hybrid polyglycerol shows long blood circulation (t(1/2β)= 34 h) with minimal organ accumulation in mice. Multifunctionality, compact nature, biocompatibility, and the long blood circulation make these polymers attractive for the development of bioconjugates and drug delivery systems.

  4. Non-invasive glycaemia blood measurements by electromagnetic sensor: study in static and dynamic blood circulation.

    PubMed

    Gourzi, M; Rouane, A; Guelaz, R; Alavi, M S; McHugh, M B; Nadi, M; Roth, P

    2005-01-01

    In this paper, we present the results of non-invasive blood glycaemia measurements. The blood used in the measurements was calf blood. The measurement method uses an electromagnetic sensor based on eddy currents, which allows the detection of blood glycaemia levels through the variation of the dielectric parameters of the blood. A change in blood glucose concentration causes a variation in the dielectric parameters, in particular conductivity. Detection is only possible at a resonant frequency. The measurements were taken in a static and dynamic state (with and without circulation of blood). The blood is inside a plastic tube placed within the sensor and is surrounded by gelatine, which simulates muscular tissue. The plastic tube simulates the vein where blood circulation occurs. The in vitro results in both cases (static and dynamic) are provided. Under unfavourable conditions we can detect a change of +/- 2 g/l of glucose. We present and discuss these results.

  5. [Applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis].

    PubMed

    Wang, Feng-Qin; Chen, Cen; Xia, Zhi-Ning; Yang, Feng-Qing

    2014-08-01

    Thrombotic diseases in different forms become a great threat to human health. Such anti-platelet aggregation drugs as aspirin and clopidogrel are common drugs in clinic. However, along with the appearance of resistance and side effects of western anti-platelet aggregation drugs, anti-platelet aggregation traditional Chinese medicines promoting blood circulation to remove blood stasis have gradually become an important study orientation. Platelet is one of major participant in thrombosis, and plays an important role as a bioactive material in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, mainly involving two aspects--the evaluation for the anti-platelet aggregation activity of traditional Chinese medicines and the screening of their active components. This paper summarized the applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, so as to provide basis for further studies.

  6. Ultrasonic Doppler blood flow meter for extracorporeal circulation

    NASA Astrophysics Data System (ADS)

    Dantas, Ricardo G.; Costa, Eduardo T.; Maia, Joaquim M.; Nantes Button, Vera L. d. S.

    2000-04-01

    In cardiac surgeries it is frequently necessary to carry out interventions in internal heart structures, and where the blood circulation and oxygenation are made by artificial ways, out of the patient's body, in a procedure known as extracorporeal circulation (EC). During this procedure, one of the most important parameters, and that demands constant monitoring, is the blood flow. In this work, an ultrasonic pulsed Doppler blood flowmeter, to be used in an extracorporeal circulation system, was developed. It was used a 2 MHz ultrasonic transducer, measuring flows from 0 to 5 liters/min, coupled externally to the EC arterial line destined to adults perfusion (diameter of 9.53 mm). The experimental results using the developed flowmeter indicated a maximum deviation of 3.5% of full scale, while the blood flow estimator based in the rotation speed of the peristaltic pump presented deviations greater than 20% of full scale. This ultrasonic flowmeter supplies the results in a continuous and trustworthy way, and it does not present the limitations found in those flowmeters based in other transduction methods. Moreover, due to the fact of not being in contact with the blood, it is not disposable and it does not need sterilization, reducing operational costs and facilitating its use.

  7. [Neural control of the peripheral circulation and blood pressure].

    PubMed

    Estañol, Bruno; Porras-Betancourt, Manuel; Sánchez-Torres, Gustavo; Martínez-Memije, Raúl; Infante, Oscar; Sentíes-Madrid, Horacio

    2009-12-01

    In the XIX century Claude Bernard discovered the action of the nervous system on the peripheral circulation. In the first half of the XX century Ewald Hering discovered the baro-receptor and the reflex control of the heart rate and blood pressure. Cowley and Guyton demonstrated that sino-aortic denervation induces persistent changes in the blood pressure in the dog. The autonomic nervous system is mainly responsible for the regulation of the circulation and blood pressure in the short term on a beat to beat basis. It controls the vasomotor tone, the heart rate and the cardiac output. With the advent of non invasive methods that measure the blood pressure on a beat to beat basis (Finapres) and with the methods of measurement of the variability of the blood pressure in the frequency domain (spectral analysis) we can currently measure many variables including heart rate, blood pressure, stroke volume, peripheral resistances and the baroreceptor sensitivity and make some inferences about their control mechanisms. These variables can be measured at rest in the supine position, standing up, during rhythmic breathing and during the Valsalva maneuver. In this article we present a review of the neural control of the blood pressure and heart rate.

  8. Circulating Vitamin D3 and 25-hydroxyvitamin D in Humans: An Important Tool to Define Adequate Nutritional Vitamin D Status

    PubMed Central

    Hollis, Bruce W.; Wagner, Carol L.; Drezner, Mark K.; Binkley, Neil C.

    2007-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D3 and its metabolic product—25(OH)D3 has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6,400 IU vitamin D3/day for six months. Results: 1) The relationship between circulating vitamin D3 and 25(OH)D in both groups was not linear, but appeared saturable and controlled; 2) Optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D3 and 25(OH)D exceeded 0.3; at this point, the Vmax of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol. We hypothesize that as humans live today, the 25-hydroxylase operates well below its Vmax because of chronic substrate deficiency, namely vitamin D3. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be. PMID:17218096

  9. Metabolism of nanomaterials in vivo: blood circulation and organ clearance.

    PubMed

    Wang, Bing; He, Xiao; Zhang, Zhiyong; Zhao, Yuliang; Feng, Weiyue

    2013-03-19

    Before researchers apply nanomaterials (NMs) in biomedicine, they need to understand the blood circulation and clearance profile of these materials in vivo. These qualities determine the balance between nanomaterial-induced activity and unwanted toxicity. NMs have heterogeneous characteristics: they combine the bulk properties of solids with the mobility of molecules, and their highly active contact interfaces exhibit diverse functionalities. Any new and unexpected circulation features and clearance patterns are of great concern in toxicological studies and pharmaceutical screens. A number of studies have reported that NMs can enter the bloodstream directly during their application or indirectly via inhalation, ingestion, and dermal exposure. Due to the small size of NMs, the blood can then transport them throughout the circulation and to many organs where they can be stored. In this Account, we discuss the blood circulation and organ clearance patterns of NMs in the lung, liver, and kidney. The circulation of NMs in bloodstream is critical for delivery of inhalable NMs to extrapulmonary organs, the delivery of injectable NMs, the dynamics of tissue redistribution, and the overall targeting of drug carriers to specific cells and organs. The lung, liver, and kidney are the major distribution sites and target organs for NMs exposure, and the clearance patterns of NMs in these organs are critical for understanding the in vivo fate of NMs. Current studies suggest that multiple factors control the circulation and organ clearance of NMs. The size, shape, surface charge, surface functional groups, and aspect ratio of NMs as well as tissue microstructures strongly influence the circulation of NMs in bloodstream, their site-specific extravasation, and their clearance profiles within organs. Therefore structure design and surface modification can improve biocompatibility, regulate the in vivo metabolism, and reduce the toxicity of NMs. The biophysicochemical interactions

  10. [Regulation of innate immunity during xenogenic changes in blood circulation].

    PubMed

    Shevchenko, V S

    2001-01-01

    Calcium-dependent innate immune response with participation of the superfamily of immunoglobulins to several intra- and extracorporal xenobiotics were studied at 216 recipients during synthetic cardiac valves implantation or veins transplantation in coronary arteries. It was shown that immediate immune response to xenobiotics was manifested by generation of the antitissue anodical autoprecipitin with specificity to the surface cell membrane component. This reaction initiated and regulated the subsequent dynamics of the two different fibrinogen autoimmune complexes formation, resulting in development of the immunogenic damages of blood circulation. Correction of these rapid innate immune responses is important for prevention and normalisation of the xenogenic damages of blood circulation during trans- and implantation on the heart impaired with endocarditis or aterosclerosis.

  11. Completing the puzzle of blood circulation: the discovery of capillaries.

    PubMed

    Karamanou, Marianna; Androutsos, George

    2010-01-01

    Marcello Malpighi is considered to be the founder of microscopic anatomy. For almost 40 years he used the newly invented microscope to study and discover many structures of human body, animals and plants. One of his greatest contributions to science was the establishment by direct observation of an anatomical linkage between arteries and veins, the capillary network, a monumental work that completed Harvey's theory of blood circulation.

  12. Harvey, by Hercules! The hero of the blood's circulation.

    PubMed

    O'Rourke Boyle, Marjorie

    2013-01-01

    This article continues the analyses in Medical History 52 (2008), 73-90, 365-86 of William Harvey's self-understanding as the philosopher and discoverer of the blood's circulation. Harvey brilliantly and subversively assumed the persona of the mythological Hercules to embody his own anatomical labour in De motu cordis et sanguinis (1628). He reprised the role in self-defence against accusations in the College of Physicians, London, of his breach of faith with medical tradition. Harvey sought to usurp the medical epithet 'a second Hercules' by reforming humanist dependence on ancient texts as authoritative medicine. A knowledge of the theory and practice of Renaissance humanism discloses his identification with the Herculean labour of cleansing the Augean stable. He employed anatomical demonstration against Galen's porous cardiac septum, which admitted blood across the ventricles. Harvey's oath mehercule swore against Galen's Dia to assert the necessity of opening an alternate route for the blood flow. His Herculean labour was to dam the cardiac septum and divert the blood flow into a continuous channel through the arteries and veins. His circulation of the blood also imitated Hercules' successful dependence on the force of the water flow to flush the Augean stable. Harvey's copia did not denote a quantitative amount but a powerful supply. Harvey aspired to be, like Hercules, immortal, a term which the College belatedly acknowledged. This cultural analysis exposes Harvey's professional issues and personal ambitions, so to promote a fuller understanding of his historic role in medical discovery.

  13. The effect of oral uptake of nicotine in snus on peripheral skin blood circulation evaluated by thermography

    PubMed Central

    Høiland, Ina Isabella; de Weerd, Louis; Mercer, James B

    2014-01-01

    While health risks from smoking cigarettes are well known, little is known about the health risks of using smokeless tobacco (ST). The aim of this study was to evaluate the effect that ST in the form of oral use of snus with nicotine and snus without nicotine has on peripheral skin blood circulation. 21 young habitual users of snus with nicotine participated in this study. Under controlled conditions the subjects were exposed to a 30 minute period of oral use of snus with nicotine (SN+) and snus without nicotine (SN-). The peripheral skin blood circulation was indirectly monitored on the hands by measuring skin temperature using infrared thermography. The skin blood circulation in the hands showed a statistical significant decrease in the SN+ experiments, while skin blood circulation was hardly effected in the SN- experiments. It is concluded that the use of smokeless tobacco in the form of oral use of snus containing nicotine causes a decrease in peripheral skin blood circulation while such an effect is not seen in snus without nicotine. This knowledge may be of use when treating patients that require adequate peripheral skin circulation or in the military when soldiers are exposed cold conditions.

  14. The effect of oral uptake of nicotine in snus on peripheral skin blood circulation evaluated by thermography.

    PubMed

    Høiland, Ina Isabella; de Weerd, Louis; Mercer, James B

    2014-01-01

    While health risks from smoking cigarettes are well known, little is known about the health risks of using smokeless tobacco (ST). The aim of this study was to evaluate the effect that ST in the form of oral use of snus with nicotine and snus without nicotine has on peripheral skin blood circulation. 21 young habitual users of snus with nicotine participated in this study. Under controlled conditions the subjects were exposed to a 30 minute period of oral use of snus with nicotine (SN+) and snus without nicotine (SN-). The peripheral skin blood circulation was indirectly monitored on the hands by measuring skin temperature using infrared thermography. The skin blood circulation in the hands showed a statistical significant decrease in the SN+ experiments, while skin blood circulation was hardly effected in the SN- experiments. It is concluded that the use of smokeless tobacco in the form of oral use of snus containing nicotine causes a decrease in peripheral skin blood circulation while such an effect is not seen in snus without nicotine. This knowledge may be of use when treating patients that require adequate peripheral skin circulation or in the military when soldiers are exposed cold conditions.

  15. Determining which automatic digital blood pressure device performs adequately: a systematic review

    PubMed Central

    Wan, Y; Heneghan, C; Stevens, R; McManus, R J; Ward, A; Perera, R; Thompson, M; Tarassenko, L; Mant, D

    2010-01-01

    The aim of this study is to systematically examine the proportion of accurate readings attained by automatic digital blood pressure (BP) devices in published validation studies. We included studies of automatic digital BP devices using recognized protocols. We summarized the data as mean and s.d. of differences between measured and observed BP, and proportion of measurements within 5 mm Hg. We included 79 articles (10 783 participants) reporting 113 studies from 22 different countries. Overall, 25/31 (81%), 37/41 (90%) and 34/35 (97%) devices passed the relevant protocols [BHS, AAMI and ESH international protocol (ESH-IP), respectively]. For devices that passed the BHS protocol, the proportion of measured values within 5 mm Hg of the observed value ranged from 60 to 86% (AAMI protocol 47–94% and ESH-IP 54–89%). The results for the same device varied significantly when a different protocol was used (Omron HEM-907 80% of readings were within 5 mm Hg using the AAMI protocol compared with 62% with the ESH-IP). Even devices with a mean difference of zero show high variation: a device with 74% of BP measurements within 5 mm Hg would require six further BP measurements to reduce variation to 95% of readings within 5 mm Hg. Current protocols for validating BP monitors give no guarantee of accuracy in clinical practice. Devices may pass even the most rigorous protocol with as few as 60% of readings within 5 mm Hg of the observed value. Multiple readings are essential to provide clinicians and patients with accurate information on which to base diagnostic and treatment decisions. PMID:20376077

  16. IR imaging of blood circulation of patients with vascular disease

    NASA Astrophysics Data System (ADS)

    Wang, Hsin; Wade, Dwight R., Jr.; Kam, Jack

    2004-04-01

    We conducted a preliminary IR imaging study of blood circulation in patients with peripheral vascular diseases. Abnormal blood flow is common in older adults, especially those with elevated blood lipids, diabetes, hypertension, and a history of smoking. All of these conditions have a high prevalence in our population, often with more than one condition in the same individual. The differences in blood flow is revealed by temperature differences in areas of the extremities as well as other regions of the body. However, what is needed is an imaging technique that is relatively inexpensive and can reveal the blood flow in real time. The IR imaging can show detailed venous system and small tempearture changes associated with blood flow. Six patients with vascular diseases were tested in a clinic set up. Their legs and feet were imaged. We observed large temperature differences (cooling of more than 10° C) at the foot, especially toes. More valuable information were obtained from the temperature distribution maps. IR thermography is potentially a very valuable tool for medical application, especially for vascular diseases.

  17. [Endothelial glycocalyx of blood circulation. I. Finding, components, structure organization].

    PubMed

    Maksimenko, A V; Turashev, A D

    2014-01-01

    In normal state, a complex multicomponent system called glycocalyx is present on the surface of endothelial vascular system. The structure of the glycocalyx is determined by a group ofproteoglycans, glycoproteins and glycosaminoglycans, originating from endothelial cells and blood flow. Due to its complexity and location on the border of the system of blood circulation, glycocalyx participates in a number of functions supporting the metabolism of the vascular wall. Complete or partial loss of this structure in pathologicalconditions leads to inconsistencies in the vascular wall and changes in its functions. The first part of this review considers the history of detection and determination of endothelial glycocalyx structure, utilized methods and approaches. The molecular composition of the glycocalyx, properties of its components and glycocalyx structure organization are described. The English version of the paper: Russian Journal of Bioorganic Chemistry, see also http://www.maik.ru.

  18. Does Every Cell Get Blood? Young Students' Discussions about Illustrations of Human Blood Circulation

    ERIC Educational Resources Information Center

    Westman, Anna-Karin; Karlsson, Karl-Goran

    2016-01-01

    This article presents a study of how groups of young students discuss illustrations of human blood circulation. Transparency is not an innate quality of illustrations, visual information is always coded and interpretations are always related to culture and context. Results of this study are discussed with reference to Kress and van Leeuwens'…

  19. Blood transcriptomes reveal novel parasitic zoonoses circulating in Madagascar's lemurs.

    PubMed

    Larsen, Peter A; Hayes, Corinne E; Williams, Cathy V; Junge, Randall E; Razafindramanana, Josia; Mass, Vanessa; Rakotondrainibe, Hajanirina; Yoder, Anne D

    2016-01-01

    Zoonotic diseases are a looming threat to global populations, and nearly 75% of emerging infectious diseases can spread among wildlife, domestic animals and humans. A 'One World, One Health' perspective offers us an ideal framework for understanding and potentially mitigating the spread of zoonoses, and the island of Madagascar serves as a natural laboratory for conducting these studies. Rapid habitat degradation and climate change on the island are contributing to more frequent contact among humans, livestock and wildlife, increasing the potential for pathogen spillover events. Given Madagascar's long geographical isolation, coupled with recent and repeated introduction of agricultural and invasive species, it is likely that a number of circulating pathogens remain uncharacterized in lemur populations. Thus, it is imperative that new approaches be implemented for de novo pathogen discovery. To this end, we used non-targeted deep sequencing of blood transcriptomes from two species of critically endangered wild lemurs (Indri indri and Propithecus diadema) to characterize blood-borne pathogens. Our results show several undescribed vector-borne parasites circulating within lemurs, some of which may cause disease in wildlife, livestock and humans. We anticipate that advanced methods for de novo identification of unknown pathogens will have broad utility for characterizing other complex disease transmission systems. PMID:26814226

  20. [Effect of exercise in water on maternal blood circulation].

    PubMed

    Asai, M; Saegusa, S; Yamada, A; Suzuki, M; Noguchi, M; Niwa, S; Nakanishi, M

    1994-02-01

    To elucidate the effects of exercise in water on the maternal circulation, twenty normal pregnancies were examined under the following three conditions; 1) on the land at rest, 2) during water immersion and 3) after the exercise in water. Their gestational ages were from 25 to 37 weeks (31 +/- 4 weeks, mean +/- S.D., n = 20). We examined the blood pressure, the urine volume throughout the examination, CBC and the levels of vasopressin, plasma renin activity and human atrial natriuretic peptide (hANP). The blood volume calculated from the Hb and Ht were significantly (p < 0.001) increased during the water immersion (105.8 +/- 2.5%), even after the exercise (101.6 +/- 2.9%). Vasopressin was decreased during the water immersion and increased after the exercise, but plasma renin activity was decreased in these two conditions. The hANP concentration was significantly (p < 0.001) increased after the exercise in water and correlated with the urine volume (ml/hour) during the examination. These results show that the decline in blood pressure and the increase in the urine volume during the maternal swimming were caused by the decreased plasma renin activity and the increased hANP concentration resulted from the blood volume expansion during the exercise in water.

  1. Filter Characteristics Influencing Circulating Tumor Cell Enrichment from Whole Blood

    PubMed Central

    Beck, Markus; Terstappen, Leon W. M. M.

    2013-01-01

    A variety of filters assays have been described to enrich circulating tumor cells (CTC) based on differences in physical characteristics of blood cells and CTC. In this study we evaluate different filter types to derive the properties of the ideal filter for CTC enrichment. Between 0.1 and 10 mL of whole blood spiked with cells from tumor cell lines were passed through silicon nitride microsieves, polymer track-etched filters and metal TEM grids with various pore sizes. The recovery and size of 9 different culture cell lines was determined and compared to the size of EpCAM+CK+CD45−DNA+ CTC from patients with metastatic breast, colorectal and prostate cancer. The 8 µm track-etched filter and the 5 µm microsieve had the best performance on MDA-231, PC3-9 and SKBR-3 cells, enriching >80% of cells from whole blood. TEM grids had poor recovery of ∼25%. Median diameter of cell lines ranged from 10.9–19.0 µm, compared to 13.1, 10.7, and 11.0 µm for breast, prostate and colorectal CTC, respectively. The 11.4 µm COLO-320 cell line had the lowest recovery of 17%. The ideal filter for CTC enrichment is constructed of a stiff, flat material, is inert to blood cells, has at least 100,000 regularly spaced 5 µm pores for 1 ml of blood with a ≤10% porosity. While cell size is an important factor in determining recovery, other factors must be involved as well. To evaluate a filtration procedure, cell lines with a median size of 11–13 µm should be used to challenge the system. PMID:23626725

  2. Filter characteristics influencing circulating tumor cell enrichment from whole blood.

    PubMed

    Coumans, Frank A W; van Dalum, Guus; Beck, Markus; Terstappen, Leon W M M

    2013-01-01

    A variety of filters assays have been described to enrich circulating tumor cells (CTC) based on differences in physical characteristics of blood cells and CTC. In this study we evaluate different filter types to derive the properties of the ideal filter for CTC enrichment. Between 0.1 and 10 mL of whole blood spiked with cells from tumor cell lines were passed through silicon nitride microsieves, polymer track-etched filters and metal TEM grids with various pore sizes. The recovery and size of 9 different culture cell lines was determined and compared to the size of EpCAM+CK+CD45-DNA+ CTC from patients with metastatic breast, colorectal and prostate cancer. The 8 µm track-etched filter and the 5 µm microsieve had the best performance on MDA-231, PC3-9 and SKBR-3 cells, enriching >80% of cells from whole blood. TEM grids had poor recovery of ∼25%. Median diameter of cell lines ranged from 10.9-19.0 µm, compared to 13.1, 10.7, and 11.0 µm for breast, prostate and colorectal CTC, respectively. The 11.4 µm COLO-320 cell line had the lowest recovery of 17%. The ideal filter for CTC enrichment is constructed of a stiff, flat material, is inert to blood cells, has at least 100,000 regularly spaced 5 µm pores for 1 ml of blood with a ≤10% porosity. While cell size is an important factor in determining recovery, other factors must be involved as well. To evaluate a filtration procedure, cell lines with a median size of 11-13 µm should be used to challenge the system.

  3. Filtration parameters influencing circulating tumor cell enrichment from whole blood.

    PubMed

    Coumans, Frank A W; van Dalum, Guus; Beck, Markus; Terstappen, Leon W M M

    2013-01-01

    Filtration can achieve circulating tumor cell (CTC) enrichment from blood. Key parameters such as flow-rate, applied pressure, and fixation, vary largely between assays and their influence is not well understood. Here, we used a filtration system, to monitor these parameters and determine their relationships. Whole blood, or its components, with and without spiked tumor cells were filtered through track-etched filters. We characterize cells passing through filter pores by their apparent viscosity; the viscosity of a fluid that would pass with the same flow. We measured a ratio of 5·10(4)∶10(2)∶1 for the apparent viscosities of 15 µm diameter MDA-231 cells, 10 µm white cells and 90 fl red cells passing through a 5 µm pore. Fixation increases the pressure needed to pass cells through 8 µm pores 25-fold and halves the recovery of spiked tumor cells. Filtration should be performed on unfixed samples at a pressure of ∼10 mbar for a 1 cm(2) track-etched filter with 5 µm pores. At this pressure MDA-231 cells move through the filter in 1 hour. If fixation is needed for sample preservation, a gentle fixative should be selected. The difference in apparent viscosity between CTC and blood cells is key in optimizing recovery of CTC.

  4. Filtration Parameters Influencing Circulating Tumor Cell Enrichment from Whole Blood

    PubMed Central

    Beck, Markus; Terstappen, Leon W. M. M.

    2013-01-01

    Filtration can achieve circulating tumor cell (CTC) enrichment from blood. Key parameters such as flow-rate, applied pressure, and fixation, vary largely between assays and their influence is not well understood. Here, we used a filtration system, to monitor these parameters and determine their relationships. Whole blood, or its components, with and without spiked tumor cells were filtered through track-etched filters. We characterize cells passing through filter pores by their apparent viscosity; the viscosity of a fluid that would pass with the same flow. We measured a ratio of 5·104∶102∶1 for the apparent viscosities of 15 µm diameter MDA-231 cells, 10 µm white cells and 90 fl red cells passing through a 5 µm pore. Fixation increases the pressure needed to pass cells through 8 µm pores 25-fold and halves the recovery of spiked tumor cells. Filtration should be performed on unfixed samples at a pressure of ∼10 mbar for a 1 cm2 track-etched filter with 5 µm pores. At this pressure MDA-231 cells move through the filter in 1 hour. If fixation is needed for sample preservation, a gentle fixative should be selected. The difference in apparent viscosity between CTC and blood cells is key in optimizing recovery of CTC. PMID:23658615

  5. [The Contribution of Vascular Capacity and Blood Volume to Maintain Stable Blood Circulation during General Anesthesia].

    PubMed

    Shigemi, Kenji

    2016-05-01

    To maintain proper cardiac preload is one of the most effective procedures for the systemic circulation remaining stable. In particular, the balance between vascular capacity and total blood volume must be maintained within appropriate range by the administration of fluids, blood and/or vasoactive drugs with mean circulatory filling pressure (Pmcf), central venous pressure (CVP) or stroke volume variation (SVV). End-diastolic left ventricular volume (Ved) is theoretically the best index of cardiac preload; however, without transesophageal echocardbalanceiogram we cannot directly monitor Ved during anesthesia. The infused fluid volume remaining in intravascular space, the vascular capacity controlled by autonomic nervous system and/or vasoactive agents, and the unstressed blood volume properly mobilized to excess blood volume are the crucial factors to maintain cardiac output The knowledge of vascular physiology contribute the decision making to manipulate such factors to control blood circulation during general anesthesia. For example, CVP is usually maintained in the narrow range and seems to be stable; however, it must be changed just after the circulatory disturbances, such as acute bleeding, blood transfusion, and fluid infusion, and followed by gradual returning to initial value, because of the solid mechanism to preserve cardiac output

  6. [The discovery of blood circulation: revolution or revision?].

    PubMed

    Crignon, Claire

    2011-01-01

    The discovery of the principle of blood circulation by William Harvey is generally considered as one of the major events of the "scientific revolution" of the 17th century. This paper reconsiders the question by taking in account the way Harvey's discovery was discussed by some contemporary philosophers and physicians, in particular Fontenelle, who insisted on the necessity of redefining methods and principles of medical knowledge, basing themselves on the revival of anatomy and physiology, and of its consequences on the way it permits to think about the human nature. This return allows us to consider the opportunity of substituting the kuhnian scheme of "structure of scientific revolutions" for the bachelardian concept of "refonte".

  7. [Evaluation of the hypomagnetic environment effects on capillary blood circulation, blood pressure and heart rate].

    PubMed

    Gurfinkel, Iu I; Vasin, A L; Matveeva, T A; Sasonko, M L

    2014-01-01

    Impact of attenuated magnetic field (MF) on human health is a hard-core issue of present-day cosmonautics. A series of experiments with animals exposed in attenuated MF revealed violent disorders in cardiovascular system development. Purpose of the work was to study effects of the hypomagnetic environment (HME) on capillary blood circulation, blood pressure (BP) and heart rate (HR) in normal people. Participants (n = 34) were 24 men and 10 women free from cardiovascular symptoms. Mean age was 43.3 +/- 15.4 years. Thirteen participants, i.e. 8 men and 5 women, were randomly selected for a repeated investigation in the usual conditions (imaginary exposure); mean age in the group made up 47.9 +/- 18 years. Cardiac rhythm and heart rate were recorded using cardiac monitor Astrocard (Russia). BP was measured with the help of automatic blood pressure monitor Tonocard (Russia). Capillary circulation was determined using a digital capillaroscope (Russia) with high-speed CMOS-camera (100 frames/s). Time of HME exposure was 60 min. It was demonstrated that in healthy people free from cardiovascular symptoms HME increases capillary circulation rate by 22.4% as compared with records made under the usual conditions. There was a reliable HR reduction by the end of HME exposure with reference to the measurements taken at the onset. At the end of exposure, diastolic BP dropped considerably relative to mid-exposure values and systolic BP, on the contrary, made a significant rise.

  8. [Acupuncture theory of promoting blood circulation and removing stasis and its clinical application].

    PubMed

    Yao, Jun

    2015-04-01

    The effects and methods of acupuncture on promoting blood circulation and removing stasis and its importance for modern clinical acupuncture are explored and explained. The acupuncture theory of promoting blood circulation and removing stasis in Internal Canon of Yellow Emperor and the ancient medical scholars' knowledge of acupuncture for promoting blood circulation and removing stasis are traced, and then the principles and characteristics of acupuncture for promoting blood circulation and removing stasis are explored and summarized. The methods and common tools of prompting blood circulation and removing stasis of modern clinical acupuncture are summed up as well. It is considered that the treatment principles and methods of acupuncture for prompting blood and removing stasis deserve to be paid attention to and applied by all departments of clinical acupuncture.

  9. Changes in circulating blood volume following isoflurane or sevoflurane anesthesia.

    PubMed

    Hamada, H; Takaori, M; Kimura, K; Fukui, A; Fujita, Y

    1993-07-01

    Changes of circulating blood volume (CB volume) measured by the dual indicator dilution method were observed in 33 chronically instrumented mongrel dogs following either alpha-chloralose-urethane (C group), additive isoflurane (I group) or sevoflurane anesthesia (S group). These anesthetic groups were each divided into two subgroups with regard to respiratory care, namely Cp, Ip and Sp for those with intermittent positive pressure ventilation (six animals per subgroups), and Cs, Is and Ss for those with spontaneous breathing (five animals per subgroups). The CB volume under positive pressure ventilation remained unchanged in the Ip and Sp groups at both 0.5 and 1.0 MAC, and in the Cp group. The CB volume remained essentially unchanged in the Cs and Is groups at both 0.5 or 1.0 MAC, but the plasma volume tended to increase slightly in the Is group at 1.0 MAC. In the Ss group under spontaneous breathing, however, the CB volume increased from 84.4 +/- 7.0 to 91.4 +/- 7.7 at 0.5 MAC, and to 91.4 +/- 10.2 ml.kg(-1) at 1.0 MAC (0.01 < P < 0.05). These increases were caused by an increase in the plasma volume. The above data suggests that a concomitant increase in the venous pressure associated with an increase in the intrathoracic pressure produced by positive pressure ventilation would attenuate changes in the CB volume during sevoflurane anesthesia. PMID:15278818

  10. Speckle-correlation analysis of the microcapillary blood circulation in nail bed

    SciTech Connect

    Vilenskii, M A; Agafonov, D N; Zimnyakov, D A; Tuchin, Valerii V; Zdrazhevskii, R A

    2011-04-30

    We present the results of the experimental studies of the possibility of monitoring the blood microcirculation in human finger nail bed with application of speckle-correlation analysis, based on estimating the contrast of time-averaged dynamic speckles. The hemodynamics at normal blood circulation and under conditions of partially suppressed blood circulation is analysed. A microscopic analysis is performed to visualise the structural changes in capillaries that are caused by suppressing blood circulation. The problems and prospects of speckle-correlation monitoring of the nail bed microhemodynamics under laboratory and clinical conditions are discussed. (optical technologies in biophysics and medicine)

  11. Therapeutic possibilities of techniques of extracorporeal blood circulation in oncology.

    PubMed

    Ricci, Sante Basso

    2012-01-01

    Malignant tumors in an advanced phase of diffusion have a very poor prognosis. However, there are conditions in the body which may impede, even if only partially, further spread of the disease. In addition to currently available treatments, other favorable conditions can help to improve the prognosis, even if only relatively, such as the presence of inhibitors of metalloproteinases, antiangiogenic factors, the absence of particular proteins that favor tumor development, and the possibility of positively activating the immune system. The authors believe that in cases where such conditions are concurrent, the addition of a new favorable condition could be very useful. On the other hand, cases of total spontaneous regression of malignancies, even if in metastatic diffusion, are well known. It was recently emphasized that the spread of metastasis of renal cell carcinoma, arising in patients on hemodialysis for a long time, is considerably reduced at the post-mortem examination compared to patients with renal cell carcinoma and not on hemodialysis. This may suggest a positive effect exerted by the dialytic membrane on metastatic spread. The authors hypothesize that extracorporeal circulation of the blood, used mainly for cardiovascular interventions and hemodialysis, could be used by applying filters suitable for cancer treatments, similar to those used in hemodialysis, even if without accomplishing the hemodialytic function, provided there are no objections to their biocompatibility. In this case, the block of metastatic cells could lead to a relative increase in the cellular elements of the immune system (NK cells and T lymphocytes) compared to cancer cells, or rather to the relative reduction in the number of cancer cells compared to NK cells and T lymphocytes. Such a block would prevent any feedback reactions, so frequent and damaging to the prognosis when using overall medical stimulation for the immune system.

  12. [PULMONARY COMPLICATIONS IN CHILDREN, OPERATED ON FOR INBORN HEART FAILURES IN THE ARTIFICIAL BLOOD CIRCULATION ENVIRONMENT].

    PubMed

    Moshkivska, L V; Nastenko, E A; Golovenko, O S; Lazoryshynets, V V

    2015-11-01

    The risk factors of pulmonary complications occurrence were analyzed in children, operated on for inborn heart failures in atrificial blood circulation environment. Pulmonary complications rate and the risk factors of their occurrence were analyzed.

  13. Relationship Not Found Between Blood and Urine Concentrations and Body Mass Index in Humans With Apparently Adequate Boron Status.

    PubMed

    Koc, Fulya; Aysan, Erhan; Hasbahceci, Mustafa; Arpaci, Beyza; Gecer, Salih; Demirci, Selami; Sahin, Fikrettin

    2016-06-01

    The impact of boron on the development of obesity remains controversial in the analysis of experimental and clinical data. The objective of this study was to investigate the relationship between blood and urine boron concentrations and obesity in normal, overweight, obese, and morbidly obese subjects in different age groups. A total of 105 subjects were categorized into 12 groups based on body mass index and three different age levels: as young adult (18 to 34 years old), adult (35 to 54 years old), and older adult (greater than 55 years old). Age, gender, body mass index, and blood and urine boron concentrations were recorded for each subject. There were 50 women and 55 men, with a mean age of 44.63 ± 17.9 years. Blood and urine boron concentrations were similar among the groups (p = 0.510 and p = 0.228, respectively). However, a positive correlation between age and blood boron concentration (p = 0.001) was detected in contrast to the presence of a negative correlation between age and urine boron concentration (p = 0.027). Multiple linear regression analysis showed that there was no significant relationship between gender, age, and quantitative values of body mass index for each subject, and blood and urine boron concentrations. Although the relationship between boron and obesity has not been confirmed, changes of blood and urine boron concentrations with age may have some physiologic sequences to cause obesity.

  14. Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents.

    PubMed

    Xiao, Wangchuan; Lin, Jiang; Li, Mingli; Ma, Yongjie; Chen, Yuxin; Zhang, Chunfu; Li, Dan; Gu, Hongchen

    2012-01-01

    Long circulation time is critical for blood pool contrast agents used in high-resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long-circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3-(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N-(3-dimethylaminopropyl)-N'-ethylcarbo-diimide hydrochloride/N-hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time.

  15. Analysis of the adequate size of a cord blood bank and comparison of HLA haplotype distributions between four populations.

    PubMed

    Haimila, Katri; Penttilä, Antti; Arvola, Anne; Auvinen, Marja-Kaisa; Korhonen, Matti

    2013-02-01

    The number of units and especially the number of different HLA haplotypes present in a cord blood (CB) bank is a crucial determinant of its usefulness. We generated data relevant to the development of our national CB in Finland. The HLA haplotype distribution was examined between specific populations. We developed graphical ways of data presentation that enable easy visualization of differences. First, we estimated the optimal size of a CB bank for Finland and found that approximately 1700 units are needed to provide a 5/6 HLA-matched donor for 80% of Finnish patients. Secondly, we evaluated HLA haplotype distributions between four locations, Finland, Japan, Sweden and Belgium. Our results showed that the Japanese Tokyo Cord Blood Bank differs in both the frequency and distribution of haplotypes from the European banks. The European banks (Finnish Cord Blood Registry, The Swedish National Cord Blood Bank, and Marrow Donor Program-Belgium) have similar frequencies of common haplotypes, but 26% of the haplotypes in the Finnish CB bank are unique, which justifies the existence of a national bank. The tendency to a homogenous HLA haplotype distribution in banks underlines the need for targeting recruitment at the poorly represented minority populations.

  16. The Effect of Pulsatile Versus Nonpulsatile Blood Flow on Viscoelasticity and Red Blood Cell Aggregation in Extracorporeal Circulation

    PubMed Central

    Ahn, Chi Bum; Kang, Yang Jun; Kim, Myoung Gon; Yang, Sung; Lim, Choon Hak; Son, Ho Sung; Kim, Ji Sung; Lee, So Young; Son, Kuk Hui; Sun, Kyung

    2016-01-01

    Background Extracorporeal circulation (ECC) can induce alterations in blood viscoelasticity and cause red blood cell (RBC) aggregation. In this study, the authors evaluated the effects of pump flow pulsatility on blood viscoelasticity and RBC aggregation. Methods Mongrel dogs were randomly assigned to two groups: a nonpulsatile pump group (n=6) or a pulsatile pump group (n=6). After ECC was started at a pump flow rate of 80 mL/kg/min, cardiac fibrillation was induced. Blood sampling was performed before and at 1, 2, and 3 hours after ECC commencement. To eliminate bias induced by hematocrit and plasma, all blood samples were adjusted to a hematocrit of 45% using baseline plasma. Blood viscoelasticity, plasma viscosity, hematocrit, arterial blood gas analysis, central venous O2 saturation, and lactate were measured. Results The blood viscosity and aggregation index decreased abruptly 1 hour after ECC and then remained low during ECC in both groups, but blood elasticity did not change during ECC. Blood viscosity, blood elasticity, plasma viscosity, and the aggregation index were not significantly different in the groups at any time. Hematocrit decreased abruptly 1 hour after ECC in both groups due to dilution by the priming solution used. Conclusion After ECC, blood viscoelasticity and RBC aggregation were not different in the pulsatile and nonpulsatile groups in the adult dog model. Furthermore, pulsatile flow did not have a more harmful effect on blood viscoelasticity or RBC aggregation than nonpulsatile flow. PMID:27298790

  17. Autoregulation of cerebral blood circulation under orthostatic tests

    NASA Technical Reports Server (NTRS)

    Gayevyy, M. D.; Maltsev, V. G.; Pogorelyy, V. E.

    1980-01-01

    Autoregulation of cerebral blood flow (ACBF) under orthostatic tests (OT) was estimated in acute experiments on rabbits and cats under local anesthesia according to changes of perfusion pressure (PP) in carotid arteries, cerebral blood flow, pressure in the venous system of the brain, and resistance of cerebral vessels. The OT were conducted by turning a special table with the animal fastened to it from a horizontal to a vertical (head up or head down) position at 40 to 80 deg. In most experiments ACBF correlated with the changes of PP. Different variations of ACBF and its possible mechanisms are discussed.

  18. [Intersystem interaction of the respiration and blood circulation].

    PubMed

    Donina, Zh A

    2011-01-01

    The review includes modern data about the functional interaction of respiratory and bloods circulatory systems in different conditions. The special attention is given to adaptive changes of respiratory and haemodynamic indices in extreme conditions. Based on the own researches physiological parallels between intersystem correlation of respiratory biomechanics and haemodynamics in the conditions of normal gravitation and weightlessness are drawn.

  19. Role of nitric oxide in development of centralization of blood circulation upon experimental hemorrhagic shock.

    PubMed

    Remizova, M I; Gerbut, K A

    2014-05-01

    Effects of a NO donor L-arginine and a non-selective NO-synthase inhibitor N(G)-nitro-Larginine methyl ester on BP, microcirculation, acid-base balance, and gas content of blood were examined on rat model of hemorrhagic shock; the substances were administered without infusion media before blood loss. Bloodletting was stopped after manifestation of marked microcirculation disorders. Inhibition of NO synthesis in response to blood loss resulted in pronounced centralization of blood circulation with microcirculation disturbances, which was accompanied by metabolic changes aggravating hemorrhagic shock. Administration of NO donor reduced the degree of circulation centralization, maintained vasodilatatory vascular tone and perfusion of vital organs, improved animal resistance to blood loss, and prolonged their lifespan. Enhanced NO generation after administration of NO donor promoted longer microcirculation maintenance, which suggests that the so-called basal level of NO is essential at early stages of hemorrhagic shock.

  20. [Myelopathies in impairment of extravertebral venous blood circulation].

    PubMed

    Tsuladze, I I; Dreval', O N; Kornienko, V N

    2009-01-01

    Development of myelopathies of venous genesis is based on venous hypertension inside vertebral canal which was initially described by J. Aboulker. According to anatomical and functional features of epidural venous system, two factors contribute in development of venous congestion: decreased outflow and increased inflow. Clinical manifestation is presented by spastic movement disorders. Morphological study performed in 18 cadavers allowed to discover so called 'narrow areas' which cause impaired circulation through large feeders of caval veins, which can be discovered by selective phlebography. Main phlebographic features include stenosis, compression, atresia, thrombosis and retrograde flow towards epidural venous plexus. We examined 58 patients with spastic para- and tetraparesis of unknown nature. Phlebographic signs of venous dyscirculation were revealed in 34 cases. 28 surgical operations were performed: 24 on feeders of vena cava superior and 4 on feeders of vena cava inferior. In 18 cases we obtained satisfactory results. This investigation should be continued.

  1. Circulating Fatty Acid Synthase in pregnant women: Relationship to blood pressure, maternal metabolism and newborn parameters

    PubMed Central

    Carreras-Badosa, Gemma; Prats-Puig, Anna; Puig, Teresa; Vázquez-Ruíz, Montserrat; Bruel, Monserrat; Mendoza, Ericka; de Zegher, Francis; Ibáñez, Lourdes; López-Bermejo, Abel; Bassols, Judit

    2016-01-01

    The enzyme FASN (fatty acid synthase) is potentially related with hypertension and metabolic dysfunction. FASN is highly expressed in the human placenta. We aimed to investigate the relationship circulating FASN has with blood pressure, maternal metabolism and newborn parameters in healthy pregnant women. Circulating FASN was assessed in 115 asymptomatic pregnant women in the second trimester of gestation along with C-peptide, fasting glucose and insulin, post-load glucose lipids, HMW-adiponectin and blood pressure (the latter was assessed in each trimester of gestation). At birth, newborns and placentas were weighed. FASN expression was also able to be assessed in 80 placentas. Higher circulating FASN was associated with lower systolic blood pressure (SBP), with a more favourable metabolic phenotype (lower fasting glucose and insulin, post load glucose, HbAc1, HOMA-IR and C-peptide), and with lower placental and birth weight (all p < 0.05 to p < 0.001). Placental FASN expression related positively to circulating FASN (p < 0.005) and negatively to placental weight (p < 0.05). Our observations suggest a physiological role of placental FASN in human pregnancy. Future studies will clarify whether circulating FASN of placental origin does actually regulate placental and fetal growth, and (thereby) has a favourable influence on the pregnant mother’s insulin sensitivity and blood pressure. PMID:27090298

  2. Blood Circulation Laboratory Investigations with Video Are Less Investigative than Instructional Blood Circulation Laboratories with Live Organisms

    ERIC Educational Resources Information Center

    Hoover, Mildred A.; Pelaez, Nancy J.

    2008-01-01

    Live organisms versus digital video of the organisms were used to challenge students' naive ideas and misconceptions about blood, the heart, and circulatory patterns. Three faculty members taught 259 grade 10 biology students in a California high school with students from diverse ethnolinguistic groups who were divided into 5 classes using…

  3. Daily variation in radiosensitivity of circulating blood cells and bone marrow cell density in mice

    SciTech Connect

    Tabatabai, R.N.

    1984-01-01

    Mice on a 12/12 light/dark cycle were bled during a twenty-four hour period each week for eight weeks to establish daily values of circulating blood cells. No significant daily variation was found in total red blood cells, hematocrit, or percentage of reticulocytes. A significant (P < 0.001) daily variation was found in total white blood cells, with the minimum occurring at 8 PM and the maximum occurring during the daylight hours from 8 a.m. to 2 p.m. Mice were then exposed to 0 R, 20 R, 50 R, or 100 R of x-radiation to determine what dose significantly reduces the total white cell count in circulating blood. It was found that 100 R significantly (P < .05) reduces the total white cell count over a four week period post-exposure. To determine if circulating blood cells and bone marrow cells show a diurnal radiosensitivity, mice were exposed to 100 R or 200 R of x-radiation at noon or midnight. Hematocrits, reticulocyte and white blood cell counts, daily white blood cell rhythm, and bone marrow cell density indicate that these mice were more radiosensitive at night.

  4. [Oxygen-transporting function of the blood circulation system in sevoflurane anesthesia during myocardial revascularization under extracorporeal circulation].

    PubMed

    Skopets, A A; Lomivorotov, V V; Karakhalis, N B; Makarov, A A; Duman'ian, E S; Lomivorotova, L V

    2009-01-01

    The purpose of the study was to evaluate the efficiency of oxygen-transporting function of the circulatory system under sevoflurane anesthesia during myocardial revascularization operations under extracorporeal circulation. Twenty-five patients with coronary heart disease were examined. Mean blood pressure, heart rate, cardiac index, total peripheral vascular resistance index, pulmonary pressure, pulmonary wedge pressure, and central venous pressure were measured. Arterial and mixed venous blood oxygen levels, oxygen delivery and consumption index, arteriovenous oxygen difference, and glucose and lactate concentrations were calculated. The study has demonstrated that sevoflurane is an effective and safe anesthetic for myocardial revascularization operations in patients with coronary heart disease. The use of sevoflurane contributes to steady-state oxygen-transporting function of the circulatory system at all surgical stages.

  5. An ethanol extract of Ramulus mori improves blood circulation by inhibiting platelet aggregation.

    PubMed

    Lee, Jiyun; Kwon, Gayeung; Park, Jieun; Kim, Jeong-Keun; Choe, Soo Young; Seo, Yoonhee; Lim, Young-Hee

    2016-07-01

    Inappropriate platelet aggregation can cause blood coagulation and thrombosis. In this study, the effect of an ethanol extract of Ramulus mori (ERM) on blood circulation was investigated. The antithrombotic activity of ERM on rat carotid arterial thrombosis was evaluated in vivo, and the effect of ERM on platelet aggregation and blood coagulation time was evaluated ex vivo. To evaluate the safety of ERM, its cytotoxicity to platelets and its effect on tail bleeding time were assessed; ERM was not toxic to rat platelets and did not prolong bleeding time. Moreover, administering ERM to rats had a significant preventive effect on carotid arterial thrombosis in vivo, and significantly inhibited adenosine diphosphate- and collagen-induced platelet aggregation ex vivo, whereas it did not prolong coagulation periods, such as prothrombin time and activated partial thromboplastin time. The results suggest that ERM is effective in improving blood circulation via antiplatelet activity rather than anticoagulation activity.

  6. Blood circulation laboratory investigations with video are less investigative than instructional blood circulation laboratories with live organisms.

    PubMed

    Hoover, Mildred A; Pelaez, Nancy J

    2008-03-01

    Live organisms versus digital video of the organisms were used to challenge students' naive ideas and misconceptions about blood, the heart, and circulatory patterns. Three faculty members taught 259 grade 10 biology students in a California high school with students from diverse ethnolinguistic groups who were divided into 5 classes using microscopes (128 students) and 5 classes using digital video (131 students) to compare blood transport among invertebrates, fish, and humans. The "What Is Happening in this Class?" (WIHIC) questionnaire was used for assessment of microscope and video groups to detect students' perception of their learning environment following these teaching interventions. The use of microscopes had a clear effect on the perception of the investigative aspects of the learning environment that was not detected with the video treatment. Findings suggest that video should not replace investigations with live organisms.

  7. Exploring the Impact of Students' Learning Approach on Collaborative Group Modeling of Blood Circulation

    ERIC Educational Resources Information Center

    Lee, Shinyoung; Kang, Eunhee; Kim, Heui-Baik

    2015-01-01

    This study aimed to explore the effect on group dynamics of statements associated with deep learning approaches (DLA) and their contribution to cognitive collaboration and model development during group modeling of blood circulation. A group was selected for an in-depth analysis of collaborative group modeling. This group constructed a model in a…

  8. Isolation of naturally occurring Campylobacter from the circulating blood of commercial market age broilers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter spp., are present in organs and tissues of broiler chickens but the dissemination route is unclear. The aim of the current study was to determine Campylobacter prevalence within circulating blood of commercial broilers. Broilers were acquired from 19 flocks originating from three com...

  9. [The issues of assessment of medical support of patients with pathology of blood circulation system].

    PubMed

    Maksimova, T M; Lushkina, N P; Ogryzko, Ye V

    2012-01-01

    The analysis of report forms No 12 "The information about number of diseases registered in patients residing in the area of medical institution supports" and No14 "The information about functioning of hospital" demonstrated that in conditions of ambulatory policlinic institutions there is no active monitoring of patients with diseases of blood circulation system. These diseases are the major causes of population mortality.

  10. [Reasonable application of traditional Chinese medicines injections promoting blood circulation and removing blood stasis in treating ischemic cerebrovascular diseases].

    PubMed

    Lv, Zhi-Guo; Xie, Yan-Ming; Li, Ming-Quan; Zhao, Jian-Jun; Wei, Xu

    2012-11-01

    Currently, there are many traditional Chinese medicine (TCM) injections for treating ischemic stroke in the market, most of them have the efficacy of promoting blood circulation and removing blood stasis, but their reasonable applications are worth consideration. From the angles of traditional Chinese medicine and modern medicine, TCM injections that are commonly used in clinics were detected for their indications and pharmacological effects, compared in terms of their characteristics of clinical application, precautions, prohibition on use, caution and adverse reactions and categorized, in order to help clinicians with reasonable application of TCM injections.

  11. [Doctor Ma Kun's experience of applying tonifying kidney and promoting blood circulation treatment of anovulatory infertility].

    PubMed

    Shan, Jing

    2014-02-01

    With the ascending attack rate of anovulatory infertility year by year, people also began to pay attention to its treat methods. According to Doctor Ma Kun,who are engaged in clinical work about the treatment for anovulatory infertility, kidney deficiency is the basic pathogenesis and blood stasis is an important factor that has been through. Flexible use of tonifying the kidney and promoting blood circulation treatment of anovulatory infertility in clinic, has achieved remarkable curative effect. Director Ma adjusts menstruation by the different periods, and regulates both patients' negative emotions and sleep quality. Through years of clinical experience accumulation, Director Ma gradually formes special treatment of anovulatory infertility by flexibly using of tonifying the kidney and promoting blood circulation individually.

  12. [Endothelial glycocalyx of blood circulation. II. Biological functions, state at norm and pathology, bioengineering application].

    PubMed

    Maksimenko, A V; Turashev, A D

    2014-01-01

    In normal state, a complex multicomponent system called glycocalyx is present on the surface of endothelial vascular system. Due to complexity of its composition and location on the border between vessel wall and blood circulation, glycocalyx participates in a number of functions supporting the metabolism of the vascular wall. In pathological conditions undergo complete or partial loss of this structure, which leads to inconsistencies in the vascular wall and change its functions. The functions of endothelial glycocalyx are its involvement in the regulation of vascular permeability, transduction and transformation by the shear stress of blood flow on endothelium, the molecular regulation of glycocalyx microenvironment and its interaction with circulating blood cells. Also briefly be considered participation of glycocalyx in the implementation of cardiovascular diseases, their correction, bioengineering application of glycocalyx and its components.

  13. A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

    PubMed

    Garcia-Canadilla, Patricia; Rudenick, Paula A; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijnens, Bart H; Bijens, Bart H

    2014-06-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling

  14. A Computational Model of the Fetal Circulation to Quantify Blood Redistribution in Intrauterine Growth Restriction

    PubMed Central

    Garcia-Canadilla, Patricia; Rudenick, Paula A.; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijens, Bart H.

    2014-01-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling

  15. Morphological and functional characterization of leech circulating blood cells: role in immunity and neural repair.

    PubMed

    Boidin-Wichlacz, Céline; Vergote, David; Slomianny, Christian; Jouy, Nathalie; Salzet, Michel; Tasiemski, Aurélie

    2012-05-01

    Unlike most invertebrates, annelids possess a closed vascular system distinct from the coelomic liquid. The morphology and the function of leech blood cells are reported here. We have demonstrated the presence of a unique cell type which participates in various immune processes. In contrast to the mammalian spinal cord, the leech CNS is able to regenerate and restore function after injury. The close contact of the blood with the nerve cord also led us to explore the participation of blood in neural repair. Our data evidenced that, in addition to exerting peripheral immune functions, leech blood optimizes CNS neural repair through the release of neurotrophic substances. Circulating blood cells also appeared able to infiltrate the injured CNS where, in conjunction with microglia, they limit the formation of a scar. In mammals, CNS injury leads to the generation of a glial scar that blocks the mechanism of regeneration by preventing axonal regrowth. The results presented here constitute the first description of neuroimmune functions of invertebrate blood cells. Understanding the basic function of the peripheral circulating cells and their interactions with lesioned CNS in the leech would allow us to acquire insights into the complexity of the neuroimmune response of the injured mammalian brain. PMID:22159559

  16. Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin.

    PubMed

    Evjen, Tove J; Hagtvet, Eirik; Nilssen, Esben A; Brandl, Martin; Fossheim, Sigrid L

    2011-07-17

    Ultrasound sensitive (sonosensitive) liposomes represent a drug delivery system designed for releasing a drug load upon exposure to ultrasound (US). Inclusion of dioleoylphosphatidylethanolamine (DOPE) in liposome membranes was previously shown to induce sonosensitivity. Long blood circulation time of the liposomal drug is required for high tumour uptake and efficient US-mediated drug delivery. In this study, blood pharmacokinetics of DOPE-based liposomal doxorubicin (DXR) were evaluated in non-tumoured mice. A markedly faster blood clearance of DXR was observed for DOPE-rich liposomes compared to Caelyx® (standard liposomal DXR). Subsequently, liposome membrane composition was altered to improve drug retention in the bloodstream, whilst maintaining sonosensitivity. Formulations with reduced blood clearance of DXR were obtained by reducing the content of DOPE from 62 to 32 or 25 mol%. These formulations showed long blood circulation time, as approximately 20% of the administered DXR dose was present in the bloodstream 24 h after intravenous injection. The reduction in liposomal DOPE content did not significantly reduce US-mediated DXR release in vitro, indicating that DOPE is a potent modulator of sonosensitivity. The novel liposome formulations, containing moderate amounts of DOPE, displayed similar blood pharmacokinetic profiles as standard liposomal DXR, but a markedly improved sonosensitivity.

  17. Circulating Blood Monocyte Subclasses and Lipid-Laden Adipose Tissue Macrophages in Human Obesity

    PubMed Central

    Pecht, Tal; Haim, Yulia; Bashan, Nava; Shapiro, Hagit; Harman-Boehm, Ilana; Kirshtein, Boris; Clément, Karine; Shai, Iris; Rudich, Assaf

    2016-01-01

    Background Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM) are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient. Methods We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM) lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65) undergoing elective abdominal surgery. Results Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,p<0.05) and ATM lipid content (r = 0.303,p<0.05). Among patients with BMI≥25Kg/m2, linear regression models adjusted for age, sex or BMI revealed that NCM independently associate with ATM lipid content, particularly in men. Conclusions Collectively, although circulating blood NCM are unlikely direct functional precursor cells for adipose tissue foam cells, their increased percentage in the circulation may clinically reflect higher lipid content in visceral ATMs. PMID:27442250

  18. Peripheral circulation.

    PubMed

    Laughlin, M Harold; Davis, Michael J; Secher, Niels H; van Lieshout, Johannes J; Arce-Esquivel, Arturo A; Simmons, Grant H; Bender, Shawn B; Padilla, Jaume; Bache, Robert J; Merkus, Daphne; Duncker, Dirk J

    2012-01-01

    Blood flow (BF) increases with increasing exercise intensity in skeletal, respiratory, and cardiac muscle. In humans during maximal exercise intensities, 85% to 90% of total cardiac output is distributed to skeletal and cardiac muscle. During exercise BF increases modestly and heterogeneously to brain and decreases in gastrointestinal, reproductive, and renal tissues and shows little to no change in skin. If the duration of exercise is sufficient to increase body/core temperature, skin BF is also increased in humans. Because blood pressure changes little during exercise, changes in distribution of BF with incremental exercise result from changes in vascular conductance. These changes in distribution of BF throughout the body contribute to decreases in mixed venous oxygen content, serve to supply adequate oxygen to the active skeletal muscles, and support metabolism of other tissues while maintaining homeostasis. This review discusses the response of the peripheral circulation of humans to acute and chronic dynamic exercise and mechanisms responsible for these responses. This is accomplished in the context of leading the reader on a tour through the peripheral circulation during dynamic exercise. During this tour, we consider what is known about how each vascular bed controls BF during exercise and how these control mechanisms are modified by chronic physical activity/exercise training. The tour ends by comparing responses of the systemic circulation to those of the pulmonary circulation relative to the effects of exercise on the regional distribution of BF and mechanisms responsible for control of resistance/conductance in the systemic and pulmonary circulations.

  19. Mechanisms and pathways for the clearance of bacteria from blood circulation in health and disease.

    PubMed

    Minasyan, Hayk

    2016-06-01

    Available data do not support the concept that leukocytes engulf and kill bacteria in the bloodstream. Leukocytes cannot recognize or engulf bacteria in flowing blood; therefore, phagocytosis is impossible in the bloodstream and occurs instead outside of the bloodstream in the body tissues. Erythrocytes capture bacteria in the circulation using an electric charge and kill them using oxidation. The dead bacteria are then disintegrated and digested by the reticuloendothelial system (RES), particularly in the liver and the spleen.

  20. Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics.

    PubMed

    Warkiani, Majid Ebrahimi; Khoo, Bee Luan; Wu, Lidan; Tay, Andy Kah Ping; Bhagat, Ali Asgar S; Han, Jongyoon; Lim, Chwee Teck

    2016-01-01

    Circulating tumor cells (CTCs) are rare cancer cells that are shed from primary or metastatic tumors into the peripheral blood circulation. Phenotypic and genetic characterization of these rare cells can provide important information to guide cancer staging and treatment, and thus further research into their characteristics and properties is an area of considerable interest. In this protocol, we describe detailed procedures for the production and use of a label-free spiral microfluidic device to allow size-based isolation of viable CTCs using hydrodynamic forces that are present in curvilinear microchannels. This spiral system enables us to achieve ≥ 85% recovery of spiked cells across multiple cancer cell lines and 99.99% depletion of white blood cells in whole blood. The described spiral microfluidic devices can be produced at an extremely low cost using standard microfabrication and soft lithography techniques (2-3 d), and they can be operated using two syringe pumps for lysed blood samples (7.5 ml in 12.5 min for a three-layered multiplexed chip). The fast processing time and the ability to collect CTCs from a large patient blood volume allows this technique to be used experimentally in a broad range of potential genomic and transcriptomic applications. PMID:26678083

  1. Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats.

    PubMed

    Takeuchi, Takashi; Kitagawa, Hiroshi; Harada, Etsumori

    2004-05-01

    Using adult rats, the characteristic transporting system for lactoferrin (LF) from intestinal lumen into the blood circulation was investigated. The rats were randomly divided into two groups, a non-collected thoracic lymph (NC) group and a collected thoracic lymph (LC) group. Peripheral blood and thoracic lymph were collected from a jugular vein and a thoracic lymph duct, respectively, under anaesthesia. Bovine LF (bLF) was infused into the duodenal lumen by needle over a 1-min period at a dose of 1 g kg(-1). The transported bLF in the plasma and lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent assay (ELISA). Morphological investigation was also carried out in the intestine, lymph node, and liver. Following intraduodenal administration of bLF, the transported bLF in the NC group was detected in the plasma, and reached a peak value at 2 h. Furthermore, the bLF concentration in the thoracic duct lymph fluid in the LC group increased significantly, and peaked 2 h after the administration. In addition, bLF was not detected in the plasma of the LC group. Immunohistochemical analysis clearly showed anti-bLF positive particles in the epithelial cells of the apical villi. The striated border and baso-lateral membrane were also bLF positive. These results suggest that intraduodenally infused bLF is transported into the blood circulation via the lymphatic pathway, not via portal circulation in adult rats.

  2. Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance.

    PubMed

    Rao, Lang; Bu, Lin-Lin; Xu, Jun-Hua; Cai, Bo; Yu, Guang-Tao; Yu, Xiaolei; He, Zhaobo; Huang, Qinqin; Li, Andrew; Guo, Shi-Shang; Zhang, Wen-Feng; Liu, Wei; Sun, Zhi-Jun; Wang, Hao; Wang, Tza-Huei; Zhao, Xing-Zhong

    2015-12-01

    For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as "accelerated blood clearance (ABC)" where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe(3)O(4) nanoparticles (Fe(3)O(4) @RBC NPs) rely on CD47, which is a "don't eat me" marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-α) receptor. Fe(3)O(4) @RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe(3)O(4) @RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance. PMID:26488923

  3. Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine.

    PubMed

    Liu, Yue; Yin, Huijun; Chen, Keji

    2013-11-01

    The development of novel and efficient antiplatelet agents that have few adverse effects and methods that improve antiplatelet resistance has long been the focus of international research on the prevention and treatment of cardiovascular and cerebrovascular diseases. Recent advances in platelet proteomics have provided a technology platform for high-quality research of platelet pathophysiology and the development of new antiplatelet drugs. The study of blood stasis syndrome (BSS) and activated blood circulation of traditional Chinese medicine (TCM) is one of the most active fields where the integration of TCM and western medicine in China has been successful. Activated blood circulation herbs (ABC herbs) of Chinese medicine are often used in the treatment of BSS. Most ABC herbs have antiplatelet and anti-atherosclerosis activity, but knowledge about their targets is lacking. Coronary heart disease (CHD), BSS, and platelet activation are closely related. By screening and identifying activated platelet proteins that are differentially expressed in BSS of CHD, platelet proteomics has helped researchers interpret the antiplatelet mechanism of action of ABC herbs and provided many potential biomarkers for BSS that could be used to evaluate the clinical curative effect of new antiplatelet drugs. In this article the progress of platelet proteomics and its advanced application for research of BSS and ABC herbs of Chinese medicine are reviewed.

  4. Mechanical blood trauma in assisted circulation: sublethal RBC damage preceding hemolysis.

    PubMed

    Olia, Salim E; Maul, Timothy M; Antaki, James F; Kameneva, Marina V

    2016-06-15

    After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory.

  5. Accurate measurement of circulating mitochondrial DNA content from human blood samples using real-time quantitative PCR.

    PubMed

    Ajaz, Saima; Czajka, Anna; Malik, Afshan

    2015-01-01

    We describe a protocol to accurately measure the amount of human mitochondrial DNA (MtDNA) in peripheral blood samples which can be modified to quantify MtDNA from other body fluids, human cells, and tissues. This protocol is based on the use of real-time quantitative PCR (qPCR) to quantify the amount of MtDNA relative to nuclear DNA (designated the Mt/N ratio). In the last decade, there have been increasing numbers of studies describing altered MtDNA or Mt/N in circulation in common nongenetic diseases where mitochondrial dysfunction may play a role (for review see Malik and Czajka, Mitochondrion 13:481-492, 2013). These studies are distinct from those looking at genetic mitochondrial disease and are attempting to identify acquired changes in circulating MtDNA content as an indicator of mitochondrial function. However, the methodology being used is not always specific and reproducible. As more than 95 % of the human mitochondrial genome is duplicated in the human nuclear genome, it is important to avoid co-amplification of nuclear pseudogenes. Furthermore, template preparation protocols can also affect the results because of the size and structural differences between the mitochondrial and nuclear genomes. Here we describe how to (1) prepare DNA from blood samples; (2) pretreat the DNA to prevent dilution bias; (3) prepare dilution standards for absolute quantification using the unique primers human mitochondrial genome forward primer (hMitoF3) and human mitochondrial genome reverse primer(hMitoR3) for the mitochondrial genome, and human nuclear genome forward primer (hB2MF1) and human nuclear genome reverse primer (hB2MR1) primers for the human nuclear genome; (4) carry out qPCR for either relative or absolute quantification from test samples; (5) analyze qPCR data; and (6) calculate the sample size to adequately power studies. The protocol presented here is suitable for high-throughput use.

  6. Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism.

    PubMed

    Yamakoshi, Yoshiki; Motegi, Sei-Ichiro; Ishikawa, Osamu

    2016-01-01

    Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer-Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method. PMID:27479094

  7. Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism

    PubMed Central

    Yamakoshi, Yoshiki

    2016-01-01

    Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer–Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method. PMID:27479094

  8. Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism.

    PubMed

    Yamakoshi, Yoshiki; Motegi, Sei-Ichiro; Ishikawa, Osamu

    2016-01-01

    Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer-Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method.

  9. Increased microRNA-34c abundance in Alzheimer's disease circulating blood plasma

    PubMed Central

    Bhatnagar, Shephali; Chertkow, Howard; Schipper, Hyman M.; Yuan, Zongfei; Shetty, Vikranth; Jenkins, Samantha; Jones, Timothy; Wang, Eugenia

    2014-01-01

    Circulating microRNAs, present either in the cellular component, peripheral blood mononuclear cells (PBMC), or in cell-free plasma, have emerged as biomarkers for age-dependent systemic, disease-associated changes in many organs. Previously, we have shown that microRNA (miR)-34a is increased in circulating PBMC of Alzheimer's disease (AD) patients. In the present study, we show that this microRNA's sister, miR-34c, exhibits even greater increase in both cellular and plasma components of AD circulating blood samples, compared to normal age-matched controls. Statistical analysis shows the accuracy of levels of miR-34c assayed by receiver operating characteristic (ROC) analysis: the area under the curve is 0.99 (p < 0.0001) and the 95% confidence level extends from 0.97 to 1. Pearson correlation between miR-34c levels and mild and moderate AD, as defined by the mini-mental state examination (MMSE), shows an r-value of −0.7, suggesting a relatively strong inverse relationship between the two parameters. These data show that plasma levels of microRNA 34c are much more prominent in AD than those of its sister, miR-34a, or than its own level in PBMC. Transfection studies show that miR-34c, as does its sister miR-34a, represses the expression of several selected genes involved in cell survival and oxidative defense pathways, such as Bcl2, SIRT1, and others, in cultured cells. Taken together, our results indicate that increased levels of miR-34c in both PBMC and plasma may reflect changes in circulating blood samples in AD patients, compared to age-matched normal controls. PMID:24550773

  10. A new torsion control mechanism induced by blood circulation in dragonfly wings.

    PubMed

    Hou, Dan; Yin, Yajun; Zhong, Zheng; Zhao, Hongxiao

    2015-02-06

    A new mechanism to generate the torque of flapping dragonfly wings is disclosed in this paper. The concept is inspired by blood circulation in insect wings. The blood flowing in veins induces Coriolis forces in the flapping wings. The Coriolis forces acting on veins are of opposite directions when blood flows in and out. The opposite Coriolis forces generate torsional moment to the wing, especially in the leading-edge part. To estimate the time-varying torque induced by the blood circulation, a simplified U-tube model is designed. A three-dimensional finite element model of the wing is developed to analyze the dynamic behaviors under this torque. The dragonfly wing is in favor of torsional deformation because the corrugated structure is of high flexural rigidity in the spanwise direction but is of low torsional rigidity in the chordwise direction. In both the downstroke and upstroke, the twist of the leading-edge part causes the sections to camber spontaneously. Such a kind of deformation is found to be of great importance to improve aerodynamic efficiency. In addition, it also compensates for the disadvantageous bending deformation caused by air pressure in flapping flight. These results are important for better understanding of the multifunctional structures of dragonfly wings and may give some inspiration to the bionics of flapping-wing micro air vehicles (FMAVs).

  11. [Clinical, structural-functional and haemodynamic correlates of cerebral venous blood circulation disturbances].

    PubMed

    Todua, F I; Verulashvili, I V; Kortushvili, M G; Gachechiladze, D G

    2006-01-01

    Difficulties of liquor circulation as a result of cerebrospinal fluid absorption and venous drainage of the entire intracranial space, in particular in the presence of venous system abnormalities in the forms of hypoplasia or aplasia of venous sinuses, play an essentiale role in cerebral venous dyscirculation. The symmetric character of hydrocephaly in chronic insufficiency of cerebral blood circulation and strong dependence of chronic cerebrovascular insufficiency on passive congestion suggest that the latter is characteristic of the blood supply system in whole. The MPI analysis of 120 patients revealed signs of cerebral ischemic lesions in 72% of cases, i.e. dilatation of liquor-containing spaces, multiple lacunar infarctions, especially in deep brain regions, diffusive changes of the periventricular white matter etc. Low indices of the blood flow increase during antiorthostatic loading, a trend towards decreasing of PI parameters and difficulty of blood flow in conditional insonation of intracranial veins in cases of "pseudotumorous syndrome" in patients with clinical signs of passive congestion. Venous dilatation of convexital brain areas and intensification of contrasting of direct sinus and vein of Galen were observed in venous infarctions.

  12. Incisions for cochlear implant flaps and superficial skin temperature. Skin temperature/blood circulation in CI flaps.

    PubMed

    Pau, Hans Wilhelm; Sievert, Uwe; Graumüller, Sylke; Wild, Ernst

    2004-01-01

    Healing and integration of a cochlear implant is largely influenced by good blood circulation in the covering skin, which, on the other hand, is closely correlated to skin temperature. Measuring superficial flap temperatures by thermography is an easy way to get some clues about the corresponding blood supply. These data should allow some implications for the design of skin flaps in cochlear implant surgery. In 15 patients thermography was carried out prior to and after cochlear implantation, using the Agema 550 Thermovision system. It was evident, that the anatomic courses of the major superficial arteries were represented by areas of increased temperature. The pattern of temperature distribution may allow some conclusions concerning site and shape of surgical incisions. From our data we concluded, that most types of incisions do not interfere too much with the arterial blood supply. However, some types like the extended retroauricular C-incision may eventually cause problems. Our data suggest, that the straight or slightly curved vertical retroauricular incision causes the least impairment of blood circulation. After surgery, directly along the incisions (and later along the scars) temperature was diminished, indicating reduced blood circulation. In our series, the thickness of the implant did not impede blood circulation significantly. So far, we could not examine patients with local circulation disorders. Probably local scars, skin atrophies, angiopathies etc. may present typical patterns of temperature distribution, which require individual design of skin flaps. Thermography is an easy method which can give impressions of local blood circulation in skin flaps. If the courses of the major arteries and their branches are respected, blood circulation within the flap should not be problematic. Thermography is likely to help designing optimal flaps in cases with impeded blood circulation e.g. by pre-existing scar formations.

  13. Hydrodynamic and label-free sorting of circulating tumor cells from whole blood

    NASA Astrophysics Data System (ADS)

    Geislinger, Thomas M.; Stamp, Melanie E. M.; Wixforth, Achim; Franke, Thomas

    2015-11-01

    We demonstrate continuous, passive, and label-free sorting of different in vitro cancer cell lines (MV3, MCF7, and HEPG2) as model systems for circulating tumor cells (CTCs) from undiluted whole blood employing the non-inertial lift effect as driving force. This purely viscous, repulsive cell-wall interaction is sensitive to cell size and deformability differences and yields highly efficient cell separation and high enrichment factors. We show that the performance of the device is robust over a large range of blood cell concentrations and flow rates as well as for the different cell lines. The collected samples usually contain more than 90% of the initially injected CTCs and exhibit average enrichment factors of more than 20 for sorting from whole blood samples.

  14. Real-time blood circulation and bleeding model for surgical training.

    PubMed

    Boisvert, Jonathan; Poirier, Guillaume; Borgeat, Louis; Godin, Guy

    2013-04-01

    Intraoperative management of bleeding is a critical skill all surgeons must possess. It is, however, very challenging to create a safe and realistic learning environment for its acquisition. In this paper, we propose a simple and efficient approach to integrate blood circulation to computerized surgical simulation systems and allow for real-time processing of punctures, ruptures, and cauterization of blood vessels. Blood pressures and flows are calculated using a system of ordinary differential equations, which can be simulated very efficiently. The equation system itself is constructed using a graph of the vessels' connectivity extracted from magnetic resonance angiograms (MRA) and completed with virtual vessels deduced from the principle of minimum work. Real-time performances of the method are assessed and results are demonstrated on ten patients who underwent a MRA before removal of a brain tumor.

  15. Effect of the technique for assisting renal blood circulation on ischemic kidney in acute cardiorenal syndrome.

    PubMed

    Hanada, Shigeru; Takewa, Yoshiaki; Mizuno, Toshihide; Tsukiya, Tomonori; Taenaka, Yoshiyuki; Tatsumi, Eisuke

    2012-06-01

    The technique for assisting renal blood circulation may be a useful therapeutic method in acute cardiorenal syndrome (ACRS), because renal ischemic dysfunction due to the reduced renal blood circulation is a powerful negative prognostic factor in ACRS. We constructed a circuit assisting renal arterial pressure and flow, and performed renal-selective blood perfusion (RSP) to the left kidney in a goat model of ACRS induced by right ventricular rapid pacing (n = 8), with the right kidney left intact as an internal control. Upon induction of ACRS, renal arterial flow (RAF), creatinine clearance (CCr), and renal oxygen consumption (RVO(2)) of the left kidney decreased to 49, 48, and 63% of the respective baseline values accompanied by a significant increase in renal vascular resistance (RVR), and similar results were observed in the right kidney. Then, RSP improved RVR and increased left RAF, CCr, and RVO(2) up to 91, 86, and 93% of baseline values, respectively, without a significant change in systemic hemodynamics. The RSP-treated kidney showed significantly higher CCr and urinary excretion of water and sodium compared to the contralateral kidney. Additional infusion of prostaglandin E(1) with RSP decreased RVR further and enabled the left RAF to increase up to 129% of the baseline value, without a significant change in systemic hemodynamic parameters. The CCr and RVO(2) did not change significantly, and urinary excretion of water and sodium showed a tendency to increase. These findings suggest that the technique for assisting renal blood circulation for both kidneys may offer a new treatment strategy for patients with ACRS.

  16. Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells.

    PubMed

    Ezura, Yoichi; Nagata, Junji; Nagao, Masashi; Hemmi, Hiroaki; Hayata, Tadayoshi; Rittling, Susan; Denhardt, David T; Noda, Masaki

    2015-01-01

    Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis.

  17. Axial PEGylation of Tin Octabutoxy Naphthalocyanine Extends Blood Circulation for Photoacoustic Vascular Imaging.

    PubMed

    Huang, Haoyuan; Wang, Depeng; Zhang, Yuzhen; Zhou, Yang; Geng, Jumin; Chitgupi, Upendra; Cook, Timothy R; Xia, Jun; Lovell, Jonathan F

    2016-07-20

    Attachment of polyethylene glycol (PEG) can prolong blood circulation of biological molecules, a useful trait for a vascular imaging agent. Here, we present a route for modifying octabutoxy naphthalocyanine (ONc) with PEG, via axial conjugation following ONc chelation with Sn(IV) chloride (Sn-ONc). Tin chelation caused ONc absorbance to shift from 860 to 930 nm. Hydroxy terminated PEG was treated with sodium and then was axially attached to the tin, generating PEG-Sn-ONc. Unlike ONc or Sn-ONc, PEG-Sn-ONc was soluble in methanol. ONc and PEG-Sn-ONc were dissolved in polysorbate solutions and administered to mice intravenously. PEG-Sn-ONc demonstrated substantially longer blood circulation time than ONc, with a 4 times longer half-life and a nearly 10 times greater area under the curve. PEG-Sn-ONc gave rise to photoacoustic contrast and could be used for noninvasive brain vessel imaging even 24 h following injection. This work demonstrates that nonmetallic naphthalocyanines can be chelated with tin, and be axially modified with PEG for enhanced circulation times for long-term vascular imaging with photoacoustic tomography.

  18. A novel liposome surface modification agent that prolongs blood circulation and retains surface ligand reactivity.

    PubMed

    Ishihara, Atsushi; Yamauchi, Masahiro; Tsuchiya, Tomoko; Mimura, Yukiteru; Tomoda, Yutaka; Katagiri, Ayato; Kamiya, Masaaki; Nemoto, Hisao; Suzawa, Toshiyuki; Yamasaki, Motoo

    2012-01-01

    Liposomes are recognized as potentially useful drug carriers but many problems preclude practical medical application. Liposomes bind with serum proteins (opsonization) and are captured by the reticuloendothelial system cells in the liver and spleen, which limits their ability to deliver drugs to other target sites. Modification of lipids with flexible, hydrophilic polymers such as poly(ethylene glycol) (PEG) to yield sterically stabilized liposomes is one approach to improve liposome blood circulation and tissue distribution properties. In this study, we examined liposomes prepared using lipids modified with a new branched oligoglycerol (BGL) moiety for steric stabilization. This novel BGL comprised 14 glycerol units (termed BGL014) connected with flexible ether linkages, resulting in a branched cascade-like structure that is highly expanded in aqueous solution. BGL014 was coupled to 1,2-distearoylphosphatidylethanolamine to yield BGL014-modified lipids. Incorporation of BGL014 into liposomes (BGL014L) resulted in long blood circulation times, despite a much thinner fixed aqueous layer thickness compared to PEG formulations. BGL014 produced a liposome surface coating that appears to function through steric inhibition of non-specific protein binding without strong interference of specific protein-binding reactions. Liposome structure and functionality was maintained following BGL014-modification, as the incorporation ratio of drug remained high. These results suggest that the BGL014 modification of liposomes is a promising approach to produce stable and long circulating drug carriers capable of selective binding to specific proteins.

  19. Rapid multi-wavelength optical assessment of circulating blood volume without a priori data

    NASA Astrophysics Data System (ADS)

    Loginova, Ekaterina V.; Zhidkova, Tatyana V.; Proskurnin, Mikhail A.; Zharov, Vladimir P.

    2016-03-01

    The measurement of circulating blood volume (CBV) is crucial in various medical conditions including surgery, iatrogenic problems, rapid fluid administration, transfusion of red blood cells, or trauma with extensive blood loss including battlefield injuries and other emergencies. Currently, available commercial techniques are invasive and time-consuming for trauma situations. Recently, we have proposed high-speed multi-wavelength photoacoustic/photothermal (PA/PT) flow cytometry for in vivo CBV assessment with multiple dyes as PA contrast agents (labels). As the first step, we have characterized the capability of this technique to monitor the clearance of three dyes (indocyanine green, methylene blue, and trypan blue) in an animal model. However, there are strong demands on improvements in PA/PT flow cytometry. As additional verification of our proof-of-concept of this technique, we performed optical photometric CBV measurements in vitro. Three label dyes—methylene blue, crystal violet and, partially, brilliant green—were selected for simultaneous photometric determination of the components of their two-dye mixtures in the circulating blood in vitro without any extra data (like hemoglobin absorption) known a priori. The tests of single dyes and their mixtures in a flow system simulating a blood transfusion system showed a negligible difference between the sensitivities of the determination of these dyes under batch and flow conditions. For individual dyes, the limits of detection of 3×10-6 M‒3×10-6 M in blood were achieved, which provided their continuous determination at a level of 10-5 M for the CBV assessment without a priori data on the matrix. The CBV assessment with errors no higher than 4% were obtained, and the possibility to apply the developed procedure for optical photometric (flow cytometry) with laser sources was shown.

  20. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure

    PubMed Central

    Fargali, Samira; Garcia, Angelo L.; Sadahiro, Masato; Jiang, Cheng; Janssen, William G.; Lin, Wei-Jye; Cogliani, Valeria; Elste, Alice; Mortillo, Steven; Cero, Cheryl; Veitenheimer, Britta; Graiani, Gallia; Pasinetti, Giulio M.; Mahata, Sushil K.; Osborn, John W.; Huntley, George W.; Phillips, Greg R.; Benson, Deanna L.; Bartolomucci, Alessandro; Salton, Stephen R.

    2014-01-01

    Secretion of proteins and neurotransmitters from large dense core vesicles (LDCVs) is a highly regulated process. Adrenal LDCV formation involves the granin proteins chromogranin A (CgA) and chromogranin B (CgB); CgA- and CgB-derived peptides regulate catecholamine levels and blood pressure. We investigated function of the granin VGF (nonacronymic) in LDCV formation and the regulation of catecholamine levels and blood pressure. Expression of exogenous VGF in nonendocrine NIH 3T3 fibroblasts resulted in the formation of LDCV-like structures and depolarization-induced VGF secretion. Analysis of germline VGF-knockout mouse adrenal medulla revealed decreased LDCV size in noradrenergic chromaffin cells, increased adrenal norepinephrine and epinephrine content and circulating plasma epinephrine, and decreased adrenal CgB. These neurochemical changes in VGF-knockout mice were associated with hypertension. Germline knock-in of human VGF1–615 into the mouse Vgf locus rescued the hypertensive knockout phenotype, while knock-in of a truncated human VGF1–524 that lacks several C-terminal peptides, including TLQP-21, resulted in a small but significant increase in systolic blood pressure compared to hVGF1–615 mice. Finally, acute and chronic administration of the VGF-derived peptide TLQP-21 to rodents decreased blood pressure. Our studies establish a role for VGF in adrenal LDCV formation and the regulation of catecholamine levels and blood pressure.—Fargali, S., Garcia, A. L., Sadahiro, M., Jiang, C., Janssen, W. G., Lin, W.-J., Cogliani, V., Elste, A., Mortillo, S., Cero, C., Veitenheimer, B., Graiani, G., Pasinetti, G. M., Mahata, S. K., Osborn, J. W., Huntley, G. W., Phillips, G. R., Benson, D. L., Bartolomucci, A., Salton, S. R. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. PMID:24497580

  1. Elasticity of nanoparticles influences their blood circulation, phagocytosis, endocytosis, and targeting.

    PubMed

    Anselmo, Aaron C; Zhang, Mengwen; Kumar, Sunny; Vogus, Douglas R; Menegatti, Stefano; Helgeson, Matthew E; Mitragotri, Samir

    2015-03-24

    The impact of physical and chemical modifications of nanoparticles on their biological function has been systemically investigated and exploited to improve their circulation and targeting. However, the impact of nanoparticles' flexibility (i.e., elastic modulus) on their function has been explored to a far lesser extent, and the potential benefits of tuning nanoparticle elasticity are not clear. Here, we describe a method to synthesize polyethylene glycol (PEG)-based hydrogel nanoparticles of uniform size (200 nm) with elastic moduli ranging from 0.255 to 3000 kPa. These particles are used to investigate the role of particle elasticity on key functions including blood circulation time, biodistribution, antibody-mediated targeting, endocytosis, and phagocytosis. Our results demonstrate that softer nanoparticles (10 kPa) offer enhanced circulation and subsequently enhanced targeting compared to harder nanoparticles (3000 kPa) in vivo. Furthermore, in vitro experiments show that softer nanoparticles exhibit significantly reduced cellular uptake in immune cells (J774 macrophages), endothelial cells (bEnd.3), and cancer cells (4T1). Tuning nanoparticle elasticity potentially offers a method to improve the biological fate of nanoparticles by offering enhanced circulation, reduced immune system uptake, and improved targeting.

  2. Blood circulation in muscles of the back in scoliosis deformity of the lumbar spine and under conditions of its correction.

    PubMed

    Kobyzev, E; Kononovich, N A; Krasnov, V V

    2014-10-01

    Experiments performed on dogs showed that the formation of scoliotic deformity of the lumbar spine sharply affects the hemodynamics of the back muscles, which manifested in asymmetric arterial blood fl ow, increased blood supply to the tissues, and impaired venous outflow. The changes were more pronounced on the apex of epy developing deformity. Correction of scoliotic deformity gradually restored blood circulation in muscles of the back. The use of methods of functional diagnostic for evaluation of the status of blood circulation in the tissues of the back has diagnostic value and allows evaluation of the treatment efficiency.

  3. [The unfolding of the blood circulation doctrine: the correspondence between William Harvey and Caspar Hofmann in May 1636].

    PubMed

    Rebollo, Regina André

    2002-01-01

    The present article analyzes the letters exchanged by Caspar Hofmann and William Harvey in 1636 and the delineation of the main questions and answers on the blood circulation theory. The first part of the article presents concepts about blood circulation according to the time's physiology; the second part presents the changes introduced by Harvey; the third and last part presents the debate between Hofmann and Harvey.

  4. Circulating blood monocytes traffic to and participate in the periprosthetic tissue inflammation

    PubMed Central

    Zhang, Kai; Jia, Tang-Hong; McQueen, David; Gong, Wei-Ming; Markel, David C.; Wooley, Paul H.

    2010-01-01

    Objective To examine the trafficking of human circulating blood monocytes and their influence on the inflammation of periprosthetic tissues using a novel mouse–human chimera model. Methods Periprosthetic tissue and bone chips from patients with aseptic prosthetic loosening were implanted into the muscles of immune-deficient SCID mice depleted of host macrophages by periodic intraperitoneal injection of anti-asialo GM1 rabbit sera (ASGM1). Autologous patient peripheral blood monocytes (PBMCs) were labeled with PKH2 fluorescent dye and injected intraperitoneally into the implanted animals. Mice were sacrificed 14 days after PBMC transfusion for molecular and histological analyses. Results Patient periprosthetic tissues were well tolerated in SCID mice and preserved a high level of viability. Cell trafficking studies revealed the accumulation of fluorescent PBMC within the xenografts, with total cell counts in the xenografts significantly increased following the systemic PBMC infusion. PBMC infusion also promoted the expression of IL-1, IL-6, TNFα, and RANK within the periprosthetic tissue. Conclusion Systemic PBMC migrated to the implanted periprosthetic tissues and contributed to the local inflammation. The data provide evidence that circulating blood monocytes may play a role in pathologic process during aseptic loosening of total joint replacement. PMID:19484187

  5. The clearance time of infused hematopoietic stem cell from the blood circulation.

    PubMed

    Donmez, Ayhan; Ozsan, Fatma; Arik, Bahar; Ozkayin, Nese; Cagirgan, Seckin; Mir, Sevgi; Vural, Filiz; Tombuloglu, Murat

    2013-04-01

    There is no detailed information about the clearance time of infused hematopoietic stem cell (HSC) from the blood circulation in humans. In this prospective study, peripheral blood CD34+ cell counts were detected during the 4days period following autologous HSC transplantation in 20 patients by means of flow cytometry. The median CD34+ cells were at the highest level in the first hour and decreased below pre-infusion values on the first day after HSC infusion. By nonparametric analysis, positive correlation was found between CD34+ cell levels at the first hour and the post-thaw CD34+ cell dose (r=0.57, p=0.01). An inverse correlation was determined between CD34+ cell levels at the first hour and neutrophil engraftment (r=-0.54, p=0.01). Compared with the patients having CD34+ cell count of ⩾2μL(-1) in the first hour following HSC infusion, the patients having CD34+ cell count of <2μL(-1) had delayed both neutrophil (20 vs. 12, p=0.008) and platelet (47 vs. 11, p=0.01) engraftments. Our results indicated that infused HSCs were removed from the blood circulation within 1day. In addition, CD34+ cell levels at the first hour may be used as an important indicator to predict the delay of neutrophil and platelet engraftments.

  6. Detection of an atypical teratoid rhabdoid brain tumor gene deletion in circulating blood using next-generation sequencing.

    PubMed

    Chakravadhanula, Madhavi; Tembe, Waibhav; Legendre, Christophe; Carpentieri, David; Liang, Winnie S; Bussey, Kimberly J; Carpten, John; Berens, Michael E; Bhardwaj, Ratan D

    2014-09-01

    Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy. Next, we used whole genome sequencing (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in patient's blood also. About 20% of the blood DNA sequencing reads matched the tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA aberrations are a promising biomarker for atypical teratoid rhabdoid tumor patients. The high percentage of tumor DNA detected in blood indicates that either circulating brain tumor cells lyse in the blood or that contents of brain tumor cells traverse a possibly compromised blood-brain barrier in this patient.

  7. [The control of the regulatory system of intracranial blood circulation in neurosurgical patients].

    PubMed

    Danilov, V I; Gorozhanin, A V; Nizamutdinov, S I

    1992-01-01

    The authors suggest the principles of evaluation of the condition of the system regulating the circulatory provision of cerebral physical and chemical homeostasis, as well as a measurement complex and a set of instrumentally recorded values for control over the cerebral arteries' and veins' response to unified loads of physical and chemical nature in patients with neurosurgical pathology. The scientific and practical significance of such an approach to evaluation of cerebral blood circulation is reasoned by the results of accumulated experience in controlling the activity of some regulations of circulatory provision of the brain in healthy females and males differing in age and in 114 patients with brain tumors.

  8. [Investigation into vegetative regulation of blood circulation during 7-day dry immersion].

    PubMed

    Eshmanova, A K; Luchinskaia, E S; Baevskiĭ, R M

    2008-01-01

    The paper presents the results of investigations into vegetative regulation of blood circulation and regulation modification by peroral amlodipine and myostimulation during 7-d dry immersion. It was shown that in immersion vegetative regulation readjusted towards predominance of the sympathetic mechanisms. Myostimulation and peroral amlodipine modified regulation substantially mobilizing high level suprasegmentary structures. It should be noted that amlodipine and myostimulation differ in mechanisms of their action on central regulation. Pharmaceutical intervention seems to have a more complex and varying effect on people including side-effects. Presumably, it was the cause of poor orthostatic tolerance of several test-subjects.

  9. Microfluidic, marker-free isolation of circulating tumor cells from blood samples.

    PubMed

    Karabacak, Nezihi Murat; Spuhler, Philipp S; Fachin, Fabio; Lim, Eugene J; Pai, Vincent; Ozkumur, Emre; Martel, Joseph M; Kojic, Nikola; Smith, Kyle; Chen, Pin-i; Yang, Jennifer; Hwang, Henry; Morgan, Bailey; Trautwein, Julie; Barber, Thomas A; Stott, Shannon L; Maheswaran, Shyamala; Kapur, Ravi; Haber, Daniel A; Toner, Mehmet

    2014-03-01

    The ability to isolate and analyze rare circulating tumor cells (CTCs) has the potential to further our understanding of cancer metastasis and enhance the care of cancer patients. In this protocol, we describe the procedure for isolating rare CTCs from blood samples by using tumor antigen-independent microfluidic CTC-iChip technology. The CTC-iChip uses deterministic lateral displacement, inertial focusing and magnetophoresis to sort up to 10⁷ cells/s. By using two-stage magnetophoresis and depletion antibodies against leukocytes, we achieve 3.8-log depletion of white blood cells and a 97% yield of rare cells with a sample processing rate of 8 ml of whole blood/h. The CTC-iChip is compatible with standard cytopathological and RNA-based characterization methods. This protocol describes device production, assembly, blood sample preparation, system setup and the CTC isolation process. Sorting 8 ml of blood sample requires 2 h including setup time, and chip production requires 2-5 d.

  10. Microfluidic, marker-free isolation of circulating tumor cells from blood samples

    PubMed Central

    Karabacak, Nezihi Murat; Spuhler, Philipp S; Fachin, Fabio; Lim, Eugene J; Pai, Vincent; Ozkumur, Emre; Martel, Joseph M; Kojic, Nikola; Smith, Kyle; Chen, Pin-i; Yang, Jennifer; Hwang, Henry; Morgan, Bailey; Trautwein, Julie; Barber, Thomas A; Stott, Shannon L; Maheswaran, Shyamala; Kapur, Ravi; Haber, Daniel A; Toner, Mehmet

    2014-01-01

    The ability to isolate and analyze rare circulating tumor cells (CTCs) has the potential to further our understanding of cancer metastasis and enhance the care of cancer patients. In this protocol, we describe the procedure for isolating rare CTCs from blood samples by using tumor antigen–independent microfluidic CTC-iChip technology. The CTC-iChip uses deterministic lateral displacement, inertial focusing and magnetophoresis to sort up to 107 cells/s. By using two-stage magnetophoresis and depletion antibodies against leukocytes, we achieve 3.8-log depletion of white blood cells and a 97% yield of rare cells with a sample processing rate of 8 ml of whole blood/h. The CTC-iChip is compatible with standard cytopathological and RNA-based characterization methods. This protocol describes device production, assembly, blood sample preparation, system setup and the CTC isolation process. Sorting 8 ml of blood sample requires 2 h including setup time, and chip production requires 2–5 d. PMID:24577360

  11. [Regulation of blood circulation in the surgical correction of portal hypertension].

    PubMed

    Shanin, Iu N; Kotiv, B N; Tsygan, V N; Iontsev, V I

    2011-03-01

    56 patients with portal hypertension were examined who underwent decompressive shunt surgery. Cardiorhytmography and integral rheography body were performed in different stages. In the late postoperative period, there were positive changes in the autonomic regulation of functions: reduced tension index and sympathetic influence on heart rhythm, increases the value of other indicators of heart rate variability. Due to an increase in heart rate and peripheral vascular resistance normalizes blood pressure while reducing the values of cardiac output. There is a further normalization of the reactivity of blood circulation: arterial pressure and vascular resistance during the functional test remained at a constant level of magnitude of shock and cardiac index significantly increased and then decreased to the level of the original values, which corresponds to the reaction apparently healthy. Disorders of regulation, state and reactivity of blood flow in portal hypertension, manifested: 1. Reduction of heart rate variability with a significant increase in sympathetic activity of autonomic nervous system. 2. Reduction of cardiac output and vascular resistance, heart rate, changes in physiological determination of hemodynamic parameters: Blood pressure is determined only by the vessel resistance. 3. Reduction of blood pressure in response to breath holding test.

  12. Aspirin Resistance and Promoting Blood Circulation and Removing Blood Stasis: Current Situation and Prospectives

    PubMed Central

    Wang, Jie; Xiong, Xingjiang; Feng, Bo

    2014-01-01

    Aspirin plays a crucial physiological and pathophysiological role in cardiovascular diseases and cerebrovascular diseases by irreversibly inhibiting thromboxane A2. However, some patients may be “resistant” to its effect. The resistance has close association with adverse cardiovascular outcomes and increased mortality, so that resolving the problem of aspirin resistance (AR) is widely concerned. By studying the correlation between AR and blood stasis syndrome (BSS), it is demonstrated that BSS may be one of the pathogenesis of AR in traditional Chinese medicine. Chinese herb and formulas definitely possess the advantage of whole body regulation by many ways and many targets. It is a new direction for treatment of AR to combine TCM and modern medicine to study the mechanism and prevention of AR. PMID:24696702

  13. Genetic profiling of tumours using both circulating free DNA and circulating tumour cells isolated from the same preserved whole blood sample.

    PubMed

    Rothwell, Dominic G; Smith, Nigel; Morris, Daniel; Leong, Hui Sun; Li, Yaoyong; Hollebecque, Antoine; Ayub, Mahmood; Carter, Louise; Antonello, Jenny; Franklin, Lynsey; Miller, Crispin; Blackhall, Fiona; Dive, Caroline; Brady, Ged

    2016-04-01

    Molecular information obtained from cancer patients' blood is an emerging and powerful research tool with immense potential as a companion diagnostic for patient stratification and monitoring. Blood, which can be sampled routinely, provides a means of inferring the current genetic status of patients' tumours via analysis of circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA). However, accurate assessment of both CTCs and ctDNA requires all blood cells to be maintained intact until samples are processed. This dictates for ctDNA analysis EDTA blood samples must be processed with 4 h of draw, severely limiting the use of ctDNA in multi-site trials. Here we describe a blood collection protocol that is amenable for analysis of both CTCs and ctDNA up to four days after blood collection. We demonstrate that yields of circulating free DNA (cfDNA) obtained from whole blood CellSave samples are equivalent to those obtained from conventional EDTA plasma processed within 4 h of blood draw. Targeted and genome-wide NGS revealed comparable DNA quality and resultant sequence information from cfDNA within CellSave and EDTA samples. We also demonstrate that CTCs and ctDNA can be isolated from the same patient blood sample, and give the same patterns of CNA enabling direct analysis of the genetic status of patients' tumours. In summary, our results demonstrate the utility of a simple approach that enabling robust molecular analysis of CTCs and cfDNA for genotype-directed therapies in multi-site clinical trials and represent a significant methodological improvement for clinical benefit. PMID:26639657

  14. Do GSM 900MHz signals affect cerebral blood circulation? A near-infrared spectrophotometry study

    NASA Astrophysics Data System (ADS)

    Wolf, Martin; Haensse, Daniel; Morren, Geert; Froehlich, Juerg

    2006-06-01

    Effects of GSM 900MHz signals (EMF) typical for a handheld mobile phone on the cerebral blood circulation were investigated using near-infrared spectrophotometry (NIRS) in a three armed (12W/kg, 1.2W/kg, sham), double blind, randomized crossover trial in 16 healthy volunteers. During exposure we observed borderline significant short term responses of oxyhemoglobin and deoxyhemoglobin concentration, which correspond to a decrease of cerebral blood flow and volume and were smaller than regular physiological changes. Due to the relatively high number of statistical tests, these responses may be spurious and require further studies. There was no detectable dose-response relation or long term response within 20min. The detection limit was a fraction of the regular physiological changes elicited by functional activation. Compared to previous studies using PET, NIRS provides a much higher time resolution, which allowed investigating the short term effects efficiently, noninvasively, without the use of radioactive tracers and with high sensitivity.

  15. Changes in blood-brain barrier function modify the neuroendocrine response to circulating substances.

    PubMed

    Jezová, D; Johansson, B B; Oprsalová, Z; Vigas, M

    1989-04-01

    It is known that various experimental, pathological and even physiological situations may be accompanied by transient increases in blood-brain barrier (BBB) permeability. The hypothesis that under such conditions the blood-borne substances can reach the active sites in the brain in concentrations high enough to influence central control of hormone release was verified in these studies. A suitable experimental model of BBB opening by protamine sulfate administration in conscious rats was introduced. Using this model it was shown that the dopaminergic blocker domperidone inhibited apomorphine-induced ACTH release if permeability of the BBB was increased, but not under normal conditions. It is suggested that the changes in BBB function can modify the neuroendocrine response also to other circulating substances and this may be an important, until now unconsidered phenomenon in neuroendocrine research. PMID:2541363

  16. [The prevalence of behavioral risk factors and diseases of blood circulation system].

    PubMed

    Maximova, T M; Belov, V B; Lushkina, N P

    2014-01-01

    The article is based on the data of "The study on global aging and adult health" (SAGE), a WHO international project carried out in 2007-2010. The sampling included respondents aged from 50 to 79 years old. The analysis covered such behavioral risk factors as tobacco smoking, physical activity, fruits consumption, etc. The results of measurement of blood pressure, body weight and body height were included into analysis. The prevalence of hypertension, angina pectoris and stroke was estimated The characteristics of prevalence of behavioral risk factors and types of their combination were established. The conclusion is made that in conditions of different status area and various degrees of physical exercises there is no possibility to make definite conclusion about real level of prevalence of diseases of blood circulation system in aged population.

  17. Higher blood flow and circulating NO products offset high-altitude hypoxia among Tibetans.

    PubMed

    Erzurum, S C; Ghosh, S; Janocha, A J; Xu, W; Bauer, S; Bryan, N S; Tejero, J; Hemann, C; Hille, R; Stuehr, D J; Feelisch, M; Beall, C M

    2007-11-01

    The low barometric pressure at high altitude causes lower arterial oxygen content among Tibetan highlanders, who maintain normal levels of oxygen use as indicated by basal and maximal oxygen consumption levels that are consistent with sea level predictions. This study tested the hypothesis that Tibetans resident at 4,200 m offset physiological hypoxia and achieve normal oxygen delivery by means of higher blood flow enabled by higher levels of bioactive forms of NO, the main endothelial factor regulating blood flow and vascular resistance. The natural experimental study design compared Tibetans at 4,200 m and U.S. residents at 206 m. Eighty-eight Tibetan and 50 U.S. resident volunteers (18-56 years of age, healthy, nonsmoking, nonhypertensive, not pregnant, with normal pulmonary function) participated. Forearm blood flow, an indicator of systemic blood flow, was measured noninvasively by using plethysmography at rest, after breathing supplemental oxygen, and after exercise. The Tibetans had more than double the forearm blood flow of low-altitude residents, resulting in greater than sea level oxygen delivery to tissues. In comparison to sea level controls, Tibetans had >10-fold-higher circulating concentrations of bioactive NO products, including plasma and red blood cell nitrate and nitroso proteins and plasma nitrite, but lower concentrations of iron nitrosyl complexes (HbFeIINO) in red blood cells. This suggests that NO production is increased and that metabolic pathways controlling formation of NO products are regulated differently among Tibetans. These findings shift attention from the traditional focus on pulmonary and hematological systems to vascular factors contributing to adaptation to high-altitude hypoxia. PMID:17971439

  18. Diagnostic Applications and Methods to Isolate Circulating Tumor Cells (CTCs) from Blood

    NASA Astrophysics Data System (ADS)

    Tang, Cha-Mei

    2013-03-01

    Each year a million new cancer cases are diagnosed in the United States. Ninety percent of the deaths will be the result of metastasis, not from the primary tumor. Tissue biopsy is a universally accepted tool for cancer diagnosis and determination of treatment. The procedure varies, but is invasive, costly, and can be fatal, and for these reasons is seldom repeated after initial diagnosis. Monitoring of treatment response and for possible relapse is usually done by CT or MRI scan, both of which are expensive and require the tumor to change size perceptibly. Further, cancer can mutate or develop resistance to therapeutics and require modification of the treatment regimen. The initial tissue biopsy often cannot reflect the disease as it progresses, requiring new biopsy samples to determine a change of treatment. All carcinomas, about 80% of all cancer, shed tumor cells into the circulation, most often at the later stages when treatment is more critical. These circulating tumor cells (CTCs) are the cause of metastasis, and can be isolated from patient blood to serve as ``liquid biopsy''. These CTCs contain a valuable trove of information that help both patient and clinician understand disease status. In addition to counting the number of CTCs (known to be a prognostic indicator of survival), CTCs can provide biomarker information such as protein expressions and gene mutations, amplifications, and translocations. This information can be used to determine treatment. During treatment, the number of intact and apoptotic CTCs can be measured on a repeated basis to measure the patient's response to treatment and disease progression. Following treatment, liquid biopsy can be repeated at regular intervals to watch for relapse. Methods to isolate CTCs can be grouped into three categories: i) immunocapture based on surface markers of CTCs, ii) size exclusion based on CTC size, typically larger than blood cells, and iii) negative selection utilizing red blood cell lysis, white

  19. [Evaluate activating blood circulation and dissipating blood stasis effect mechanism of foshousan on acute blood stasis rats on basis of metabolomic approach].

    PubMed

    Huang, Mei-Yan; Tang, Yu-Ping; Li, Wei-Xia; Shang, Er-Xin; Guo, Jian-Ming; Qian, Da-Wei; Duan, Jin-Ao

    2013-10-01

    Ice water bath and subcutaneous injection of adrenaline were used to establish the acute blood stasis model of rats. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to study the urine metabolic changes of acute blood stasis rats. Potential biomarkers were selected by variable importance projection, and identified on basis of MS information and databases. The metabolic pathways were predicted via MetPA database. To study the effect of Foshousan on endogenous metabolites of acute blood stasis model rats, find potential biomarkers, and explore the effect mechanism of Foshousan on activating blood circulation and dissipating blood stasis. Eleven potential biomarkers were identified with multivariate statistical analysis of urine metabolite profiles, and which also were used to explain the phenylalanine metabolism, tryptophan metabolism and sphingolipid metabolism. Those disturbed metabolic pathways in acute blood stasis rats could be regulated closely to normal state after Foshousan administration. Metabolomics has a bright prospect in the efficacy evaluation and effect mechanism elucidation of the traditional Chinese medicines.

  20. Chasing a ghost?--Issues with the determination of circulating levels of endotoxin in human blood.

    PubMed

    Gnauck, Anne; Lentle, Roger Graham; Kruger, Marlena Cathorina

    2016-01-01

    Reliable quantification of bacterial products such as endotoxin is important for the diagnosis of Gram-negative infection and for the monitoring of its treatment. Further, it is important to identify patients with persistent subclinical level of bacterial products in their systemic circulation as data from animal studies also suggest this may be correlated with the onset of metabolic syndrome. In this review, we first aim to describe the principles of the Limulus amoebocyte lysate (LAL) test, an assay that is used to quantify endotoxin, and the various shortcomings that must be addressed before it can become a reliable means of quantifying endotoxin in samples derived from blood. We then review published data regarding endotoxin levels in healthy subjects and those with sepsis, inflammatory bowel disease, liver disorders and metabolic disorders such as obesity and diabetes. We also review the evidence regarding influence of macronutrients in augmenting the levels of systemic endotoxin. The results of this review show that reported mean levels of endotoxin in the systemic circulation of healthy humans and of those with various clinical disorders vary over a wide range. Further, this review shows that a significant proportion of this variation can be related to the method that was used to prepare plasma and serum samples prior to assay and its ability to reduce the effect of various blood borne factors that interfere with the LAL assay. PMID:26732012

  1. PEG Branched Polymer for Functionalization of Nanomaterials with Ultralong Blood Circulation

    PubMed Central

    Prencipe, Giuseppe; Tabakman, Scott M.; Welsher, Kevin; Liu, Zhuang; Goodwin, Andrew P.; Zhang, Li; Henry, Joy; Dai, Hongjie

    2010-01-01

    Nanomaterials have been actively pursued for biological and medical applications in recent years. Here, we report the synthesis of several new poly(ethylene glycol) grafted branched polymers for functionalization of various nanomaterials including carbon nanotubes, gold nanoparticles (NPs), and gold nanorods (NRs), affording high aqueous solubility and stability for these materials. We synthesize different surfactant polymers based upon poly(γ-glutamic acid) (γPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the abundant free carboxylic acid groups of γPGA for attaching lipophilic species such as pyrene or phospholipid, which bind to nanomaterials via robust physisorption. Additionally, the remaining carboxylic acids on γPGA or the amine-reactive anhydrides of PMHC18 are then PEGylated, providing extended hydrophilic groups, affording polymeric amphiphiles. We show that single-walled carbon nanotubes (SWNTs), Au NPs, and NRs functionalized by the polymers exhibit high stability in aqueous solutions at different pH values, at elevated temperatures, and in serum. Morever, the polymer-coated SWNTs exhibit remarkably long blood circulation (t1/2 = 22.1 h) upon intravenous injection into mice, far exceeding the previous record of 5.4 h. The ultralong blood circulation time suggests greatly delayed clearance of nanomaterials by the reticuloendothelial system (RES) of mice, a highly desired property for in vivo applications of nanomaterials, including imaging and drug delivery. PMID:19173646

  2. Effects of repeated concentric and eccentric contractions on tendon blood circulation.

    PubMed

    Kubo, K

    2015-06-01

    Previous studies demonstrated that treatment involving eccentric training was effective in the conservative management of chronic tendinosis. However, the mechanisms for these phenomena are unknown. The purpose of this study was to compare changes in blood circulation of the tendons after the repeated concentric and eccentric contractions. 11 healthy males volunteered for this study. Subjects performed the repeated concentric (CON) and eccentric (ECC) contractions (5 sets of 10 maximal voluntary contractions) of the plantar flexors. During and after repeated contractions, oxyhemoglobin (Oxy), deoxyhemoglobin (Deoxy), total hemoglobin (THb), and oxygen saturation (StO2) of the Achilles tendons were measured using red laser lights. Oxy and THb increased during and after ECC, but not CON. Deoxy decreased during both CON and ECC. Increase in StO2 during and after ECC was greater than that during and after CON. These results suggested that changes in blood circulation of the Achilles tendon during and after repeated eccentric contractions were more remarkable than those during and after repeated concentric contractions.

  3. PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation.

    PubMed

    Prencipe, Giuseppe; Tabakman, Scott M; Welsher, Kevin; Liu, Zhuang; Goodwin, Andrew P; Zhang, Li; Henry, Joy; Dai, Hongjie

    2009-04-01

    Nanomaterials have been actively pursued for biological and medical applications in recent years. Here, we report the synthesis of several new poly(ethylene glycol) grafted branched polymers for functionalization of various nanomaterials including carbon nanotubes, gold nanoparticles (NPs), and gold nanorods (NRs), affording high aqueous solubility and stability for these materials. We synthesize different surfactant polymers based upon poly(gamma-glutamic acid) (gammaPGA) and poly(maleic anhydride-alt-1-octadecene) (PMHC18). We use the abundant free carboxylic acid groups of gammaPGA for attaching lipophilic species such as pyrene or phospholipid, which bind to nanomaterials via robust physisorption. Additionally, the remaining carboxylic acids on gammaPGA or the amine-reactive anhydrides of PMHC18 are then PEGylated, providing extended hydrophilic groups, affording polymeric amphiphiles. We show that single-walled carbon nanotubes (SWNTs), Au NPs, and NRs functionalized by the polymers exhibit high stability in aqueous solutions at different pH values, at elevated temperatures, and in serum. Moreover, the polymer-coated SWNTs exhibit remarkably long blood circulation (t(1/2) = 22.1 h) upon intravenous injection into mice, far exceeding the previous record of 5.4 h. The ultralong blood circulation time suggests greatly delayed clearance of nanomaterials by the reticuloendothelial system (RES) of mice, a highly desired property for in vivo applications of nanomaterials, including imaging and drug delivery.

  4. Retro-orbital blood acquisition facilitates circulating microRNA measurement in zebrafish with paracetamol hepatotoxicity.

    PubMed

    Vliegenthart, Adriaan D B; Starkey Lewis, Philip; Tucker, Carl S; Del Pozo, Jorge; Rider, Sebastein; Antoine, Daniel J; Dubost, Valérie; Westphal, Magdalena; Moulin, Pierre; Bailey, Matthew A; Moggs, Jonathan G; Goldring, Chris E; Park, B Kevin; Dear, James W

    2014-06-01

    Paracetamol is the commonest cause of acute liver failure in the Western world and biomarkers are needed that report early hepatotoxicity. The liver-enriched microRNA (miRNA), miR-122, is a promising biomarker currently being qualified in humans. For biomarker development and drug toxicity screening, the zebrafish has advantages over rodents; however, blood acquisition in this model remains technically challenging. We developed a method for collecting blood from the adult zebrafish by retro-orbital (RO) bleeding and compared it to the commonly used lateral incision method. The RO technique was more reliable in terms of the blood yield and minimum amount per fish. This new RO technique was used in a zebrafish model of paracetamol toxicity. Paracetamol induced dose-dependent increases in liver cell necrosis, serum alanine transaminase activity, and mortality. In situ hybridization localized expression of miR-122 to the cytoplasm of zebrafish hepatocytes. After collection by RO bleeding, serum miR-122 could be measured and this miRNA was substantially increased by paracetamol 24 h after exposure, an increase that was prevented by delayed (3 h poststart of paracetamol exposure) treatment with acetylcysteine. In summary, collection of blood by RO bleeding facilitated measurement of miR-122 in a zebrafish model of paracetamol hepatotoxicity. The zebrafish represents a new species for measurement of circulating miRNA biomarkers that are translational and can bridge between fish and humans.

  5. DECREASED LEVEL OF CORD BLOOD CIRCULATING ENDOTHELIAL COLONY-FORMING CELLS IN PREECLAMPSIA

    PubMed Central

    Muñoz-Hernandez, Rocio; Miranda, Maria L.; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M.; Dominguez-Simeon, Maria J.; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M.

    2014-01-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation and migration towards VEGF-A and FGF-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P = .04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

  6. Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia.

    PubMed

    Muñoz-Hernandez, Rocio; Miranda, Maria L; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M; Dominguez-Simeon, Maria J; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M

    2014-07-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation, and migration toward vascular endothelial growth factor-A and fibroblast growth factor-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P=0.04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events.

  7. Systematic assessment of blood circulation time of functionalized upconversion nanoparticles in the chick embryo

    NASA Astrophysics Data System (ADS)

    Nadort, Annemarie; Liang, Liuen; Grebenik, Ekaterina; Guller, Anna; Lu, Yiqing; Qian, Yi; Goldys, Ewa; Zvyagin, Andrei

    2015-12-01

    Nanoparticle-based delivery of drugs and contrast agents holds great promise in cancer research, because of the increased delivery efficiency compared to `free' drugs and dyes. A versatile platform to investigate nanotechnology is the chick embryo chorioallantoic membrane tumour model, due to its availability (easy, cheap) and accessibility (interventions, imaging). In our group, we developed this model using several tumour cell lines (e.g. breast cancer, colon cancer). In addition, we have synthesized in-house silica coated photoluminescent upconversion nanoparticles with several functional groups (COOH, NH2, PEG). In this work we will present the systematic assessment of their in vivo blood circulation times. To this end, we injected chick embryos grown ex ovo with the functionalized UCNPs and obtained a small amount of blood at several time points after injection to create blood smears The UCNP signal from the blood smears was quantified using a modified inverted microscope imaging set-up. The results of this systematic study are valuable to optimize biochemistry protocols and guide nanomedicine advancement in the versatile chick embryo tumour model.

  8. In vivo circulation, clearance, and biodistribution of polyglycerol grafted functional red blood cells.

    PubMed

    Chapanian, Rafi; Constantinescu, Iren; Brooks, Donald E; Scott, Mark D; Kizhakkedathu, Jayachandran N

    2012-04-01

    The in vivo circulation of hyperbranched polyglycerol (HPG) grafted red blood cells (RBCs) was investigated in mice. The number of HPG molecules grafted per RBC was measured using tritium labeled HPGs ((3)H-HPG) of different molecular weights; the values ranged from 1 × 10(5) to 2 × 10(6) molecules per RBC. HPG-grafted RBCs were characterized in vitro by measuring the electrophoretic mobility, complement mediated lysis, and osmotic fragility. Our results show that RBCs grafted with 1.5 × 10(5) HPG molecules per RBC having molecular weights 20 and 60 kDa have similar characteristics as that of control RBCs. The in vivo circulation of HPG-grafted RBCs was measured by a tail vain injection of (3)H-HPG60K-RBC in mice. The radioactivity of isolated RBCs, whole blood, plasma, different organs, urine and feces was evaluated at different time intervals. The portion of (3)H-HPG60K-RBC that survived the first day in mice (52%) remained in circulation for 50 days. Minimal accumulation radioactivity in organs other than liver and spleen was observed suggesting the normal clearance mechanism of modified RBCs. Animals gained normal weights and no abnormalities observed in necropsy analysis. The stability of the ester-amide linker between the RBC and HPG was evaluated by comparing the clearance rate of (3)H-HPG60K-RBC and PKH-26 lipid fluorescent membrane marker labeled HPG60K-RBCs. HPG modified RBCs combine the many advantages of a dendritic polymer and RBCs, and hold great promise in systemic drug delivery and other applications of functional RBC.

  9. Promoting blood circulation for removing blood stasis therapy for acute intracerebral hemorrhage: a systematic review and meta-analysis

    PubMed Central

    Li, Hui-qin; Wei, Jing-jing; Xia, Wan; Li, Ji-huang; Liu, Ai-ju; Yin, Su-bing; Wang, Chen; Song, Liang; Wang, Yan; Zheng, Guo-qing; Fan, Ji-ping

    2015-01-01

    Aim: To conduct a systematic review and meta-analysis to assess the current evidence available regarding the promoting blood circulation and removing blood stasis (PBCRBS) therapy for Chinese patients with acute intracerebral hemorrhage (ICH). Methods: Six databases were searched from their inception to November 2013. The studies assessed in ≥4 domains with 'yes' were selected for detailed assessment and meta-analysis. The herbal compositions for PBCRBS therapy for acute ICH patients were also assessed. Results: From the 6 databases, 292 studies claimed randomized-controlled clinical trials (RCTs). Nine studies with 798 individuals were assessed in ≥4 domains with 'yes' by using the Cochrane RoB tool. Meta-analysis showed that PBCRBS monotherapy and adjuvant therapy for acute ICH could improve the neurological function deficit, reduce the volume of hematoma and perihematomal edema, and lower the mortality rate and dependency. Moreover, there were fewer adverse effects when compared with Western conventional medication controls. Xueshuantong Injection and Fufang Danshen Injection, Buyang Huanwu Decoction and Liangxue Tongyu formula, and three herbs (danshen root, sanqi and leech) were the most commonly used Chinese herbal patent injections, herbal prescriptions and single herbs, respectively. Conclusion: Despite the apparently positive findings, it is premature to conclude that there is sufficient efficacy and safety of PBCRBS for ICH because of the high clinical heterogeneity of the included studies and small number of trials in the meta-analysis. Further large sample-sizes and rigorously designed RCTs are needed. PMID:25960132

  10. Maternal Body-Mass Index and Cord Blood Circulating Endothelial Colony-Forming Cells

    PubMed Central

    Lin, Ruei-Zeng; Miranda, Maria L.; Vallejo-Vaz, Antonio J.; Stiefel, Pablo; Praena-Fernández, Juan M.; Bernal-Bermejo, Jose; Jimenez-Jimenez, Luis M.; Villar, Jose; Melero-Martin, Juan M.

    2013-01-01

    Objective Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that are particularly abundant in umbilical cord blood. We sought to determine whether ECFC abundance in cord blood is associated with maternal body-mass index (BMI) in non-pathological pregnancies. Study design We measured the level of ECFCs in the cord blood of neonates (n=27) born from non-obese healthy mothers with non-pathological pregnancies and examined whether ECFC abundance correlated with maternal BMI. We also examined the effect of maternal BMI on ECFC phenotype and function using angiogenic and vasculogenic assays. Results We observed variation in ECFC abundance among subjects and found a positive correlation between pre-pregnancy maternal BMI and ECFC content (r=0.51, P=0.007), which was independent of other obstetric factors. Despite this variation, ECFC phenotype and functionality were deemed normal and highly similar between subjects with maternal BMI <25 kg/m2 and BMI between 25–30 kg/m2, including the ability to form vascular networks in vivo. Conclusions This study underlines the need to consider maternal BMI as a potential confounding factor for cord blood levels of ECFCs in future comparative studies between healthy and pathological pregnancies. Endothelial colony-forming cells (ECFCs) are a subset of progenitor cells that circulate in peripheral blood and can give rise to endothelial cells (1,2), contributing to the formation of new vasculature and the maintenance of vascular integrity (3–5). The mechanisms that regulate the abundance of these cells in vivo remain poorly understood. ECFCs are rare in adult peripheral blood (1,2,10). In contrast, there is an elevated number of these cells in fetal blood during the third trimester of pregnancy (11–13). Emerging evidence indicates that deleterious conditions during fetal life can impair ECFC content and function. For instance, offspring of diabetic mothers have been shown to have

  11. Flow of a circulating tumor cell and red blood cells in microvessels

    NASA Astrophysics Data System (ADS)

    Takeishi, Naoki; Imai, Yohsuke; Yamaguchi, Takami; Ishikawa, Takuji

    2015-12-01

    Quantifying the behavior of circulating tumor cells (CTCs) in the blood stream is of fundamental importance for understanding metastasis. Here, we investigate the flow mode and velocity of CTCs interacting with red blood cells (RBCs) in various sized microvessels. The flow of leukocytes in microvessels has been described previously; a leukocyte forms a train with RBCs in small microvessels and exhibits margination in large microvessels. Important differences in the physical properties of leukocytes and CTCs result from size. The dimensions of leukocytes are similar to those of RBCs, but CTCs are significantly larger. We investigate numerically the size effects on the flow mode and the cell velocity, and we identify similarities and differences between leukocytes and CTCs. We find that a transition from train formation to margination occurs when (R -a ) /tR≈1 , where R is the vessel radius, a is the cell radius, and tR is the thickness of RBCs, but that the motion of RBCs differs from the case of leukocytes. Our results also show that the velocities of CTCs and leukocytes are larger than the average blood velocity, but only CTCs move faster than RBCs for microvessels of R /a ≈1.5 -2.0 . These findings are expected to be useful not only for understanding metastasis, but also for developing microfluidic devices.

  12. Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

    SciTech Connect

    Beck, T.; Krieglstein, J.

    1987-03-01

    The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O/sub 2/. Hypoxia affected a marked hypotension, hypocapnia and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40-70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU and were detectable in cortical gray matter. Color-coded (/sup 14/C)2-deoxy-D-glucose autoradiograms of rat brain are shown. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggests a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur.

  13. Interrelationship between excessive levels of circulating androgens in blood and ovulatory failure.

    PubMed

    Parker, C R; Mahesh, V B

    1976-08-01

    The association of excessive circulating androgens in blood and ovulatory failure in women is well documented in a variety of clinical conditions. The restoration of ovulatory function by wedge resection of the polycystic ovary, by the administration of glucocorticoids or removal of tumors of the adrenal or ovary--measures that also reduce the level of circulating androgens--is also well documented. In view of the many hypotheses of adrenal and ovarian abnormalities and disorders of the hypothalamic-pituitary axis in the human, resulting in hirsutism and ovulatory failure, a normal intact rat model was developed to study the effect of androgens on ovulation. The administration of a weak androgen, dehydroepiandrosterone (DHA), to immature rats resulted in a single precocious ovulation followed by ovulatory failure. The conversion of DHA to estrogens appeared to be the principle mechanism for the precocious ovulation. The steps appeared to be an elevation in blood estradiol, followed by the depletion of cytoplasmic estradiol receptors of the hypothalamus and pituitary and the gonadotropin surge leading to ovulation. These events appeared to be similar to those occuring in the adult cycling rat, in precocious puberty induced by the administration of pregnant mare serum gonadotropins and during the onset of natural puberty. The role of estrogens in inducing the precocious ovulation was further supported by the absence of precocious ovulation in animals in which the conversion of DHA to estrogens was blocked or by administering androgens that could not be converted to estrogens. In contrast, the subsequent ovulatory failure could not be explained entirely by the conversion of DHA to estrogens. There was a considerable time lag between the withdrawal of DHA treatment and the replenishment of pituitary and hypothalamic cytoplasmic estradiol receptors. Unlike those of the cycling animal, the receptors were not replenished when the levels of circulating estradiol in blood

  14. Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation.

    PubMed

    Qureshi, M Umar; Vaughan, Gareth D A; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S; Olufsen, Mette S; Hill, N A

    2014-10-01

    A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281-1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of 'large' arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the 'smaller' arteries and veins of radii ≥ 50 μm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung. PMID:24610385

  15. Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation.

    PubMed

    Qureshi, M Umar; Vaughan, Gareth D A; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S; Olufsen, Mette S; Hill, N A

    2014-10-01

    A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281-1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of 'large' arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the 'smaller' arteries and veins of radii ≥ 50 μm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung.

  16. [The multiple organ failure syndrome after cardiac surgery with artificial blood circulation].

    PubMed

    Babaev, M A; Eremenko, A A; Minbolatova, N M; Dzemeshkevich, S L

    2013-01-01

    The 10-year study of etiology, pathogenesis, diagnostic, treatment and prevention of the multiple organ failure syndrome (MOFS) after cardiovascular operations with artificial blood circulation was conducted in the SCS. 4383 patients, aged 16-75 years, were observed. Of them, MOFS was diagnosed in 206 (4.7%) patients. Extracorporal detoxication was used in 385 patients. When used in patients with complicated postoperative period, the extracorporal detoxication prevents MOFS and decreases lethality in 3 times (from 59.3 to 19.2%). The method is indicated to patients with MOFS severity estimated of 13.5 points and damage of 5-6 organ systems. Herewith the duration of veno-venous ultrahemodiafiltration should not exceed 80 hours and the number of sessions should not be more then 3.

  17. [The seasonality of population contacts with medical organizations because of diseases of blood circulation system].

    PubMed

    Maksimova, T M; Belov, V B; Saurina, O S; Lushkina, N P

    2014-01-01

    The comprehension of significance of health impacting of such unchangeable factors as climate and atmospheric phenomenons allows carrying out measures to decrease their negative effect on human health. The data of study implemented in Orel in 2009-2012 made it possible to distribute the annual totality of diagnoses registered in medical organizations on the groups of diseases of blood circulation system according ICD-10. The analysis established lower level of visits to physician because of these conditions both in ambulatory polyclinic institutions and hospital during summer period. The corresponding percentage came to 21.9% out of all diagnoses in polyclinic and 22% in hospital at highest levels of 27% in summer period. Therefore, in development of population contacts with medical organizations an expressed seasonality is detected. This occurrence is possibly related to characteristics of development of pathological conditions in different seasons.

  18. [Magnetic field numerical calculation and analysis for magnetic coupling of centrifugal blood pump for extracorporeal circulation].

    PubMed

    Hu, Zhaoyan; Lu, Lijun; Zhang, Tianyi; Chen, Zhenglong; Zhang, Tao

    2013-12-01

    This paper mainly studies the driving system of centrifugal blood pump for extracorporeal circulation, with the core being disc magnetic coupling. Structure parameters of disc magnetic coupling are related to the ability of transferring magnetic torque. Therefore, it is necessary to carry out disc magnetic coupling permanent magnet pole number (n), air gap length (L(g)), permanent magnet thickness (L(m)), permanent magnet body inside diameter (R(i)) and outside diameter (R(o)), etc. thoroughly. This paper adopts the three-dimensional static magnetic field edge element method of Ansys for numerical calculation, and analyses the relations of magnetic coupling each parameter to transmission magnetic torque. It provides a good theory basis and calculation method for further optimization of the disc magnetic coupling.

  19. Angiographic circulation time and cerebral blood flow during balloon test occlusion of the internal carotid artery

    PubMed Central

    Sato, Kenichi; Shimizu, Hiroaki; Inoue, Takashi; Fujimura, Miki; Matsumoto, Yasushi; Kondo, Ryushi; Endo, Hidenori; Sonoda, Yukihiko; Tominaga, Teiji

    2014-01-01

    Angiography-based balloon test occlusion (BTO) has been empirically used to predict tolerance to permanent carotid artery occlusion. We tested the hypothesis that the laterality of the hemispheric circulation time (HCT) of the contrast medium at cerebral angiography would reflect bilateral asymmetry of the cerebral blood flow (CBF) during BTO. Thirty-one consecutive patients who underwent BTO of the internal carotid artery were retrospectively analyzed. HCT was defined as the interval between the time-to-peak in the middle cerebral artery and the cortical veins calculated using time-density curve. The difference in HCT between the occluded and nonoccluded side was calculated at the carotid or dominant vertebral angiograms obtained during BTO. We estimated the correlation between the difference in HCT and bilateral asymmetry of the CBF, which was quantitatively determined by single-photon emission computed tomography. The HCT was 5.3±1.5 seconds and regional CBF was 41.3±11.3 mL/100 g per minute in the occluded side, compared with 3.6±0.9 seconds and 48.4±14.9 mL/100 g per minute in the nonoccluded side, respectively. The difference in HCT was strongly correlated with the asymmetry ratio of the CBF (r2=0.89, P<0.0001). Angiographically based measurement of the cerebral circulation time can provide valuable information concerning cerebral hemodynamics. PMID:24103905

  20. [The autonomous nervous system and blood circulation system--homeostasis and homeokinesis during spine surgery].

    PubMed

    Mikaelian, K P; Zaĭtsev, A Iu; Svetlov, V A; Gur'ianov, V A; Dubrovin, K V

    2012-01-01

    In 30-surgical patients, operated for degenerative-dystrophic changes of the spine (microdiscectomy), with due regard for initial condition of the ANS (differentiated by Kerdo index), homeokinesis state has been studied. The circulatory system function was controlled with the use of a standard monitoring and central hemodynamics indices, that has allowed to mark out Hyper-and Hypo - eukinetic circulation types. Microdiscectomy performed under combined anesthesia (N2O/ O2 - 0.5) with fentanyl and sevorane. It was found that 68% of the surveyed patients directly before the surgery had a lack of homeokinesis (vagotonia). Comparison of the reaction of the autonomous nervous system and the circulatory system to premedication revealed that the change in the number of vagotonic patients and patients with hypokinetic type of hemodynamics had a direct linear dependence, and the number of sympathotonic patients and patients with hypokinetic type of hemodynamics -- the reverse one. Surgery, intraoperative pharmacological load, change of the body in sympathotonic patients accompanied with changes in Central hemodynamics (low afterload, eukinetic HI values), characteristic for physiological homeokinesis, which was not observed in vagotonic patients, which have remained unsuccessful (dysadaptative) hypokinetic type of blood circulation.

  1. Characterization of the Occult Hepatitis B Virus Variants Circulating among the Blood Donors from Eastern India

    PubMed Central

    Biswas, Avik; Chandra, Partha Kumar; Banerjee, Arup; Chakraborty, Subhashish; Bhattacharya, Prasun; Chakrabarti, Sekhar; Chakravarty, Runu

    2013-01-01

    A previous study from West Bengal documented very high rate of occult HBV infection (OBI) among the HBsAg negative blood donors. This study was aimed to characterize the OBI strains circulating among the blood donors and to estimate the risk associated with the prevailing viral variants/mutants. Blood samples from 2195 voluntary blood donors were included in the study. HBsAg, HBeAg, anti-HBc, and anti-HBs statuses of the samples were done by ELISA based detection. PCR amplification and sequencing were done to determine HBV genotypes, basal core promoter (BCP), and precore (Pre-C) mutations. Among the study samples, 268 were anti-HBc positive/HBsAg negative, among which 65 (24.25%) were HBV DNA positive. Phylogenetic analysis revealed the presence of HBV/D (87.23%), HBV/A (8.51%), and HBV/C (4.26%) (P < 0.0001). HBV/D3 (65.85%) was the significantly prevalent subgenotype over HBV/D2 (26.83%) and HBV/D1 (7.31%) (P = 0.0003). Considerable prevalence of differential BCP (1752C, 1753C, 1762T/1764A, 1753C+1762T/1764A, 1773C, and 1814C) and reverse transcriptase (rt) gene (rtI91L, rtL93P, rtS106C, rtR110G, rtN118T, rtS119T, rtY126H, rtG127W/R, rtC136R, and rtY158H) mutations was identified. Association of specific HBV subgenotypes with OBI was interesting and needs further study. Clinically relevant mutations were prevalent among the OBI strains which are of serious concern. PMID:24302857

  2. Engineered stealth porous silicon nanoparticles via surface encapsulation of bovine serum albumin for prolonging blood circulation in vivo.

    PubMed

    Xia, Bing; Zhang, Wenyi; Shi, Jisen; Xiao, Shou-jun

    2013-11-27

    Luminescent porous silicon nanoparticles (PSiNPs) have been widely used as drug delivery. However, fast biodegradation and short blood circulation have been major challenges for their biomedical applications. Herein, bovine serum albumin was readily encapsulated onto alkyl-terminated PSiNPs surfaces via hydrophobic interaction, which could significantly improve their water-dispersibility and long-term stability under physiological conditions. Furthermore, compared with PSiNPs alone, PSiNPs coated with bovine serum albumin remarkably reduced nonspecific cellular uptake in vitro and prolonged blood circulation in vivo.

  3. Steroid-like compounds in Chinese medicines promote blood circulation via inhibition of Na+/K+-ATPase

    PubMed Central

    Chen, Ronald JY; Chung, Tse-yu; Li, Feng-yin; Yang, Wei-hung; Jinn, Tzyy-rong; Tzen, Jason TC

    2010-01-01

    Aim: To examine if steroid-like compounds found in many Chinese medicinal products conventionally used for the promotion of blood circulation may act as active components via the same molecular mechanism triggered by cardiac glycosides, such as ouabain. Methods: The inhibitory potency of ouabain and the identified steroid-like compounds on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of these compounds to Na+/K+-ATPase. Results: All the examined steroid-like compounds displayed more or less inhibition on Na+/K+-ATPase, with bufalin (structurally almost equivalent to ouabain) exhibiting significantly higher inhibitory potency than the others. In the pentacyclic triterpenoids examined, ursolic acid and oleanolic acid were moderate inhibitors of Na+/K+-ATPase, and their inhibitory potency was comparable to that of ginsenoside Rh2. The relatively high inhibitory potency of ursolic acid or oleanolic acid was due to the formation of a hydrogen bond between its carboxyl group and the Ile322 residue in the deep cavity close to two K+ binding sites of Na+/K+-ATPase. Moreover, the drastic difference observed in the inhibitory potency of ouabain, bufalin, ginsenoside Rh2, and pentacyclic triterpenoids is ascribed mainly to the number of hydrogen bonds and partially to the strength of hydrophobic interaction between the compounds and residues around the deep cavity of Na+/K+-ATPase. Conclusion: Steroid-like compounds seem to contribute to therapeutic effects of many cardioactive Chinese medicinal products. Chinese herbs, such as Prunella vulgaris L, rich in ursolic acid, oleanolic acid and their glycoside derivatives may be adequate sources for cardiac therapy via effective inhibition on Na+/K+-ATPase. PMID:20523340

  4. Effects of spinal cord stimulation on peripheral blood circulation in rats with streptozotocin-induced diabetes.

    PubMed

    Wu, Mingyuan; Thorkilsen, Marielouise Muus; Qin, Chao; Farber, Jay P; Linderoth, Bengt; Foreman, Robert D

    2007-07-01

    Objective.  The aim of this study was to investigate the effects of spinal cord stimulation (SCS) on peripheral circulation in rats with streptozotocin (STZ)-induced diabetes. Materials and Methods.  Four weeks after streptozotocin or vehicle was injected (i.p.) in male Sprague-Dawley rats, SCS-induced vasodilation was examined. Results.  Plasma glucose concentration was significantly higher in diabetic rats than in the control animals. Motor threshold (MT) was significantly higher in diabetic rats than in control rats. SCS-induced vasodilation was attenuated at 90% of the MT, but not at 30% and 60% of MT in diabetic rats when compared to control rats (p < 0.001, N = 13). Furthermore, increasing SCS from 30% to 90% of MT typically produced a progressive increase in blood flow in control rats but not in diabetic rats (p < 0.01, N = 13). Conclusion.  This study suggested that SCS-induced vasodilation improves peripheral blood flow, although the pathways were partially impaired in the diabetic condition.

  5. Gene expression profiling of circulating tumor cells and peripheral blood mononuclear cells from breast cancer patients

    PubMed Central

    Hensler, Michal; Vančurová, Irena; Becht, Etienne; Palata, Ondřej; Strnad, Pavel; Tesařová, Petra; Čabiňaková, Michaela; Švec, David; Kubista, Mikael; Bartůňková, Jiřina; Špíšek, Radek; Sojka, Luděk

    2016-01-01

    ABSTRACT Circulating tumor cells (CTCs) are cancer cells that are released from a tumor into the bloodstream. The presence of CTCs in peripheral blood has been associated with metastasis formation in patients with breast cancer. Therefore, the molecular characterization of CTCs may improve diagnostics and support treatment decisions. We performed gene expression profiling to evaluate the enriched CTCs and peripheral blood mononuclear cells (PBMCs) of breast cancer patients using an expression panel of 55 breast cancer-associated genes. The study revealed several significantly differentially expressed genes in the CTC-positive samples, including a few that were exclusively expressed in these cells. However, the expression of these genes was barely detectable in the PBMC samples. Some genes were differentially expressed in PBMCs, and the expression of these genes was correlated with tumor grade and the formation of metastasis. In this study, we have shown that the enriched CTCs of breast cancer patients overexpress genes involved in proteolytic degradation of the extracellular matrix (ECM) as well as genes that play important roles in the epithelial-mesenchymal transition (EMT) process that may occur in these cells. PMID:27141386

  6. From the discovery of the circulation of the blood to the first steps in hemorheology: part 1.

    PubMed

    Martins e Silva, J

    2009-11-01

    In this article (the first of two on the subject) a brief historical review is presented of the prevailing ideas on the nature of the blood and its circulation from antiquity to the 16th century, when the problem was solved by William Harvey. On the basis of vivisection of various types of animals, Harvey constructed a general and logical model for the whole systemic circulation, which contradicted previous concepts, mainly those that had been put forward by Galen fourteen centuries before. The influence that Galen still exercised on virtually all areas of medicine justified Harvey's hesitations and scruples, forcing him to delay publishing his conclusions for thirteen years. It also explains the controversy with fellow physicians on the subject, which continued until his death. However, through careful observation and painstaking investigation, Harvey demonstrated clearly that the heart was the central organ of the circulatory system, on which depended the propulsion of the blood to the arteries and its subsequent return by different vessels, the veins, to its starting point. The blood coming from the heart was different from that which returned to the organ, the difference (in color and fluidity) being attributed to the presence of constituents which nourished the organism it irrigated. Harvey characterized blood pulsation as the result of the arteries filling with arterial blood during each heart contraction. He demonstrated that the arterial blood left the heart by contraction of the left ventricle, which happened simultaneously with contraction of the right ventricle and, in both, after the contraction of the atria. He confirmed that blood passed through the lung circulation from the right ventricle to the left atrium and from there to the left ventricle. By calculating the volume of blood pumped daily by the heart, Harvey reasoned that the blood could not be consumed by the body and would have to circulate continually through the heart and vascular network

  7. Effects of Solar Particle Event-Like Proton Radiation and/or Simulated Microgravity on Circulating Mouse Blood Cells

    PubMed Central

    Romero-Weaver, Ana L.; Lin, Liyong; Carabe-Fernandez, Alejandro; Kennedy, Ann R.

    2014-01-01

    Astronauts traveling in space missions outside of low Earth orbit will be exposed for longer times to a microgravity environment. In addition, the increased travel time involved in exploration class missions will result in an increased risk of exposure to significant doses of solar particle event (SPE) radiation. Both conditions could significantly affect the number of circulating blood cells. Therefore, it is critical to determine the combined effects of exposure to both microgravity and SPE radiation. The purpose of the present study was to assess these risks by evaluating the effects of SPE-like proton radiation and/or microgravity, as simulated with the hindlimb unloading (HU) system, on circulating blood cells using mouse as a model system. The results indicate that exposure to HU alone caused minimal or no significant changes in mouse circulating blood cell numbers. The exposure of mice to SPE-like proton radiation with or without HU treatment caused a significant decrease in the number of circulating lymphocytes, granulocytes and platelets. The reduced numbers of circulating lymphocytes, granulocytes, and platelets, resulting from the SPE-like proton radiation exposure, with or without HU treatment, in mice suggest that astronauts participating in exploration class missions may be at greater risk of developing infections and thrombotic diseases; thus, countermeasures may be necessary for these biological endpoints. PMID:25360441

  8. Effects of Solar Particle Event-Like Proton Radiation and/or Simulated Microgravity on Circulating Mouse Blood Cells.

    PubMed

    Romero-Weaver, Ana L; Lin, Liyong; Carabe-Fernandez, Alejandro; Kennedy, Ann R

    2014-08-01

    Astronauts traveling in space missions outside of low Earth orbit will be exposed for longer times to a microgravity environment. In addition, the increased travel time involved in exploration class missions will result in an increased risk of exposure to significant doses of solar particle event (SPE) radiation. Both conditions could significantly affect the number of circulating blood cells. Therefore, it is critical to determine the combined effects of exposure to both microgravity and SPE radiation. The purpose of the present study was to assess these risks by evaluating the effects of SPE-like proton radiation and/or microgravity, as simulated with the hindlimb unloading (HU) system, on circulating blood cells using mouse as a model system. The results indicate that exposure to HU alone caused minimal or no significant changes in mouse circulating blood cell numbers. The exposure of mice to SPE-like proton radiation with or without HU treatment caused a significant decrease in the number of circulating lymphocytes, granulocytes and platelets. The reduced numbers of circulating lymphocytes, granulocytes, and platelets, resulting from the SPE-like proton radiation exposure, with or without HU treatment, in mice suggest that astronauts participating in exploration class missions may be at greater risk of developing infections and thrombotic diseases; thus, countermeasures may be necessary for these biological endpoints.

  9. Effects of Solar Particle Event-Like Proton Radiation and/or Simulated Microgravity on Circulating Mouse Blood Cells.

    PubMed

    Romero-Weaver, Ana L; Lin, Liyong; Carabe-Fernandez, Alejandro; Kennedy, Ann R

    2014-08-01

    Astronauts traveling in space missions outside of low Earth orbit will be exposed for longer times to a microgravity environment. In addition, the increased travel time involved in exploration class missions will result in an increased risk of exposure to significant doses of solar particle event (SPE) radiation. Both conditions could significantly affect the number of circulating blood cells. Therefore, it is critical to determine the combined effects of exposure to both microgravity and SPE radiation. The purpose of the present study was to assess these risks by evaluating the effects of SPE-like proton radiation and/or microgravity, as simulated with the hindlimb unloading (HU) system, on circulating blood cells using mouse as a model system. The results indicate that exposure to HU alone caused minimal or no significant changes in mouse circulating blood cell numbers. The exposure of mice to SPE-like proton radiation with or without HU treatment caused a significant decrease in the number of circulating lymphocytes, granulocytes and platelets. The reduced numbers of circulating lymphocytes, granulocytes, and platelets, resulting from the SPE-like proton radiation exposure, with or without HU treatment, in mice suggest that astronauts participating in exploration class missions may be at greater risk of developing infections and thrombotic diseases; thus, countermeasures may be necessary for these biological endpoints. PMID:25360441

  10. Instruction of Circulating Endothelial Progenitors In Vitro towards Specialized Blood-Brain Barrier and Arterial Phenotypes

    PubMed Central

    Ponio, Julie Boyer-Di; El-Ayoubi, Fida; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Driancourt, Catherine; Godet, Maeva; Perrière, Nicolas; Guillevic, Oriane; Couraud, Pierre Olivier; Uzan, Georges

    2014-01-01

    Objective The vascular system is adapted to specific functions in different tissues and organs. Vascular endothelial cells are important elements of this adaptation, leading to the concept of ‘specialized endothelial cells’. The phenotype of these cells is highly dependent on their specific microenvironment and when isolated and cultured, they lose their specific features after few passages, making models using such cells poorly predictive and irreproducible. We propose a new source of specialized endothelial cells based on cord blood circulating endothelial progenitors (EPCs). As prototype examples, we evaluated the capacity of EPCs to acquire properties characteristic of cerebral microvascular endothelial cells (blood-brain barrier (BBB)) or of arterial endothelial cells, in specific inducing culture conditions. Approach and Results First, we demonstrated that EPC-derived endothelial cells (EPDCs) co-cultured with astrocytes acquired several BBB phenotypic characteristics, such as restricted paracellular diffusion of hydrophilic solutes and the expression of tight junction proteins. Second, we observed that culture of the same EPDCs in a high concentration of VEGF resulted, through activation of Notch signaling, in an increase of expression of most arterial endothelial markers. Conclusions We have thus demonstrated that in vitro culture of early passage human cord blood EPDCs under specific conditions can induce phenotypic changes towards BBB or arterial phenotypes, indicating that these EPDCs maintain enough plasticity to acquire characteristics of a variety of specialized phenotypes. We propose that this property of EPDCs might be exploited for producing specialized endothelial cells in culture to be used for drug testing and predictive in vitro assays. PMID:24392113

  11. In Situ Tissue Engineering of Functional Small-Diameter Blood Vessels by Host Circulating Cells Only.

    PubMed

    Talacua, Hanna; Smits, Anthal I P M; Muylaert, Dimitri E P; van Rijswijk, Jan Willem; Vink, Aryan; Verhaar, Marianne C; Driessen-Mol, Anita; van Herwerden, Lex A; Bouten, Carlijn V C; Kluin, Jolanda; Baaijens, Frank P T

    2015-10-01

    Inflammation is a natural phase of the wound healing response, which can be harnessed for the in situ tissue engineering of small-diameter blood vessels using instructive, bioresorbable synthetic grafts. This process is dependent on colonization of the graft by host circulating cells and subsequent matrix formation. Typically, vascular regeneration in small animals is governed by transanastomotic cell ingrowth. However, this process is very rare in humans and hence less relevant for clinical translation. Therefore, a novel rat model was developed, in which cell ingrowth from the adjacent tissue is inhibited using Gore-Tex sheathing. Using this model, our aim here was to prove that functional blood vessels can be formed in situ through the host inflammatory response, specifically by blood-borne cells. The model was validated by implanting sex-mismatched aortic segments on either anastomoses of an electrospun poly(ɛ-caprolactone) (PCL) graft, filled with fibrin gel, into the rat abdominal aorta. Fluorescent in situ hybridization analysis revealed that after 1 and 3 months in vivo, over 90% of infiltrating cells originated from the bloodstream, confirming the effective shielding of transanastomotic cell ingrowth. Using the validated model, PCL/fibrin grafts were implanted, either or not loaded with monocyte chemotactic protein-1 (MCP-1), and cell infiltration and tissue development were investigated at various key time points in the healing cascade. A phased healing response was observed, initiated by a rapid influx of inflammatory cells, mediated by the local release of MCP-1. After 3 months in vivo, the grafts consisted of a medial layer with smooth muscle cells in an oriented collagen matrix, an intimal layer with elastin fibers, and confluent endothelium. This study proves the regenerative potential of cells in the circulatory system in the setting of in situ vascular tissue engineering. PMID:26200255

  12. Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget disease.

    PubMed

    Reddy, S V; Singer, F R; Mallette, L; Roodman, G D

    1996-11-01

    Paget disease of bone is characterized by abnormalities in all phases of bone remodeling, but the fundamental cellular abnormality resides in the osteoclast (OCL). Osteoclasts in bone involved by Paget disease contain viral-like nuclear and cytoplasmic inclusions that react with antibodies directed against paramyxovirus nucleocapsid proteins, such as measles virus, respiratory syncytial virus, or canine distemper virus. However, the identity of the virus or the mechanisms responsible for its persistence or pathologic role in Paget disease is unclear. Furthermore, although Paget disease persists for many years, it remains a highly localized process with new lesions rarely if ever developing in previously unaffected bones. Since osteoclasts are formed by fusion of mononuclear precursors derived from colony forming unit-granulocyte macrophage (CFU-GM), the granulocyte-macrophage progenitor, we used reverse transcriptase polymerase chain reaction (RT-PCR) analysis to determine if CFU-GM, more differentiated osteoclast precursors, and peripheral blood cells derived from CFU-GM express measles virus nucleocapsid (MV-N) transcripts. We found that osteoclast precursors, as well as peripheral blood mononuclear cells, express MV transcripts in 9 of 13 patients. Sequence analysis of the PCR amplified products confirmed nucleotide identity of MV-N transcripts expressed in peripheral blood and bone marrow-derived cells from the same patient. In contrast, MV-N transcripts were not detected in OCL precursors or the peripheral blood from 10 normal subjects. In situ hybridization studies using 35S-labeled antisense riboprobes to MV-N transcripts further confirmed the expression of MV transcripts in these cells. Sequence analysis of the PCR amplified product from one of these patients also identified a novel mutation that converted lysine441 to glutamic acid441 in the MV-N transcript. These data demonstrate that OCL precursors and circulating peripheral blood cells also express MV

  13. Exploring Secondary Students' Epistemological Features Depending on the Evaluation Levels of the Group Model on Blood Circulation

    ERIC Educational Resources Information Center

    Lee, Shinyoung; Kim, Heui-Baik

    2014-01-01

    The purpose of this study is to identify the epistemological features and model qualities depending on model evaluation levels and to explore the reasoning process behind high-level evaluation through small group interaction about blood circulation. Nine groups of three to four students in the eighth grade participated in the modeling practice.…

  14. Association between circulating blood or plasma urea nitrogen concentrations and reproductive efficiency in beef heifers and cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to examine the effect of circulating blood or plasma urea nitrogen concentrations (BPUNC) on reproductive efficiency in beef heifers and suckled beef cows. Data from nulliparous heifers (n = 284) as well as primiparous (n = 241) and multiparous (n = 806) beef cows were compiled ac...

  15. Determination of blood circulation times of superparamagnetic iron oxide nanoparticles by T2* relaxometry using ultrashort echo time (UTE) MRI.

    PubMed

    Scharlach, Constantin; Warmuth, Carsten; Schellenberger, Eyk

    2015-11-01

    Blood circulation is an important determinant of the biodistribution of superparamagnetic iron oxide nanoparticles. Here we present a magnetic resonance imaging (MRI) technique based on the use of ultrafast echo times (UTE) for the noninvasive determination of blood half-lives at high particle concentrations, when conventional pulse sequences fail to produce a useful MR signal. Four differently coated iron oxide nanoparticles were administered intravenously at a dose of 500 μmol Fe/kg bodyweight and UTE images of C57BL/6 mice were acquired on a 1-T ICON scanner (Bruker). T2* relaxometry was done by acquiring UTE images with echo times of 0.1, 0.8 and 1.6 ms. Blood circulation time was then determined by fitting an exponential curve to the time course of the measured relaxation rates. Circulation time was shortest for particles coated with malic acid (t1/2=23 min) and longest for particles coated with tartaric acid (t1/2=63 min). UTE-based T2* relaxometry allows noninvasive determination of blood circulation time and is especially useful when high particle concentrations are present.

  16. [Relationship between regulation effect of salvia miltiorrhiza on AQP2 in kidney and promoting blood circulation and diuresis].

    PubMed

    Dong, Xiao-Jing; Guo, Liang-Feng; Yao, Rui; Xue, Song-Yan; Li, Feng

    2014-08-01

    Partial nature of "promoting blood circulation and dieresis" of Salvia Miltiorrhizain was initially demonstrated by investigating the regulation effect of AQP2 expression in kidney of trauma blood stasis model rats with the Salvia Miltiorrhizain so as to provide guidance for its clinical deployment of administration. Random allocation was taken to averagely divide 30 SD rats into two groups: 10 rats in normal group and 20 rats in blood stasis syndrome group. Trauma blood stasis rat model was established by quantitatively beating. Then the rat model group was divided into model group and salvia group. After 7 days of treatment, the rat kidney AQP2 expression was detected, the content of urine AQP2 was compared and the damaged local muscle and kidney pathological changes were observed by immunohistochemical method and western blot method. Compared with that of the normal group, rats in model group had inflammatory cells infiltration, blood stasis and edema of the injured local muscles and up-regulated AQP2 expression, decreasing urinary output, and kidney tissues blood stasis and edema (P < 0.05). On the other hand, compared with that of the model group, those parameters of rats in salvia group were all decreasing except urine output (P < 0.05). Such result indicated that Salvia Miltiorrhiza can reduce trauma blood stasis rat content of urine AQP2 and down-regulated AQP2 expression in kidney tissue, so as to reduce the reabsorption of water by renal tubular and increase urine output. The promoting blood circulation effect of Salvia Miltiorrhizain can alleviate the degree of the damaged tissue edema and encourage urine drainage. This therapy is closely related to the effect of regulating AQP2 in kidney by salvia, so the purpose of this study by verifying "promoting blood circulation and diuresis" as the mechanism for the regulation effect of the salvia on AQP2 expression.

  17. Augmentation of blood circulation to the fingers by warming distant body areas

    NASA Technical Reports Server (NTRS)

    Koscheyev, V. S.; Leon, G. R.; Paul, S.; Tranchida, D.; Linder, I. V.

    2000-01-01

    Future activities in space will require greater periods of time in extreme environments in which the body periphery will be vulnerable to chilling. Maintaining the hands and fingers in comfortable conditions enhances finger flexibility and dexterity, and thus effects better work performance. We have evaluated the efficacy of promoting heat transfer and release by the extremities by increasing the blood flow to the periphery from more distant parts of the body. The experimental garment paradigm developed by the investigators was used to manipulate the temperature of different body areas. Six subjects, two females and four males, were evaluated in a stage-1 baseline condition, with the inlet temperature of the circulating water in the liquid cooling/warming garment (LCWG) at 33 degrees C. At stage 2 the total LCWG water inlet temperature was cooled to 8 degrees C, and at stage 3 the inlet water temperature in specific segments of the LCWG was warmed (according to protocol) to 45 degrees C, while the inlet temperature in the rest of the LCWG was maintained at 8 degrees C. The following four body-area-warming conditions were studied in separate sessions: (1) head, (2) upper torso/arm, (3) upper torso/arm/head, and (4) legs/feet. Skin temperature, heat flux and blood perfusion of the fingers, and subjective perception of thermal sensations and overall physical comfort were assessed. Finger temperature (T(fing)) analyses showed a statistically significant condition x stage interaction. Post-hoc comparisons (T(fing)) indicated that at stage 3, the upper torso/arm/head warming condition was significantly different from the head, upper torso/arm and legs/feet conditions, showing an increase in T(fing). There was a significant increase in blood perfusion in the fingers at stage 3 in all conditions. Subjective perception of hand warmth, and overall physical comfort level significantly increased in the stage 3 upper torso/arm/head condition. The findings indicate that

  18. Liver-derived matrix metalloproteinase-9 (gelatinase B) recruits progenitor cells from bone marrow into the blood circulation.

    PubMed

    Watanabe, Yoshifumi; Haruyama, Takahiro; Akaike, Toshihiro

    2003-04-01

    Matrix metalloproteinases (MMPs) are involved in invasive cell behavior, embryonic development and organ remodeling. In this report, we investigated the role of liver-derived MMP-9 in the in vivo system at liver injury. Liver injury induced MMP-9 expression in the liver 3 to 12 h after intravenous administration of anti-Fas antibody, followed by the expression of the activity and the protein detected by zymography and Western blotting, respectively, in the blood circulation. Interestingly, the MMP-9 expression was accompanied by the recruitment of hematopoietic progenitor cells from bone marrow into the circulation. The recruitment was blocked by a specific MMP-9 inhibitor, R94138, which did not affect the Fas-mediated liver injury or induced expression of MMP-9. Compulsive expression of mutant active MMP-9 in the liver also recruited the progenitor cells into the circulation. In contrast, partial hepatectomy, which treatment does not directly injure hepatocytes, did not recruit progenitor cells despite the increased expression of MMP-9 in the circulation. These results suggest that liver-derived MMP-9 induced by liver injury plays an essential role in the recruitment of hematopoietic progenitor cells from bone marrow into the blood circulation.

  19. Immunomagnetic Nano-Screening Chip for Circulating Tumor Cells Detection in Blood

    NASA Astrophysics Data System (ADS)

    Horton, A. P.; Lane, N.; Tam, J.; Sokolov, K.; Garner, H. R.; Uhr, J. W.; Zhang, X. J.

    2010-03-01

    We present a novel method towards diagnose cancer at an early stage via a blood test. Early diagnosis is high on the future agenda of oncologists because of significant evidence that it will result in a higher cure rate. Capture of circulating tumor cells (CTCs) which are known to escape from carcinomas at an early stage offers such an opportunity. We design, fabricate and optimize the nanomagnetic-screening chip that captures the CTCs in microfluid, and further integrate the nano-chip with the new multispectral imaging system so that it can quantify different tumor markers and automate the entire instrument. Specifically, hybrid plasmonic (Fe2O3-core Au shell) nanoparticles, conjugated a collection of antibodies especially chosen to target breast cancer CTCs, with high magnetic susceptibility will be used for effective immunomagnetic CTC isolation. Greatly increased sensitivity over previous attempts is demonstrated by decreasing the length scale for interactions between the magnetic-nanoparticle-tagged CTCs and the isolative magnetic field, while increasing the effective cross-sectional area over which this interaction takes place. The screening chip is integrated with a novel hyperspectral microscopic imaging (HMI) platform capable of recording the entire emission spectra in a single pass evaluation. The combined system will precisely quantify up to 10 tumor markers on CTCs.

  20. Polyethylene glycol-modified arachidyl chitosan-based nanoparticles for prolonged blood circulation of doxorubicin.

    PubMed

    Termsarasab, Ubonvan; Yoon, In-Soo; Park, Ju-Hwan; Moon, Hyun Tae; Cho, Hyun-Jong; Kim, Dae-Duk

    2014-04-10

    Doxorubicin (DOX)-loaded nanoparticles based on polyethylene glycol-conjugated chitosan oligosaccharide-arachidic acid (CSOAA-PEG) were explored for potential application to leukemia therapy. PEG was conjugated with CSOAA backbone via amide bond formation and the final product was verified by (1)H NMR analysis. Using the synthesized CSOAA-PEG, nanoparticles having characteristics of a 166-nm mean diameter, positive zeta potential, and spherical shape were produced for the delivery of DOX. The mean diameter of CSOAA-PEG nanoparticles in the serum solution (50% fetal bovine serum) remained relatively constant over 72 h as compared with CSOAA nanoparticles (changes of 20.92% and 223.16%, respectively). The sustained release pattern of DOX from CSOAA-PEG nanoparticles was displayed at physiological pH, and the release rate increased under the acidic pH conditions. The cytotoxicity of the CSOAA-PEG conjugate was negligible in human leukemia cells (K562) at the concentrations tested (∼ 100 μg/ml). The uptake rate of DOX from the nanoparticles by K562 cells was higher than that from the solution. Judging from the results of pharmacokinetic studies in rats, in vivo clearance rate of DOX from the CSOAA-PEG nanoparticle group was slower than other groups, subsequently extending the circulation period. The PEGylated CSOAA-based nanoparticles could represent an effective nano-sized delivery system for DOX which has been used for the treatment of blood malignancies.

  1. The history of the discovery of blood circulation: unrecognized contributions of Ayurveda masters.

    PubMed

    Patwardhan, Kishor

    2012-06-01

    Ayurveda, the native healthcare system of India, is a rich resource of well-documented ancient medical knowledge. Although the roots of this knowledge date back to the Vedic and post-Vedic eras, it is generally believed that a dedicated branch for healthcare was gradually established approximately between 400 BCE and 200 CE. Probably because the language of documentation of these early textbooks is in Sanskrit, a language that is not in day-to-day use among the general population even in India, many significant contributions of Ayurveda have remained unrecognized in the literature related to the history of medicine. In this communication, the discovery of blood circulation has been taken up as a case, and a few important references from the representative Ayurveda compendia that hint at a preliminary understanding of the cardiovascular system as a "closed circuit" and the heart acting as a pump have been reviewed. The central argument of this review is that these contributions from Ayurveda too must be recorded and credited when reviewing the milestones in the history of medicine, as Ayurveda can still possibly guide various streams of the current sciences, if revisited with this spirit.

  2. Optimized siRNA-PEG conjugates for extended blood circulation and reduced urine excretion in mice.

    PubMed

    Iversen, Frank; Yang, Chuanxu; Dagnæs-Hansen, Frederik; Schaffert, David H; Kjems, Jørgen; Gao, Shan

    2013-01-01

    Some of the main concerns with in vivo application of naked small interfering RNA are rapid degradation and urinary excretion resulting in a short plasma half-life. In this study we investigated how conjugation of polyethylene glycol (PEG) with variable chain length affects siRNA pharmacokinetics and biodistribution. The PEG chains were conjugated to chemically stabilized siRNA at the 5' terminal end of the passenger strand using click chemistry. The siRNA conjugate remained functionally active and showed significantly prolonged circulation in the blood stream after intravenous injection. siRNA conjugated with 20kDa PEG (PEG20k-siRNA) was most persistent, approximately 50% PEG20k-siRNA remained 1h post-injection, while the uncoupled siRNA was rapidly removed >90% at 15min. In vivo fluorescent imaging of the living animal showed increased concentration of siRNA in peripheral tissue and delayed urine excretion when coupled to PEG 20k. Biodistribution studies by northern blotting revealed equal distribution of conjugated siRNA in liver, kidney, spleen and lung without significant degradation 24 h post-injection. Our study demonstrates that PEG conjugated siRNA can be applied as a delivery system to improve siRNA bioavailability in vivo and may potentially increase the efficiency of siRNA in therapeutic applications.

  3. Comparison of different blood compartments for the detection of circulating DNA using a rat model of Pneumocystis pneumonia.

    PubMed

    Fréalle, E; Gantois, N; Aliouat-Denis, C M; Leroy, S; Zawadzki, C; Perkhofer, S; Aliouat, E M; Dei-Cas, E

    2015-09-01

    Pneumocystis is mostly found in the alveolar spaces, but circulation of viable organisms also occurs and suggests that the detection of DNA in blood could be used as a noninvasive procedure to improve the diagnosis of Pneumocystis pneumonia (PcP). In order to determine the optimal compartment for Pneumocystis DNA detection, we used a rat model of PcP and tested the presence of Pneumocystis with a quantitative mtLSU targeting real-time PCR in four blood compartments: whole blood, clot, serum and Platelet-Rich-Plasma (PRP). All samples from 4 Pneumocystis-free control rats were negative. Pneumocystis was detected in 79, 64, 57, and 57% of samples from 14 PcP rats, respectively, but DNA release was not related to pulmonary loads. These data confirm the potential usefulness of Pneumocystis DNA detection in the blood for PcP diagnosis and suggest that whole blood could be the most appropriate compartment for Pneumocystis detection.

  4. [Overview of clinical study on traditional Chinese medicine invigorating spleen and stomach, promoting blood circulation and remove blood stasis in treatment of chronic atrophic gastritis].

    PubMed

    Liu, Ming; Liu, Zhen

    2012-11-01

    In recent years, traditional Chinese medicines invigorating spleen and stomach, promoting blood circulation and removing blood stasis have made fruitful achievements in the treatment of chronic atrophic gastritis (CAG) and remarkable curative effects in eliminating clinical signs, enhancing the mucosal barrier, improving submucosal microcirculation, prompting submucosal atrophic glands and atypical hyperplasia reversal. This essay summarizes reports and literatures for clinical studies on CAG in recent years, and discusses its etiology, pathogenesis and clinical administration of traditional Chinese medicine and western medicine, in order to provide ideas and methods for CAG treatment with traditional Chinese medicines.

  5. Circulating MicroRNAs in maternal blood as potential biomarkers for fetal hypoxia in-utero.

    PubMed

    Whitehead, Clare L; Teh, Wan Tinn; Walker, Susan P; Leung, Cheryl; Larmour, Luke; Tong, Stephen

    2013-01-01

    Stillbirth affects 1 in 200 pregnancies and commonly arises due to a lack of oxygen supply to the fetus. Current tests to detect fetal hypoxia in-utero lack the sensitivity to identify many babies at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may serve as non-invasive biomarkers for pregnancy complications. In this study, we examined the expression of miRs known to be regulated by hypoxia in two clinical settings of significant fetal hypoxia: 1) labour and 2) fetal growth restriction. Six miRs (miR 210, miR 21, miR 424, miR 199a, miR 20b, and miR 373) were differentially expressed in pregnancies complicated by fetal hypoxia. In healthy term pregnancies there was a 4.2 fold increase in miR 210 (p<0.01), 2.7 fold increase in miR 424 (p<0.05), 2.6 fold increase in miR 199a (p<0.01) and 2.3 fold increase in miR 20b (p<0.05) from prior to labour to delivery of the fetus. Furthermore, the combined expression of miR 21 and miR 20b correlated with the degree of fetal hypoxia at birth determined by umbilical cord lactate delivery (r = 0.79, p = 0.03). In pregnancies complicated by severe preterm fetal growth restriction there was upregulation of the hypoxia-regulated miRs compared to gestation-matched controls: 3.6 fold in miR 210 (p<0.01), 3.6 fold in miR 424 (p<0.05), 5.9 fold in miR 21 (p<0.01), 3.8 fold in miR 199a (p<0.01) and 3.7 fold in miR 20b (p<0.01). Interestingly, the expression of miR 373 in gestation matched controls was very low, but was very highly expressed in FGR (p<0.0001). Furthermore, the expression increased in keeping with the degree of in-utero hypoxia estimated by fetal Doppler velocimetry. We conclude quantifying hypoxia-regulated miRs in the maternal blood may identify pregnancies at risk of fetal hypoxia, enabling early intervention to improve perinatal outcomes.

  6. Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors

    PubMed Central

    Chen, Ronald JY; Jinn, Tzyy-rong; Chen, Yi-ching; Chung, Tse-yu; Yang, Wei-hung; Tzen, Jason TC

    2011-01-01

    The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na+/K+-ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na+/K+-ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na+/K+-ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na+/K+-ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na+/K+-ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na+/K+-ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na+/K+-ATPase in the brain could be potential drugs for the treatment of ischemic stroke. PMID:21293466

  7. Active ingredients in Chinese medicines promoting blood circulation as Na+/K+ -ATPase inhibitors.

    PubMed

    Chen, Ronald J Y; Jinn, Tzyy-rong; Chen, Yi-ching; Chung, Tse-yu; Yang, Wei-hung; Tzen, Jason T C

    2011-02-01

    The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na(+)/K(+)-ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na(+)/K(+)-ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na(+)/K(+)-ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na(+)/K(+)-ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na(+)/K(+)-ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na(+)/K(+)-ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na(+)/K(+)-ATPase in the brain could be potential drugs for the treatment of ischemic stroke.

  8. [Researches of autonomic regulation of blood circulation in the condition of long-term space flight].

    PubMed

    Baevskiĭ, R M; Luchitskaia, E S; Funtova, I I; Chernikova, A G

    2013-01-01

    In the article is presented five-year experience of experimentation in autonomic regulation of blood circulation onboard the International space station. The heart rate variability (HRV) analysis was the basic methodical approach in the researches. We described probabilistic approach created on the basis of HRV analysis to an estimation of risk of pathology development in the conditions of long space flight. The individual type of autonomic regulation had essential value during the analysis of results. It is shown that the type of regulation, which is inherent in every cosmonaut in the conditions of weightlessness, remains even during following flights. We obtained the new scientific data on connection of character of adaptable reaction of an organism to the space flight factors with individual type of autonomic regulation. It is shown that staying in weightlessness is connected with changeover of regulatory systems and with transition in a zone of prenosological states. Adaptable reactions in weightlessness are characterized by tension growth of regulatory systems at preservation of sufficient functional reserves. The mobilization of additional resources after returning to the Earth is required and consequently functional reserve of mechanisms of regulation decreases. Cosmonauts with vagotonic and normo-sympatotonic types of autonomic regulation appear to be the most resistant. Knowing the type of autonomic regulation we will be able to foresee possible reaction of the cosmonaut to the factors of space flight. As a result of HRV analysis during the flight of the past few months likelihood estimations were calculated and risk categories were defined. Consequently, 3 groups of risk of pathology development were distinguished. In conclusion, theoretical and applied relevance of the conducted experiments were considered.

  9. Clinical Impact of MALDI-TOF MS Identification and Rapid Susceptibility Testing on Adequate Antimicrobial Treatment in Sepsis with Positive Blood Cultures

    PubMed Central

    Verroken, Alexia; Defourny, Lydwine; le Polain de Waroux, Olivier; Belkhir, Leïla; Laterre, Pierre-François; Delmée, Michel; Glupczynski, Youri

    2016-01-01

    Shortening the turn-around time (TAT) of positive blood culture (BC) identification (ID) and susceptibility results is essential to optimize antimicrobial treatment in patients with sepsis. We aimed to evaluate the impact on antimicrobial prescription of a modified workflow of positive BCs providing ID and partial susceptibility results for Enterobacteriaceae (EB), Pseudomonas aeruginosa and Staphylococcus aureus on the day of BC positivity detection. This study was divided into a pre-intervention period (P0) with a standard BC workflow followed by 2 intervention periods (P1, P2) with an identical modified workflow. ID was performed with MALDI-TOF MS from blood, on early or on overnight subcultures. According to ID results, rapid phenotypic assays were realized to detect third generation cephalosporin resistant EB/P. aeruginosa or methicillin resistant S. aureus. Results were transmitted to the antimicrobial stewardship team for patient’s treatment revision. Times to ID, to susceptibility results and to optimal antimicrobial treatment (OAT) were compared across the three study periods. Overall, 134, 112 and 154 positive BC episodes in P0, P1 and P2 respectively were included in the analysis. Mean time to ID (28.3 hours in P0) was reduced by 65.3% in P1 (10.2 hours) and 61.8% in P2 (10.8 hours). Mean time to complete susceptibility results was reduced by 27.5% in P1 and 27% in P2, with results obtained after 32.4 and 32.6 hours compared to 44.7 hours in P0. Rapid tests allowed partial susceptibility results to be obtained after a mean time of 11.8 hours in P1 and 11.7 hours in P2. Mean time to OAT was decreased to 21.6 hours in P1 and to 17.9 hours in P2 compared to 36.1 hours in P0. Reducing TAT of positive BC with MALDI-TOF MS ID and rapid susceptibility testing accelerated prescription of targeted antimicrobial treatment thereby potentially improving the patients’ clinical outcome. PMID:27228001

  10. Exploration of the effect and mechanism of activating blood circulation and stasis-removing therapy on tumor metastasis.

    PubMed

    Lu, Xiang; Li, Bai

    2009-10-01

    Metastasis is one of the specificities of late stage tumor and also a lethal factor often encountered. The study of tumor metastasis has important meaning for prolonging patients' survival and elevating their quality of life, but no really ideal prevention and treatment method has been found so far. Recent researches showed that tumor metastasis is correlated with platelet aggregation and blood hyperviscosity manner. Therefore, the early application of surgery, radiotherapy, chemotherapy and biological therapies, in combination with Chinese medicine therapy for activating blood circulation and removing stasis (ABCRS) may be, after all, an effective approach. ABCRS therapy is an important therapy of Chinese medicine, which, composed of several methods like smoothening blood flow in vessels, promoting blood circulation and dispersing stagnant blood, could influence tumor metastasis to different extents, and could coordinate with some other Chinese medicine therapeutic methods like supplementing qi, promoting qi, clearing heat, removing toxic substances, warming meridian, dispelling wind, eliminating dampness, nourishing yin, dissolving sputum, relieving stagnancy, emptying viscerals, etc. The effect and acting mechanism of ABCRS on tumor metastasis is summarized in this paper and its bi-directional regulatory effects discussed as well.

  11. [TREATMENT OF A NEWBORN BABIES FOR AN ACUTE DISORDER OF THE BRAIN BLOOD CIRCULATION OF A HEMORRHAGIC TYPE].

    PubMed

    Orlov, M Yu

    2015-10-01

    A timely and adequate application of complex of conservative and surgical measures determines at large the result of treatment of a newbor babies, suffering perinatal intracranial hematoma. The treatment includes, besides neurosurgical manipulations and operations, providing of evacuation of the blood extrused, the intracranial pressure normalization, liquorocirculation restoration, correction of hemodynamical and metabolic disorders, antiedematous, membrane-stabilizing and anticonvulsant therapy. A control of metabolic disorders, as well as especially hypoglycemia, hypocalcemia, hypomagnesemia, hypopyridoxinemia constitutes a leading moment of the treatment

  12. Results of the oxygen Fick method in a closed blood circulation model including "total arteriovenous diffusive shunt of oxygen".

    PubMed

    Ozbek, Mustafa; Akay, Ahmet

    2004-09-01

    It is considered that arteriovenous diffusive shunts of oxygen may cause inaccuracy of the oxygen Fick method as[Formula: see text] where[Formula: see text] is the pulmonary oxygen uptake,[Formula: see text] is the cardiac output, and CaO(2) and CvO(2) are the arterial and venous oxygen contents, respectively.A simple circulation model, including the whole circulation with nine well-mixed compartments (C1, ... C9), is constructed: the[Formula: see text] is assigned as constant as 6000 ml min(-1); the blood portions of 60 ml move at an interval of 600 ms. C1 and C2 compartments, each having 60 ml volume, represent the blood of pulmonary microcirculation, C3 represents the arterial blood with a volume of 1500 ml, C4, ..., C8, each also having a volume of 60 ml, represent the blood of peripheral microcirculation, whereas C9 represents the venous blood with a volume of 3000 ml. The pulmonary oxygen uptake[Formula: see text], related to C1 and C2, the oxygen release[Formula: see text], related to C4,...,C8, as well as a "total arteriovenous diffusive shunt of oxygen"[Formula: see text], from the arterial blood (C3) to the venous blood (C9), are calculated simultaneously. The alveolar gas has a constant oxygen partial pressure, and the pulmonary diffusion capacity is also constant; similar to modeling the pulmonry, oxygen diffusion, constant partial oxygen pressures for all peripheral tissues as well as constant diffusion capacities for all peripheral oxygen diffusion are also assigned. The diffusion capacities for the[Formula: see text] (between C3 and C9) are arbitrarily assigned.The Fick method gives incorrect results depending on the total arteriovenous diffusive shunt of oxygen[Formula: see text]. But the mechanism determining the magnitude of[Formula: see text] remains unclear.

  13. Elevation in Peripheral Blood Circulating Tumor Cell Number Correlates with Macroscopic Progression in UICC Stage IV Colorectal Cancer Patients

    PubMed Central

    Molnar, Bela; Floro, Lajos; Sipos, Ferenc; Toth, Bernadett; Sreter, Lydia; Tulassay, Zsolt

    2008-01-01

    Aims: Cytokeratin(CK) based real-time RT-PCR assays (QRT-PCR) are now available for peripheral blood circulating tumor cell (CTC) evaluations in colorectal cancer(CRC) patients. Results are non-existent for the application of these techniques to the determination of progression and therapy response in Dukes stage D CRC patients. Patients and methods: Each month 30 ml peripheral blood of 30 Dukes D patients (17 with progression) were drawn. CEA, CA19-9, CA72-A and TPA-M determinations were made. CK20, thymidilate synthase(TS) QRT-PCR was performed, as well. Buffy coat was used for immunmagnetic cancer cell isolation and CTC counting. Correlation between elevated CTC and macroscopic progression within 3 months was determined by Chi2 test. Results: Microscopic CTC single cell, doublet, cluster number were found in correlation with CK20 QRT-PCR results (p < 0.01). There was a significant increase in microscopic CTC number, CK20 and decrease in TS QRT-PCR levels (p < 0.05) in the peripheral blood of the non-responder as compared to responder patients. Elevation of the CTC was in significant correlation with macroscopic progression of the disease in 3 months (p < 0.01). Conclusions: CTC number reflects the chemotherapeutic sensitivity of CRC patients. Elevation of circulating tumor cell number in peripheral blood is in correlation with macroscopic progression. PMID:18334735

  14. Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice.

    PubMed

    Kim, Kyoohyun; Choe, Kibaek; Park, Inwon; Kim, Pilhan; Park, YongKeun

    2016-01-01

    Intravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mice were also investigated.

  15. Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice

    NASA Astrophysics Data System (ADS)

    Kim, Kyoohyun; Choe, Kibaek; Park, Inwon; Kim, Pilhan; Park, Yongkeun

    2016-09-01

    Intravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mice were also investigated.

  16. Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice

    PubMed Central

    Kim, Kyoohyun; Choe, Kibaek; Park, Inwon; Kim, Pilhan; Park, YongKeun

    2016-01-01

    Intravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mice were also investigated. PMID:27605489

  17. Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice.

    PubMed

    Kim, Kyoohyun; Choe, Kibaek; Park, Inwon; Kim, Pilhan; Park, YongKeun

    2016-01-01

    Intravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mice were also investigated. PMID:27605489

  18. Subtle exchange model of flow depended on the blood cell shape to enhance the micro-circulation in capillary

    NASA Astrophysics Data System (ADS)

    Chan, Iatneng

    2012-02-01

    In general the exchange of gases or other material in capillary system is conceptualized by the diffusion effect. But in this model, we investigate a micro-flow pattern by simulation and computation on a micro-exchange model in which the blood cell is a considered factor, especially on its shape. It shows that the cell benefits the circulation while it is moving in the capillary. In the study, the flow detail near the cell surface is mathematically analyzed, such that the Navier-Stokes equations are applied and the viscous factor is also briefly considered. For having a driven force to the motion of micro-circulation, a breathing mode is suggested to approximately compute on the flow rate in the blood capillary during the transfer of cell. The rate is also used to estimate the enhancement to the circulation in additional to the outcome of diffusion. Moreover in the research, the shape change of capillary wall under pressure influence is another element in the beginning calculation for the effect in the assistance to cell motion.

  19. Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters

    PubMed Central

    Yamada, Kana; Yokomaku, Kyoko; Haruki, Risa; Taguchi, Kazuaki; Nagao, Saori; Maruyama, Toru; Otagiri, Masaki; Komatsu, Teruyuki

    2016-01-01

    A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin‒albumin clusters (i) bearing four HSA units at the periphery (Hb-HSA4, large-size variant) and (ii) containing an intramolecularly crosslinked Hb in the center (XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior. PMID:26895315

  20. Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters.

    PubMed

    Yamada, Kana; Yokomaku, Kyoko; Haruki, Risa; Taguchi, Kazuaki; Nagao, Saori; Maruyama, Toru; Otagiri, Masaki; Komatsu, Teruyuki

    2016-01-01

    A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin‒albumin clusters (i) bearing four HSA units at the periphery (Hb-HSA4, large-size variant) and (ii) containing an intramolecularly crosslinked Hb in the center (XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior.

  1. Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures

    PubMed Central

    Madhavan, Dharanija; Cuk, Katarina; Burwinkel, Barbara; Yang, Rongxi

    2013-01-01

    In the recent years, circulating microRNAs (miRNAs) have garnered a lot of attention and interest in the field of disease biomarkers. With characteristics such as high stability, low cost, possibility of repeated sampling and minimal invasiveness, circulating miRNAs are ideal for development into diagnostic tests. There have been many studies reported on the potential of circulating miRNAs as early detection, prognostic, and predictive biomarkers in cancer. Here, we have reviewed the application of plasma and serum miRNAs as biomarkers for cancer focusing on epithelial carcinomas [prostate, breast, lung, colorectal, and gastric cancer (GC)] and hematological malignancies (leukemia and lymphoma). We have also addressed the common challenges that need to be overcome to achieve a successful bench to bedside transition. PMID:23802013

  2. From the discovery of the circulation of the blood to the first steps in hemorheology: part 2.

    PubMed

    Martins e Silva, J

    2009-12-01

    In the second and last part of this article, the contributions of two more brilliant figures are described in two sections, A and B, respectively Marcello Malpighi and Antonie van Leeuwenhoek. Through the originality of their work, both confirmed the pioneer William Harvey's observations and went on to add important details. Malpighi applied the optical microscope, until then used almost exclusively as a mere curiosity, to the in vitro study of the body tissues of various species. Outstanding among these pioneering observations was the visualization, for the first time, of capillary structures and blood corpuscles, on the basis of which he defined the composition of blood and, also for the first time, the concept of its fluidity. Furthermore, Malpighi confirmed the structural and functional continuity of the systemic circulation, which Harvey had been unable to demonstrate. Although van Leeuwenhoek lacked an academic education, he was able to see, through lenses he built himself, the microscopic details of the organic and inorganic world around him. Among numerous detailed observations of all types of substances, particularly important were the insights that he obtained into the nature of blood and red blood cells, to which he attributed the color of arterial and venous blood. He calculated the size of erythrocytes with striking accuracy. He was able to distinguish arterial from venous blood, confirmed the heart's function as the force behind the propulsion of the blood through the arteries and of the rhythmic nature of the pulse, and elucidated the return of the blood to the heart by different vessels, the veins. He visualized the bifurcation of the arteries into increasingly narrow vessels until they gave way to capillary networks, which in turn became successively wider venous channels. Van Leeuwenhoek demonstrated the existence of arterial-venous anastomoses. He discovered erythrocyte sedimentation and deformability (their shape varying from the original

  3. Elimination of young erythrocytes from blood circulation and altered erythropoietic patterns during paraquat induced anemic phase in mice.

    PubMed

    Bhardwaj, Nitin; Saxena, Rajiv K

    2014-01-01

    Paraquat a widely used herbicide causes a variety of toxic effects on humans and animals. The present study is focused on the interaction of paraquat with the mouse erythroid system. Administration of paraquat (10 mg/kg body weight i.p. on alternate days in C57Bl/6 mice) induced a significant fall in blood erythrocyte count on 7, 14, and 21 day time points but the erythrocyte count reverted back to normal by 28th day indicating the emergence of refractoriness to paraquat. A marked surge in the blood reticulocyte count was observed in paraquat treated mice that also subsided by 28th day. Young erythrocytes in circulation were randomly eliminated from blood circulation in paraquat treated mice and a significant elevation in the level of reactive oxygen species (ROS) was also observed maximally the erythrocytes of this age group. Cells representing various stages of erythroid differentiation in bone marrow and spleen were identified and enumerated flow cytometrically based on their expression of Ter119 and transferrin (CD71) receptor. Proliferative activity of erythroid cells, their relative proportion as well as their absolute numbers fell significantly in bone marrow of paraquat treated mice but all these parameters were significantly elevated in spleens of paraquat treated mice. These changes were essentially restricted to the cells belonging to the two earliest stages of erythroid differentiation. Taken together our results indicate that paraquat treatment causes a transient anemia in mice resulting from random elimination of young circulating erythrocytes as well as depressed erythropoietic activity in bone marrow. Spleen erythropoietic activity however was elevated in paraquat treated mice.

  4. [The comparative evaluation of tendencies in population mortality and particular characteristics of hospitalization under diseases of blood circulation system].

    PubMed

    Maksimova, T M; Belov, V B; Lushkina, N P

    2013-01-01

    The analysis of data bases established that in the Russian Federation population mortality of diseases of blood circulation system in toto and of main diseases included in this class (100-199 of ICD-10) is significantly higher than in European countries. The population mortality is determined both by morbidity and quality of medical care in case of development of disease. In Russia, the increase of number of cases of hospitalization per one patient passed away due to these causes. This indicator was lower in comparison with corresponding indicators characterizing levels of hospitalization in EU countries. In Russia, to decrease mortality of this pathology it is needed to extend indications for hospitalization.

  5. IBN NAFIS – A FORGOTTEN GENIUS IN THE DISCOVERY OF PULMONARY BLOOD CIRCULATION

    PubMed Central

    Akmal, M; Zulkifle, M; Ansari, AH

    2010-01-01

    Scientific theories take centuries to come into existence and they keep on evolving. Uncountable intellectual minds work on these theories; some fail to do anything about it; some add a little after tremendous efforts, and some people give remarkable and unforgettable contribution. As far as credit is concerned, the person who is able to prove the theory by his facts and who clears the maximum doubts by his observations, experimentations, facts and reasoning, gets the credit for that theory, and this should be done with honesty. The theory of pulmonary circulation took more than 2000 years to come into existence as we know it today. With the passage of time different people were given credit. Some say that it was given to Galen; some say it was Michael Servetus; others say that Realdus Columbus was the real discoverer; some gave the credit to Ibn Nafis, and finally people gave the credit to William Harvey. But after the rediscovery of Ibn Nafis’ manuscript no.62243 titled Sharah al Tashreeh al Qanoon, or “Commentary on the anatomy of Canon of Avicenna” in 1924 AD in Europe, it became clear that Ibn Nafis had described the pulmonary circulation almost 300 years before Harvey, and the historians like Aldo Mieli, Max Mayrhoff, Edward Coppola etc. clearly state that Ibn Nafis is the real discoverer of the pulmonary circulation and that he should be given the credit for the discovery of the pulmonary circulation. PMID:21042463

  6. A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages.

    PubMed

    Tibúrcio, Marta; Niang, Makhtar; Deplaine, Guillaume; Perrot, Sylvie; Bischoff, Emmanuel; Ndour, Papa Alioune; Silvestrini, Francesco; Khattab, Ayman; Milon, Geneviève; David, Peter H; Hardeman, Max; Vernick, Kenneth D; Sauerwein, Robert W; Preiser, Peter R; Mercereau-Puijalon, Odile; Buffet, Pierre; Alano, Pietro; Lavazec, Catherine

    2012-06-14

    Achievement of malaria elimination requires development of novel strategies interfering with parasite transmission, including targeting the parasite sexual stages (gametocytes). The formation of Plasmodium falciparum gametocytes in the human host takes several days during which immature gametocyte-infected erythrocytes (GIEs) sequester in host tissues. Only mature stage GIEs circulate in the peripheral blood, available to uptake by the Anopheles vector. Mechanisms underlying GIE sequestration and release in circulation are virtually unknown. We show here that mature GIEs are more deformable than immature stages using ektacytometry and microsphiltration methods, and that a switch in cellular deformability in the transition from immature to mature gametocytes is accompanied by the deassociation of parasite-derived STEVOR proteins from the infected erythrocyte membrane. We hypothesize that mechanical retention contributes to sequestration of immature GIEs and that regained deformability of mature gametocytes is associated with their release in the bloodstream and ability to circulate. These processes are proposed to play a key role in P falciparum gametocyte development in the host and to represent novel and unconventional targets for interfering with parasite transmission.

  7. Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice

    PubMed Central

    Imai, Takafumi; Takahashi, Yuki; Nishikawa, Makiya; Kato, Kana; Morishita, Masaki; Yamashita, Takuma; Matsumoto, Akihiro; Charoenviriyakul, Chonlada; Takakura, Yoshinobu

    2015-01-01

    Previous studies using B16BL6-derived exosomes labelled with gLuc–lactadherin (gLuc-LA), a fusion protein of Gaussia luciferase (a reporter protein) and lactadherin (an exosome-tropic protein), showed that the exosomes quickly disappeared from the systemic circulation after intravenous injection in mice. In the present study, the mechanism of rapid clearance of intravenously injected B16BL6 exosomes was investigated. gLuc-LA-labelled exosomes were obtained from supernatant of B16BL6 cells after transfection with a plasmid DNA encoding gLuc-LA. Labelling was stable when the exosomes were incubated in serum. By using B16BL6 exosomes labelled with PKH26, a lipophilic fluorescent dye, it was demonstrated that PKH26-labelled B16BL6 exosomes were taken up by macrophages in the liver and spleen but not in the lung, while PKH26-labelled exosomes were taken up by the endothelial cells in the lung. Subsequently, gLuc-LA-labelled B16BL6 exosomes were injected into macrophage-depleted mice prepared by injection with clodronate-containing liposomes. The clearance of the intravenously injected B16BL6 exosomes from the blood circulation was much slower in macrophage-depleted mice than that in untreated mice. These results indicate that macrophages play important roles in the clearance of intravenously injected B16BL6 exosomes from the systemic circulation. PMID:25669322

  8. [Isn't the heart the source of energy for blood circulation? "The heart doesn't know the basic laws of physics"].

    PubMed

    Papp, Lajos

    2008-08-01

    For hundreds of years, universal medical practice has depicted the heart to be the central organ, showing the heart's function as the primary source of energy for blood circulation, paying particular importance to the role of the heart valves. At present the generally accepted paradigm: the main force component of blood circulation is the pressure-gradient generated by the working heart. In serious combined illnesses of heart valves, the function of the valve is almost nonexistent. Based on the value of pressure in the chambers of the heart and in the great arteries and veins, blood flows from a place of high pressure to lower pressure, and should work the other way around as well. It is a fact, however, that even in such cases the circulation of blood is directed from the main arteries towards the veins: without the function of the valves--seemingly opposing the basic laws of physics--it keeps its original direction. Therefore we can justifiably infer that it isn't the work of the heart muscle that provides the source of energy for blood circulation. The heart has an essential function in the maintenance of blood circulation: pulse generation. The principal role of the heart is to generate pulses and not pressure.

  9. [Peculiarities of application of a cell saver apparatus in neonathal cardiosurgery using artificial blood circulation].

    PubMed

    Kuz'menko, S O; Chasovs'kyĭ, K S

    2015-01-01

    Elaborated and introduced into the practice method of the blood preservation, while correction of complex inborn heart failures (IHF) in a newborn babies, was proposed. It assumes application of system for intraoperative reinfusion of own erythrocytes with processing of residual perfusate and their reinfusion in a postperfusion period. Impact of the blood preservation on volume of a donor's blood components, hematological indices and methods of application of washed erythrocytes while correction of complex IHF in a newborn babies were presented. The method was applied in 47 newborn babies, to whom an arterial switch was performed for the main vessels transposition.

  10. [Indices of the responsiveness of system blood circulation as prognostic index of gastric ulcer development].

    PubMed

    Liutov, V V; Dergunov, A A; Liutov, R V

    2010-12-01

    118 patients with gastric ulcer and 112 healthy people (control set) were examined. It is established that determination of connections between phenotype, responsiveness of general circulation, variability of cardiac rhythm, types of personality and levels of reactive anxiety allows to diagnose not only the prenosological and initial forms of gastric ulcer, but also to determine the tactics of conservative and surgical treatment of this disease.

  11. Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

    SciTech Connect

    Otsuru, Satoru; Tamai, Katsuto . E-mail: tamai@gts.med.osaka-u.ac.jp; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

    2007-03-09

    Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood.

  12. Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation.

    PubMed

    Yamashita, Takuma; Takahashi, Yuki; Nishikawa, Makiya; Takakura, Yoshinobu

    2016-01-01

    Exosomes, which are expected to be delivery systems for biomolecules such as nucleic acids, are collected by several methods. However, the effect of exosome isolation methods on the characteristics of exosomes as drug carriers, such as recovery efficiency after sterile filtration and pharmacokinetics, has not been investigated despite the importance of these characteristics for the development of exosome-based delivery systems. In the present study, exosomes collected from murine melanoma B16-BL6 cells by several methods were compared with respect to dispersibility, recovery rate after filtering, and clearance from the blood circulation in mice. The exosomes were collected by three ultracentrifugation-based methods: simple ultracentrifugation/pelleting (pelleting method), ultracentrifugation with an iodixanol cushion (cushion method), and ultracentrifugation on an iodixanol density gradient (gradient method). The isolation methods had little effect on the particle number of exosomes. In contrast, transmission electron microscopy observation and size distribution measurement using tunable resistive pulse sensing indicated that the exosomes of the gradient method were more dispersed than the others. The exosomes were labeled with Gaussia luciferase and intravenously injected into mice. Clearance of injected exosomes from the blood circulation did not significantly change with isolation methods. When the exosomes were filtered using a 0.2-μm filter, the recovery rate was 82% for the exosomes of the gradient method, whereas it was less than 50% for the others. These results indicate that the exosome isolation method markedly affects the dispersibility and filtration efficiency of the exosomes. PMID:26545617

  13. Exploring Secondary Students' Epistemological Features Depending on the Evaluation Levels of the Group Model on Blood Circulation

    NASA Astrophysics Data System (ADS)

    Lee, Shinyoung; Kim, Heui-Baik

    2014-05-01

    The purpose of this study is to identify the epistemological features and model qualities depending on model evaluation levels and to explore the reasoning process behind high-level evaluation through small group interaction about blood circulation. Nine groups of three to four students in the eighth grade participated in the modeling practice. Their group models, which were represented by discourse and blood circulation diagrams, were analyzed for the development of the framework that informed the model evaluation levels and epistemological features. The model evaluation levels were categorized into levels one to four based on the following evaluation criteria: no evaluation, authoritative sources, superficial criteria, and more comprehensive criteria. The qualities of group models varied with the criteria of model evaluation. While students who used authoritative sources for evaluating the group model appeared to have an absolutist epistemology, students who evaluated according to the superficial criteria and more comprehensive criteria appeared to have an evaluative epistemology. Furthermore, groups with Level four showed a chain reaction of cognitive reasoning during the modeling practice concerning practical epistemology. The findings have implications for science teachers and education researchers who want to understand the context for developing students' practical epistemologies.

  14. Molecular biosensing mechanisms in the spleen for the removal of aged and damaged red cells from the blood circulation.

    PubMed

    Sugawara, Yoshiaki; Hayashi, Yuko; Shigemasa, Yuki; Abe, Yoko; Ohgushi, Ikumi; Ueno, Eriko; Shimamoto, Fumio

    2010-01-01

    Heinz bodies are intraerythrocytic inclusions of hemichrome formed as a result of hemoglobin (Hb) oxidation. They typically develop in aged red cells. Based on the hypothesis that hemichrome formation is an innate characteristic of physiologically normal Hb molecules, we present an overview of our previous findings regarding the molecular instability of Hb and the formation of hemichrome, as well as recent findings on Heinz body formation within normal human erythrocytes. Human adult Hb (HbO(2) A) prepared from healthy donors showed a tendency to produce hemichrome, even at close to physiological temperature and pH. Recent studies found that the number of Heinz bodies formed in red cells increased with increasing temperature when freshly drawn venous blood from healthy donors was subjected to mild heating above 37 °C. These findings suggest that Hb molecules control the removal of non-functional erythrocytes from the circulation via hemichrome formation and subsequent Heinz body clustering. In this review, we discuss the molecular biosensing mechanisms in the spleen, where hemichrome formation and subsequent Heinz body clustering within erythrocytes play a key role in the removal of aged and damaged red cells from the blood circulation.

  15. [Analysis and comparison of theories of circulation of blood and qi in both eastern and western ancient medicines].

    PubMed

    Wang, Tai

    2014-09-01

    In ancient Egypt, the theory of circulation of blood and qi was preliminarily established on the basis of cadaver dissection, gradually revised and improved following the progress of anatomy and physiology. However, the "Meridian Theory" of circulation of blood and qi in Chinese medicine had never been established on the basis of anatomical and physiological studies. Thus a suspicion was aroused, "whether the meridians really exist, or artificially assumed by imagination"? Therefore, in recent one half of a century, numerous scholars at home and abroad spent countless financial capacities and human power to study the essence of Meridians in order to find their material or substantial evidence, but with no breakthrough obtained. Nevertheless, in the 70th of the last century, studies on mechanisms of acupuncture analgesia and acupuncture anesthesia won an undoubtedly good result. Hence, the therapeutic effect of acupuncture on pain control was admitted by the "Consensus Statement on Acupuncture" at an international meeting held by NIH in Dec. 1997. Then the old Chinese acupuncture won an international acceptance and application. Therefore, the investigation of mechanism of acupuncture analgesia set up a positive model for future scientific researches on acupuncture mechanisms and essence of Meridians, as well as on other Chinese medical theories.

  16. Effects of pulsed electromagnetic fields on peripheral blood circulation in people with diabetes: A randomized controlled trial.

    PubMed

    Sun, Jiahui; Kwan, Rachel Lai-Chu; Zheng, Yongping; Cheing, Gladys Lai-Ying

    2016-07-01

    Cutaneous blood flow provides nourishment that plays an essential role in maintaining skin health. We examined the effects of pulsed electromagnetic fields (PEMFs) on cutaneous circulation of dorsal feet. Twenty-two patients with diabetes mellitus (DM) and 21 healthy control subjects were randomly allocated to receive either PEMFs or sham PEMFs (0.5 mT, 12 Hz, 30 min). Blood flow velocity and diameter of the small vein were examined by using ultrasound biomicroscopy; also, microcirculation at skin over the base of the 1st metatarsal bone (Flux1) and distal 1st phalange (Flux2) was measured by laser Doppler flowmetry before and after intervention. Results indicated that PEMFs produced significantly greater changes in blood flow velocity of the smallest observable vein than did sham PEMFs (both P < 0.05) in both types of subjects. However, no significant difference was found in changes of vein diameter, nor in Flux1 and Flux2, between PEMFs and sham PEMFs groups in subjects with or without DM. We hypothesized that PEMFs would increase blood flow velocity of the smallest observable vein in people with or without DM. Bioelectromagnetics. 37:290-297, 2016. © 2016 Wiley Periodicals, Inc.

  17. Do trichothecenes reduce viability of circulating blood cells and modify haemostasis parameters?

    PubMed

    Froquet, R; Arnold, F; Batina, P; Parent-Massin, D

    2003-01-01

    This manuscript describes the results of experiments conducted using human blood cells to determine the ability of T-2 toxin and DON to cause changes in clotting time, platelet aggregation, red blood cell haemolysis, RBC glucose content, lactate release, glutathione depletion, as well as white blood cell viability. In vitro results showed that haemostasis parameters and erythrocytes were not affected at concentrations able to induce inhibition of haematopoietic progenitor proliferation. In the presence of 10(-8) M and 10(-6) M T-2, the leucocyte number decreased at 24 h by 30% and 50% respectively. A 50% decrease in leucocyte number was observed for 10(-5) M DON. Results were compared with haematopoietic progenitor sensitivities. Due to the differences in sensitivities between mature blood cells and haematopoietic progenitors, haematological problems associated with trichothecene intoxication could be attributed to haematopoiesis inhibition.

  18. Mathematical Modelling of Cerebral Blood Circulation and Cerebral Autoregulation: Towards Preventing Intracranial Hemorrhages in Preterm Newborns

    PubMed Central

    Botkin, Nikolai; Alves-Pinto, Ana

    2014-01-01

    Impaired cerebral autoregulation leads to fluctuations in cerebral blood flow, which can be especially dangerous for immature brain of preterm newborns. In this paper, two mathematical models of cerebral autoregulation are discussed. The first one is an enhancement of a vascular model proposed by Piechnik et al. We extend this model by adding a polynomial dependence of the vascular radius on the arterial blood pressure and adjusting the polynomial coefficients to experimental data to gain the autoregulation behavior. Moreover, the inclusion of a Preisach hysteresis operator, simulating a hysteretic dependence of the cerebral blood flow on the arterial pressure, is tested. The second model couples the blood vessel system model by Piechnik et al. with an ordinary differential equation model of cerebral autoregulation by Ursino and Lodi. An optimal control setting is proposed for a simplified variant of this coupled model. The objective of the control is the maintenance of the autoregulatory function for a wider range of the arterial pressure. The control can be interpreted as the effect of a medicament changing the cerebral blood flow by, for example, dilation of blood vessels. Advanced numerical methods developed by the authors are applied for the numerical treatment of the control problem. PMID:25126111

  19. Mathematical modelling of cerebral blood circulation and cerebral autoregulation: towards preventing intracranial hemorrhages in preterm newborns.

    PubMed

    Lampe, Renée; Botkin, Nikolai; Turova, Varvara; Blumenstein, Tobias; Alves-Pinto, Ana

    2014-01-01

    Impaired cerebral autoregulation leads to fluctuations in cerebral blood flow, which can be especially dangerous for immature brain of preterm newborns. In this paper, two mathematical models of cerebral autoregulation are discussed. The first one is an enhancement of a vascular model proposed by Piechnik et al. We extend this model by adding a polynomial dependence of the vascular radius on the arterial blood pressure and adjusting the polynomial coefficients to experimental data to gain the autoregulation behavior. Moreover, the inclusion of a Preisach hysteresis operator, simulating a hysteretic dependence of the cerebral blood flow on the arterial pressure, is tested. The second model couples the blood vessel system model by Piechnik et al. with an ordinary differential equation model of cerebral autoregulation by Ursino and Lodi. An optimal control setting is proposed for a simplified variant of this coupled model. The objective of the control is the maintenance of the autoregulatory function for a wider range of the arterial pressure. The control can be interpreted as the effect of a medicament changing the cerebral blood flow by, for example, dilation of blood vessels. Advanced numerical methods developed by the authors are applied for the numerical treatment of the control problem.

  20. Ethanol Extract of Persimmon Tree Leaves Improves Blood Circulation and Lipid Metabolism in Rats Fed a High-Fat Diet

    PubMed Central

    Ryu, Ri; Kim, Hye-Jin; Moon, Byeongseok; Jung, Un Ju; Lee, Mi-Kyung; Lee, Dong Gun; Ryoo, ZaeYoung; Park, Yong Bok

    2015-01-01

    Abstract The leaves of the persimmon tree (PL) are known to have beneficial effects on hyperglycemia, dyslipidemia, and nonalcoholic fatty liver disease. We recently demonstrated that PL had antithrombotic properties in vitro. However, little is known about the antiplatelet and anticoagulant properties of PL in vivo. Omega-3 fatty acid (n-3 FA)-containing fish oil has been widely prescribed to improve blood circulation. This study compared the effects of dietary supplementation with an ethanol extract of PL or n-3 FA on blood coagulation, platelet activation, and lipid levels in vivo. Sprague–Dawley rats were fed a high-fat diet with either PL ethanol extract (0.5% w/w) or n-3 FA (2.5% w/w) for 9 weeks. Coagulation was examined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time. We examined plasma thromboxane B2 (TXB2), serotonin, and soluble P-selectin (sP-selectin) levels. The aPTT was significantly prolonged in the PL and n-3 FA supplement groups. PL also attenuated the TXB2 level and lowered arterial serotonin transporter mRNA expression, although it did not alter plasma serotonin or sP-selectin levels. C-reactive protein and leptin levels were significantly reduced by PL and n-3 FA supplementation. In addition, PL decreased plasma total- and low-density lipoprotein-cholesterol levels, as did n-3 FA treatment. These results indicated that the PL ethanol extract may have the potential to improve circulation by inhibiting blood coagulation and platelet activation and by reducing plasma cholesterol levels. PMID:26061228

  1. Ethanol Extract of Persimmon Tree Leaves Improves Blood Circulation and Lipid Metabolism in Rats Fed a High-Fat Diet.

    PubMed

    Ryu, Ri; Kim, Hye-Jin; Moon, Byeongseok; Jung, Un Ju; Lee, Mi-Kyung; Lee, Dong Gun; Ryoo, ZaeYoung; Park, Yong Bok; Choi, Myung-Sook

    2015-07-01

    The leaves of the persimmon tree (PL) are known to have beneficial effects on hyperglycemia, dyslipidemia, and nonalcoholic fatty liver disease. We recently demonstrated that PL had antithrombotic properties in vitro. However, little is known about the antiplatelet and anticoagulant properties of PL in vivo. Omega-3 fatty acid (n-3 FA)-containing fish oil has been widely prescribed to improve blood circulation. This study compared the effects of dietary supplementation with an ethanol extract of PL or n-3 FA on blood coagulation, platelet activation, and lipid levels in vivo. Sprague-Dawley rats were fed a high-fat diet with either PL ethanol extract (0.5% w/w) or n-3 FA (2.5% w/w) for 9 weeks. Coagulation was examined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time. We examined plasma thromboxane B2 (TXB2), serotonin, and soluble P-selectin (sP-selectin) levels. The aPTT was significantly prolonged in the PL and n-3 FA supplement groups. PL also attenuated the TXB2 level and lowered arterial serotonin transporter mRNA expression, although it did not alter plasma serotonin or sP-selectin levels. C-reactive protein and leptin levels were significantly reduced by PL and n-3 FA supplementation. In addition, PL decreased plasma total- and low-density lipoprotein-cholesterol levels, as did n-3 FA treatment. These results indicated that the PL ethanol extract may have the potential to improve circulation by inhibiting blood coagulation and platelet activation and by reducing plasma cholesterol levels. PMID:26061228

  2. Ethanol Extract of Persimmon Tree Leaves Improves Blood Circulation and Lipid Metabolism in Rats Fed a High-Fat Diet.

    PubMed

    Ryu, Ri; Kim, Hye-Jin; Moon, Byeongseok; Jung, Un Ju; Lee, Mi-Kyung; Lee, Dong Gun; Ryoo, ZaeYoung; Park, Yong Bok; Choi, Myung-Sook

    2015-07-01

    The leaves of the persimmon tree (PL) are known to have beneficial effects on hyperglycemia, dyslipidemia, and nonalcoholic fatty liver disease. We recently demonstrated that PL had antithrombotic properties in vitro. However, little is known about the antiplatelet and anticoagulant properties of PL in vivo. Omega-3 fatty acid (n-3 FA)-containing fish oil has been widely prescribed to improve blood circulation. This study compared the effects of dietary supplementation with an ethanol extract of PL or n-3 FA on blood coagulation, platelet activation, and lipid levels in vivo. Sprague-Dawley rats were fed a high-fat diet with either PL ethanol extract (0.5% w/w) or n-3 FA (2.5% w/w) for 9 weeks. Coagulation was examined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time. We examined plasma thromboxane B2 (TXB2), serotonin, and soluble P-selectin (sP-selectin) levels. The aPTT was significantly prolonged in the PL and n-3 FA supplement groups. PL also attenuated the TXB2 level and lowered arterial serotonin transporter mRNA expression, although it did not alter plasma serotonin or sP-selectin levels. C-reactive protein and leptin levels were significantly reduced by PL and n-3 FA supplementation. In addition, PL decreased plasma total- and low-density lipoprotein-cholesterol levels, as did n-3 FA treatment. These results indicated that the PL ethanol extract may have the potential to improve circulation by inhibiting blood coagulation and platelet activation and by reducing plasma cholesterol levels.

  3. Lung Circulation.

    PubMed

    Suresh, Karthik; Shimoda, Larissa A

    2016-04-01

    The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed. PMID:27065170

  4. Low frequency components of the body's center of gravity and blood circulation.

    PubMed

    Inamura, K; Mano, T; Iwase, S; Amagishi, Y; Aoki, K

    1991-01-01

    The purpose of this study was to clarify how low frequency components of the body's center of gravity, mainly 1 minute waves (1-MWs), are related to the mechanism of compensation for the venous blood pooling in the legs during static standing in humans. The 1-MWs of foot pressure center, oscillations of body circumferences and other parameters were analyzed with cross-power spectral analysis. The 1-MW of the calf's blood volume propagated to the chest via the venous system. This was inversely synchronized with the 1-MW of the body's center of gravity. It was speculated that muscular pumping of the calf related to the 1-MW of the body's center of gravity might be compensating for the venous blood pooling in the legs.

  5. Innovative Strategy in Treating Angina Pectoris with Chinese Patent Medicines by Promoting Blood Circulation and Removing Blood Stasis: Experience from Combination Therapy in Chinese Medicine.

    PubMed

    Xiong, Xing-Jiang; Wang, Zhong; Wang, Jie

    2015-01-01

    Coronary heart disease (CHD) is one of the leading causes of death worldwide. Moreover, angina pectoris is one of the most important types of CHD. Therefore, prevention and effective treatment of angina pectoris is of utmost importance in both China and western countries. However, undesirable effects of antianginal therapy do influence treatment adherence to a certain extent. Therefore, it's not surprising that, complementary and alternative medicine (CAM), including Chinese medicine (CM), are widely welcomed among patients with CHD, hoping that it might complement western medicine. In our previous studies, blood stasis syndrome (BSS) (Xueyu Zheng) was the main syndrome (Zheng-hou) of angina pectoris. Currently, China Food and Drug Administration authoritatively recommended more than 200 Chinese patent medicines (CPMs) as complementary or adjunctive therapies for symptom management and enhancing quality of life along with mainstream care on angina pectoris management in mainland China. This paper reviewed 4 kinds of most frequently-used CPMs by promoting blood circulation and removing blood stasis in the treatment of angina pectoris. It aims to evaluate the current evidence of CPMs in combination therapy for angina pectoris. This review indicated that CPMs as adjunctive treatment to routine antianginal therapy play an active role in reducing the incidence of primary endpoint events, decreasing anginal attack rate, and improving electrocardiogram. Additionally, CPMs have been proven relatively safe. Further rigorously designed clinical trials should be conducted to confirm the results.

  6. Prolonged Blood Circulation and Enhanced Tumor Accumulation of Folate-Targeted Dendrimer-Polymer Hybrid Nanoparticles

    PubMed Central

    Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel; Burdette, Joanna E.; Hong, Seungpyo

    2014-01-01

    Nanoparticle (NP)-based drug delivery platforms have received a great deal of attention over the past two decades for their potential in targeted cancer therapies. Despite the promises, passive targeting approaches utilizing relatively larger NPs (typically 50–200 nm in diameter) allow for passive tumor accumulation, but hinder efficient intratumoral penetration. Conversely, smaller, actively targeted NPs (<20 nm in diameter) penetrate well into the tumor mass, but are limited by their rapid systemic elimination. To overcome these limitations, we have designed a multi-scale hybrid NP platform that loads smaller poly(amidoamine) (PAMAM) dendrimers (~5 nm in diameter) into larger poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) NPs (~70 nm). A biodistribution study in healthy mice revealed that the hybrid NPs circulated longer than free dendrimers and were mostly cleared by macrophages in the liver and spleen, similar to the in vivo behavior of PEG-PLA NPs. When injected intravenously into the BALB/c athymic nude mice bearing folate receptor (FR)-overexpressing KB xenograft, the targeted hybrid NPs encapsulating folate (FA)-targeted dendrimers achieved longer plasma circulation than free dendrimers and higher tumor concentrations than both free dendrimers and the empty PEG-PLA NPs. These results suggest that the hybrid NPs successfully combine the in vivo advantages of dendrimers and polymeric NPs, demonstrating their potential as a new, modular platform for drug delivery. PMID:24837188

  7. Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clinical trials using cholesteryl ester transfer protein (CETP) inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. We evaluated the relations of baseline plasma CETP activity and longitudinal BP change. One tho...

  8. Low toxicity and long circulation time of Polyampholyte-coated magnetic nanoparticles for blood pool contrast agents

    PubMed Central

    Wang, Qi; Shen, Ming; Zhao, Tao; Xu, Yuanyuan; Lin, Jiang; Duan, Yourong; Gu, Hongchen

    2015-01-01

    Polyampholyte-coated (poly(acrylic acid) (PAA)-co-3-(diethylamino)-propylamine (DEAPA)) magnetite nanoparticles (PAMNPs) have been prepared as contrasting agent used in magnetic resonance imaging (MRI). Excellent biocompatibility is required for contrasting agents used in high-resolution magnetic resonance angiography. To evaluate the biocompatibility of PAMNPs, some experiments have been conducted. The hemolysis, plasma recalcification, dynamic blood clotting, prothrombin time, inflammatory cytokine release and complement system activation assays were carried out to investigate the hemocompatibility. To evaluate the toxicity to vessel, MTT test and vascular irritation tests were conducted. Tissue toxicity test was also performed to investigate the biocompability in vivo. We also looked into the biodistribution. The results showed that PAMNPs at the working concentration (0.138 mM) present similar hemocompatibility with negative control, thus have no significant effect to vessels. PAMNPs were mainly distributed in the liver and the blood. The circulation time in blood was considerably long, with the half-time of 3.77 h in plasma. This property is advantageous for PAMNPs' use in angiography. PAMNPs could be metabolized rapidly in mice and were not observed to cause any toxic or adverse effect. In short, these results suggest that the PAMNPs have great potential to serve as safe contrast agents in magnetic resonance imaging (MRI). PMID:25585607

  9. Low toxicity and long circulation time of Polyampholyte-coated magnetic nanoparticles for blood pool contrast agents

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Shen, Ming; Zhao, Tao; Xu, Yuanyuan; Lin, Jiang; Duan, Yourong; Gu, Hongchen

    2015-01-01

    Polyampholyte-coated (poly(acrylic acid) (PAA)-co-3-(diethylamino)-propylamine (DEAPA)) magnetite nanoparticles (PAMNPs) have been prepared as contrasting agent used in magnetic resonance imaging (MRI). Excellent biocompatibility is required for contrasting agents used in high-resolution magnetic resonance angiography. To evaluate the biocompatibility of PAMNPs, some experiments have been conducted. The hemolysis, plasma recalcification, dynamic blood clotting, prothrombin time, inflammatory cytokine release and complement system activation assays were carried out to investigate the hemocompatibility. To evaluate the toxicity to vessel, MTT test and vascular irritation tests were conducted. Tissue toxicity test was also performed to investigate the biocompability in vivo. We also looked into the biodistribution. The results showed that PAMNPs at the working concentration (0.138 mM) present similar hemocompatibility with negative control, thus have no significant effect to vessels. PAMNPs were mainly distributed in the liver and the blood. The circulation time in blood was considerably long, with the half-time of 3.77 h in plasma. This property is advantageous for PAMNPs' use in angiography. PAMNPs could be metabolized rapidly in mice and were not observed to cause any toxic or adverse effect. In short, these results suggest that the PAMNPs have great potential to serve as safe contrast agents in magnetic resonance imaging (MRI).

  10. Enhancement of Capture Sensitivity for Circulating Tumor Cells in a Breast Cancer Patient's Blood by Silicon Nanowire Platform.

    PubMed

    Kim, Dong-Joo; Choi, Mun-Ki; Jeong, Jin-Tak; Lim, Jung-Taek; Lee, Han-Byoel; Han, Wonshik; Lee, Sang-Kwon

    2016-04-01

    The separation of circulating tumor cells (CTCs) from the blood of cancer patients with high sensitivity is an essential technique for selecting chemotherapeutic agents at a patient-by-patient level. Recently, various research groups have reported a nanostructure-based platform for rare cell capture due to its high surface area and 3D nanotopographic features. However, evaluation of capture sensitivity based on chemical modification of the nanostructure surface has not yet been performed. Here, we evaluated the capture sensitivity for CTCs from the blood of three patients diagnosed with stage IV metastatic breast cancer by using the following three platforms: streptavidin-conjugated silicon nanowire (STR-SiNW), poly-l-lysine-coated silicon nanowire (PLL-SiNW), and poly-l-lysine-coated glass (PLL-glass). The number of evaluated CTCs on STR-SiNW, PLL-SiNW, and PLL-glass were 16.2 ± 5.5 cells, 7.3 ± 2.9 cells, and 4.7 ± 1.5 cells, respectively, per 0.5 ml. Therefore, we suggest that the STR-SiNW platform is highly adaptable for the quantitative evaluation of CTCs from the blood of cancer patients in the clinical setting.

  11. Blood circulation and tissue biodistribution of lipid--quantum dot (L-QD) hybrid vesicles intravenously administered in mice.

    PubMed

    Al-Jamal, Wafa' T; Al-Jamal, Khuloud T; Cakebread, Andrew; Halket, John M; Kostarelos, Kostas

    2009-09-01

    The present work describes the pharmacokinetics of recently developed liposome-quantum dot (L-QD) hybrid vesicles in nude mice following systemic administration. Hydrophobic QD were incorporated into different bilayer compositions, and the serum stability of such hybrid vesicles was evaluated using turbidity and carboxyfluorescein release measurements. L-QD hybrid blood profile and organ biodistribution were also determined by elemental (cadmium) analysis. Following intravenous administration, different tissue biodistribution profiles and tissue affinities were observed depending on the L-QD lipid bilayer characteristics. Immediate blood clearance was observed with cationic (DOTAP/DOPE/Chol) hybrid with rapid lung accumulation, while incorporation of PEG at the surface of zwitterionic vesicles dramatically prolonged their blood circulation half-life after systemic administration. Overall, the L-QD hybrid vesicle system is considered a viable platform that allows QD delivery to different tissues through facile modulation of the hybrid vesicle characteristics. In addition, L-QD offers many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.

  12. [Blood circulation features by treatment of multiply mandible fractures by means of transosseus osteosynthesis].

    PubMed

    Krasnov, V V; Kononovich, N A

    2013-01-01

    The multiple injury of the mandible was modeled experimentally in 27 adult mongrel dogs with subsequent fixation using a device for transosseous osteosynthesis. The special features of soft tissue hemodynamics in the injury zone and contralateral symmetrical part were studied. It has been determined that the unidirectional changes in functional properties of the arterial bed vessels occur under the conditions created, and these changes are more marked on the injury side and characterized by vasodilatation. Circulation in the injury zone doesn't recover by the end of fixation. Performing the measures directed for the improvement of vascular elastotonic properties during mandibular fracture treatment will allow to decrease the degree of hemodynamics disorders in paraosseous tissues, as well as will have a positive effect on a final clinical outcome.

  13. Computerized capillaroscopy as a visualization channel for lipid quantification in circulating blood

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Youri I.; Ishunina, Angela M.; Ovsyannickov, Konstantin V.

    2001-06-01

    There are correspondences between the number of lipid inclusions as detected with computerized capillaroscopy and the lipid parameters as determined using a routing blood test. The results have been obtained in the course of a study of two healthy volunteer groups (n equals 24) and three groups of patients: those suffering from ischemic heart disease with myocardial infarction in their past and heart failure (n equals 13), complicated insulin-independent diabetics (n equals 58), and patients with uncomplicated insulin-independent diabetes (n equals 27). Neither of the healthy volunteers had small lipid inclusions in the blood on an empty stomach. Moreover, lipid exchange parameters of every healthy volunteer as measured in a routine test were within the acceptable limits, while in patients with diabetes as well as in patients with coronary artery disease complicated by heart failure who had high cholesterol level, an elevated number of lipid inclusions was observed.

  14. [Oral status and oral mucosa blood circulation changes in patients with chronic heart failure].

    PubMed

    Orekhova, L Iu; Rybakova, M G; Barmasheva, A A; Kuznetsova, I A; Semernin, E N; Shirshova, N A; Shliakhto, E V; Gudkova, A Ia

    2013-01-01

    The objective of this study was to characterize dental status and oral mucosa blood flow in patients with chronic heart failure and amyloid deposits in oral mucosa. Histological and immunohistochemical analysis of 80 oral mucosa biopsies taken from patients aged 32-72 years with chronic heart failure I-IV NYHA functional class was carried out. It detected a systemic amyloidosis in 15.7% of cases; a local amyloid deposition in oral mucosa was found in 58.5% of cases. Amyloid deposition in oral mucosa was associated with severe chronic generalized periodontitis in more than a half of cases. Amyloid deposits in oral mucosa were revealed more often in patients with metabolic syndrome (63.5%). The article describes dental status and oral mucosa blood flow in patients with heart failure.

  15. Blood circulation in rat lungs under conditions of reduced oxygen level in inhaled air.

    PubMed

    Ivanov, K P; Mel'nikova, N N

    2012-12-01

    According to some authors, reduction in oxygen level in the lung alveoli results in constriction of afferent vessels, while others observed no vessel constriction. The issue is of principle importance in relation to the lung involvement in body adaptation to hypoxia. Conventional methods are inefficient to solve it, therefore we used a contact microscope allowing observation of lung circulatory system structure and condition of the lung circulatory system in whole, virtually intact animal, on whole undamaged lungs in situ, at normal physiological lung position in the thorax. We found that large vessels carrying blood to the alveoli do not constrict or dilate at reduced Po(2)in lung alveoli. These vessels with a diameter of 15 to 40 μ and more are the only blood source for alveoli.

  16. Molecular detection of peripheral blood breast cancer mRNA transcripts as a surrogate biomarker for circulating tumor cells.

    PubMed

    Lasa, Adriana; Garcia, Arnal; Alonso, Carmen; Millet, Pilar; Cornet, Mónica; Ramón y Cajal, Teresa; Baiget, Montserrat; Barnadas, Agusti

    2013-01-01

    Circulating tumor cells (CTCs) are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR) using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20) performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.

  17. Changes in blood circulation in teeth and supporting tissues incident to experimental tooth movement.

    PubMed

    Vandevska-Radunovic, V; Kristiansen, A B; Heyeraas, K J; Kvinnsland, S

    1994-10-01

    Fluorescent microspheres (FM) were used to semi-quantify the effect of orthodontic forces on blood flow in oral tissues in young rats. Forty-five animals had an orthodontic appliance inserted on the first maxillary molar on one side exerting a mesial force of approximately 50 g. Ten animals served as unoperated controls. On days 1, 3, 7, 14, and 21 after the start of the experiment, FM were injected into the left ventricle through an abdominal approach in the experimental and control animals. FM were counted in serial sections from the jaws in the periodontal ligament, pulp, and alveolar bone in a fluorescent microscope. The number of FM per tissue volume and/or tissue weight was taken as a measure of blood flow. The experimental side had significantly lower numbers of FM/mm3 in the periodontal ligament of the first and the second molar on the first day, compared with the contralateral side. However, a steady, significant increase in the number of FM/mm3 in the periodontal and pulpal tissues, and FM/mg in the alveolar bone could be observed on the third and seventh days on the experimental side of the first, second, and third molars compared with the contralateral side, while in the later stages the values of the two sides approached each other. The results of this study indicate that a localized experimental tooth movement initiates a more generalized blood flow response in the periodontal ligament, dental pulp and alveolar bone.

  18. Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles

    NASA Astrophysics Data System (ADS)

    Hadjidemetriou, Marilena; Al-Ahmady, Zahraa; Kostarelos, Kostas

    2016-03-01

    Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the `protein corona' and it is considered to be a determinant factor for the pharmacological, toxicological and therapeutic profile of NPs. Protein exposure time is thought to greatly influence the composition of protein corona, however the dynamics of protein interactions under realistic, in vivo conditions remain unexplored. The aim of this study was to quantitatively and qualitatively investigate the time evolution of in vivo protein corona, formed onto blood circulating, clinically used, PEGylated liposomal doxorubicin. Protein adsorption profiles were determined 10 min, 1 h and 3 h post-injection of liposomes into CD-1 mice. The results demonstrated that a complex protein corona was formed as early as 10 min post-injection. Even though the total amount of protein adsorbed did not significantly change over time, the fluctuation of protein abundances observed indicated highly dynamic protein binding kinetics.Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the `protein corona' and it is considered to be a determinant factor for the pharmacological, toxicological and therapeutic profile of NPs. Protein exposure time is thought to greatly influence the composition of protein corona, however the dynamics of protein interactions under realistic, in vivo conditions remain unexplored. The aim of this study was to quantitatively and qualitatively investigate the time evolution of in vivo protein corona, formed onto blood circulating, clinically used, PEGylated liposomal doxorubicin. Protein adsorption profiles were determined 10 min, 1 h and 3 h post

  19. Active compounds in Chinese herbs and medicinal animal products which promote blood circulation via inhibition of Na+, K+-ATPase.

    PubMed

    Tzen, Jason Tc; Chen, Ronald Jy; Chung, Tse-Yu; Chen, Yi-Ching; Lin, Nan-Hei

    2010-01-01

    The therapeutic effect of cardiac glycosides for congestive heart failure lies in their reversible inhibition on Na+, K+-ATPase located in human myocardium. Several steroid-like compounds containing a core structure similar to cardiac glycosides have been found in many Chinese herbs and medicinal animal products conventionally used to promote blood circulation. They are putatively responsible for the therapeutic effect of those medicinal products via the same mechanism of inhibiting Na+, K+-ATPase. Inhibitory potency on Na+, K+-ATPase by ginsenosides, one of the identified steroid-like compounds, is significantly affected by sugar attachment that might cause steric hindrance of their binding to Na+, K+-ATPase. Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, substantially inhibit Na+, K+-ATPase. However, their inhibitory potency is abolished when sugar moieties are linked to the C-6 or C-20 position of the steroid-like structure. In contrast, no appreciable contents of steroid-like compounds are found in danshen, a well-known Chinese herb traditionally regarded as an effective medicine promoting blood circulation. Instead, magnesium lithospermate B (MLB), the major soluble ingredient in danshen, is assumed to be responsible for the therapeutic effect by inhibiting Na+, K+-ATPase in a manner comparable to cardiac glycosides. Neuroprotective effects of cardiac glycosides, ginsenosides and MLB against ischemic stroke were accordingly observed in a cortical brain slice-based assay model. Whether the neuroprotection is also triggered by inhibition of Na+, K+-ATPase remains to be investigated. Molecular modeling suggests that cardiac glycosides, ginsenosides and MLB presumably bind to the same extracellular pocket of the Na+, K+-ATPase alpha subunit. PMID:20438664

  20. Active compounds in Chinese herbs and medicinal animal products which promote blood circulation via inhibition of Na+, K+-ATPase.

    PubMed

    Tzen, Jason Tc; Chen, Ronald Jy; Chung, Tse-Yu; Chen, Yi-Ching; Lin, Nan-Hei

    2010-01-01

    The therapeutic effect of cardiac glycosides for congestive heart failure lies in their reversible inhibition on Na+, K+-ATPase located in human myocardium. Several steroid-like compounds containing a core structure similar to cardiac glycosides have been found in many Chinese herbs and medicinal animal products conventionally used to promote blood circulation. They are putatively responsible for the therapeutic effect of those medicinal products via the same mechanism of inhibiting Na+, K+-ATPase. Inhibitory potency on Na+, K+-ATPase by ginsenosides, one of the identified steroid-like compounds, is significantly affected by sugar attachment that might cause steric hindrance of their binding to Na+, K+-ATPase. Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, substantially inhibit Na+, K+-ATPase. However, their inhibitory potency is abolished when sugar moieties are linked to the C-6 or C-20 position of the steroid-like structure. In contrast, no appreciable contents of steroid-like compounds are found in danshen, a well-known Chinese herb traditionally regarded as an effective medicine promoting blood circulation. Instead, magnesium lithospermate B (MLB), the major soluble ingredient in danshen, is assumed to be responsible for the therapeutic effect by inhibiting Na+, K+-ATPase in a manner comparable to cardiac glycosides. Neuroprotective effects of cardiac glycosides, ginsenosides and MLB against ischemic stroke were accordingly observed in a cortical brain slice-based assay model. Whether the neuroprotection is also triggered by inhibition of Na+, K+-ATPase remains to be investigated. Molecular modeling suggests that cardiac glycosides, ginsenosides and MLB presumably bind to the same extracellular pocket of the Na+, K+-ATPase alpha subunit.

  1. In vivo multispectral photoacoustic and photothermal flow cytometry with multicolor dyes: a potential for real-time assessment of circulation, dye-cell interaction, and blood volume

    PubMed Central

    Proskurnin, Mikhail A.; Zhidkova, Tatyana V.; Volkov, Dmitry S.; Sarimollaoglu, Mustafa; Galanzha, Ekaterina I.; Mock, Donald; Zharov, Vladimir P.

    2011-01-01

    Recently, photoacoustic (PA) flow cytometry (PAFC) has been developed for in vivo detection of circulating tumor cells and bacteria targeted by nanoparticles. Here, we propose multispectral PAFC with multiple dyes having distinctive absorption spectra as multicolor PA contrast agents. As a first step of our proof-of-concept, we characterized high-speed PAFC capability to monitor the clearance of three dyes (ICG, MB, and TB) in an animal model in vivo and in real time. We observed strong dynamic PA signal fluctuations, which can be associated with interactions of dyes with circulating blood cells and plasma proteins. PAFC demonstrated enumeration of circulating red and white blood cells labeled with ICG and MB, respectively, and detection of rare dead cells uptaking TB directly in bloodstream. The possibility for accurate measurements of various dye concentrations including CV and BG were verified in vitro using complementary to PAFC photothermal (PT) technique and spectrophotometry under batch and flow conditions. We further analyze the potential of integrated PAFC/PT spectroscopy with multiple dyes for rapid and accurate measurements of circulating blood volume without a priori information on hemoglobin content, which is impossible with existing optical techniques. This is important in many medical conditions including surgery and trauma with extensive blood loss, rapid fluid administration, transfusion of red blood cells. The potential for developing a robust clinical PAFC prototype that is, safe for human, and its applications for studying the liver function are further highlighted. PMID:21905207

  2. [Effect of dihydroergotamine on blood circulation in man in conditions of orthostasis].

    PubMed

    Modin, A Iu; Abrosimov, S V; Anashkin, O D; Zhidkov, V V; Lobachik, V I

    1984-01-01

    The physiological effects of zero-g were simulated by 6-hour antiorthostatic hypokinesia at -15 degrees, using eight healthy volunteers. They took part in two experimental runs at a 2 week interval. During the first study the test subjects received a placebo and during the second study they got 6 mg dihydroergotamine methane sulfonate per os. Radiometric examinations of the whole body and its compartments (head, chest, abdomen, legs) showed that the drug increased blood pooling in the upper body and decreased it in the lower body at every position of the long axis of the body relative to the gravity vector.

  3. [Some disorder features of blood circulation in lungs in older age influenza patients].

    PubMed

    Roganova, I V

    2011-01-01

    Patients aged 51-65 years with influenza develop circulatory disorders of the lung. Tone of the arteries of small and medium-caliber and venular vessels of the vascular bed of the lungs persistently reduced during the illness and a month after its start. The flow of venous blood from the vessels of the lungs disturbs: it is slow, difficult and becomes unstable. Such circulatory disorders in the lungs of influenza patients of older age groups appear during the illness and persist for a long time in the recovery period, which is a risk factor associated with complications of the respiratory system, not only during the illness, but after the disease.

  4. Methylated circulating tumor DNA in blood: power in cancer prognosis and response

    PubMed Central

    Warton, Kristina; Mahon, Kate L; Samimi, Goli

    2016-01-01

    Circulating tumor DNA (ctDNA) in the plasma or serum of cancer patients provides an opportunity for non-invasive sampling of tumor DNA. This ‘liquid biopsy’ allows for interrogations of DNA such as quantity, chromosomal alterations, sequence mutations and epigenetic changes, and can be used to guide and improve treatment throughout the course of the disease. This tremendous potential for real-time ‘tracking’ in a cancer patient has led to substantial research efforts in the ctDNA field. ctDNA can be distinguished from non-tumor DNA by the presence of tumor-specific mutations and copy number variations, and also by aberrant DNA methylation, with both DNA sequence and methylation changes corresponding to those found in the tumor. Aberrant methylation of specific promoter regions can be a very consistent feature of cancer, in contrast to mutations, which typically occur at a wide range of sites. This consistency makes ctDNA methylation amenable to the design of widely applicable clinical assays. In this review, we examine ctDNA methylation in the context of monitoring disease status, treatment response and determining the prognosis of cancer patients. PMID:26764421

  5. Cord blood-circulating endothelial progenitors for treatment of vascular diseases.

    PubMed

    Lavergne, M; Vanneaux, V; Delmau, C; Gluckman, E; Rodde-Astier, I; Larghero, J; Uzan, G

    2011-04-01

    Adult peripheral blood (PB) endothelial progenitor cells (EPC) are produced in the bone marrow and are able to integrate vascular structures in sites of neoangiogenesis. EPCs thus represent a potential therapeutic tool for ischaemic diseases. However, use of autologous EPCs in cell therapy is limited by their rarity in adult PB. Cord blood (CB) contains more EPCs than PB, and they are functional after expansion. They form primary colonies that give rise to secondary colonies, each yielding more than 10(7) cells after few passages. The number of endothelial cells obtained from one unit of CB is compatible with potential clinical application. EPC colonies can be securely produced, expanded and cryopreserved in close culture devices and endothelial cells produced in these conditions are functional as shown in different in vitro and in vivo assays. As CB EPC-derived endothelial cells would be allogeneic to patients, it would be of interest to prepare them from ready-existing CB banks. We show that not all frozen CB units from a CB bank are able to generate EPC colonies in culture, and when they do so, number of colonies is lower than that obtained with fresh CB units. However, endothelial cells derived from frozen CB have the same phenotypical and functional properties than those derived from fresh CB. This indicates that CB cryopreservation should be improved to preserve integrity of stem cells other than haematopoietic ones. Feasibility of using CB for clinical applications will be validated in porcine models of ischaemia.

  6. Elderly bioheat modeling: changes in physiology, thermoregulation, and blood flow circulation

    NASA Astrophysics Data System (ADS)

    Rida, Mohamad; Ghaddar, Nesreen; Ghali, Kamel; Hoballah, Jamal

    2014-01-01

    A bioheat model for the elderly was developed focusing on blood flow circulatory changes that influence their thermal response in warm and cold environments to predict skin and core temperatures for different segments of the body especially the fingers. The young adult model of Karaki et al. (Int J Therm Sci 67:41-51, 2013) was modified by incorporation of the physiological thermoregulatory and vasomotor changes based on literature observations of physiological changes in the elderly compared to young adults such as lower metabolism and vasoconstriction diminished ability, skin blood flow and its minimum and maximum values, the sweating values, skin fat thickness, as well as the change in threshold parameter related to core or skin temperatures which triggers thermoregulatory action for sweating, maximum dilatation, and maximum constriction. The developed model was validated with published experimental data for elderly exposure to transient and steady hot and cold environments. Predicted finger skin temperature, mean skin temperature, and core temperature were in agreement with published experimental data at a maximum error less than 0.5 °C in the mean skin temperature. The elderly bioheat model showed an increase in finger skin temperature and a decrease in core temperature in cold exposure while it showed a decrease in finger skin temperature and an increase in core temperature in hot exposure.

  7. [Changes in gingival blood circulation in patients with provisional fixed acrylic dentures].

    PubMed

    Shcherbakov, A S; Rudakova, Iu A; Ivanova, S B; Nekrasov, A N

    2015-01-01

    The adhesion of oral microorganisms to the surface of teeth and dental restorative materials is often the starting point in the developments of caries and periodontal disease. Formation of biofilm on the surface provisional acrylic bridge is especially quickly and can potentially generate decay or periodontal disease on the teeth. Occlusion trauma and occlusion disorders effects on increasing of injure regional periodontal tissues. Using ultrasonic doppler diagnostics oral mucosal blood flow was measured in 79 patients with periodontitis of medium severity with different hygiene conditions before and during orthopedic treatment by provisional fixed dentures was model by different methods. According to the results of this study was stated optimization of oral mucosal blood flow after pre-prosthetic treatments and the supportive hygiene periodontal care during the treatment. Results was used for reduce of functional stress in the in periodontal tissues during the orthopedic alignment by the use of fixed dentures. Specific prosthodontic hygiene protocol and model by individual articulator must be used to treat patients with widespread chronic periodontitis by interim prostheses. PMID:25909614

  8. Elderly bioheat modeling: changes in physiology, thermoregulation, and blood flow circulation.

    PubMed

    Rida, Mohamad; Ghaddar, Nesreen; Ghali, Kamel; Hoballah, Jamal

    2014-11-01

    A bioheat model for the elderly was developed focusing on blood flow circulatory changes that influence their thermal response in warm and cold environments to predict skin and core temperatures for different segments of the body especially the fingers. The young adult model of Karaki et al. (Int J Therm Sci 67:41-51, 2013) was modified by incorporation of the physiological thermoregulatory and vasomotor changes based on literature observations of physiological changes in the elderly compared to young adults such as lower metabolism and vasoconstriction diminished ability, skin blood flow and its minimum and maximum values, the sweating values, skin fat thickness, as well as the change in threshold parameter related to core or skin temperatures which triggers thermoregulatory action for sweating, maximum dilatation, and maximum constriction. The developed model was validated with published experimental data for elderly exposure to transient and steady hot and cold environments. Predicted finger skin temperature, mean skin temperature, and core temperature were in agreement with published experimental data at a maximum error less than 0.5 °C in the mean skin temperature. The elderly bioheat model showed an increase in finger skin temperature and a decrease in core temperature in cold exposure while it showed a decrease in finger skin temperature and an increase in core temperature in hot exposure.

  9. Detection by ELISA of circulating anti-blood fluke (Carettacola, Hapalotrema, and Learedius) immunoglobulins in Hawaiian green turtles (Chelonia mydas).

    PubMed

    Graczyk, T K; Aguirre, A A; Balazs, G H

    1995-06-01

    An enzyme-linked immunosorbent assay (ELISA) is described utilizing the surface glycocalyx crude antigen of adult blood trematodes Learedius learedi, Hapalotrema dorsopora, and Carettacola hawaiiensis, for the detection of circulating antibodies (Ab) in Hawaiian green turtles (Chelonia mydas) naturally infected with the parasites and with or without green turtle fibropapillomatosis (GTFP). A concentration of 10.0 micrograms/ml of antigen was optimal in terms of test specificity and sensitivity. A direct ELISA with anti-reptilian/amphibian phosphatase-labeled IgG identified C. mydas Ab at a dilution of 1/12,800. Utilizing indirect ELISA, it was possible to detect Ab to blood flukes at a dilution of 1/3,200. The gross lesions and histopathology were typical for cardiovascular spirorchidiasis in C. mydas. No significant relationship was found between the size of turtles and the degree of GTFP severity. Forty-seven of 59 (80%) samples, from 5 sites, gave a positive ELISA reaction; 6 of the 47 (13%) specimens gave significantly (P < 0.001) higher absorbance values, with 5 from the same location. All 12 (20%) ELISA-negative turtles originated from 1 site, and the absorbance values of the 41 animals from this location were significantly lower (P < 0.015) when compared with the other 4 sites. The proposed assay is fast, has the feature of visual scoring, and can be used for determination of exposure of C. mydas to the spirorchid trematodes.

  10. Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples.

    PubMed

    Gogoi, Priya; Sepehri, Saedeh; Zhou, Yi; Gorin, Michael A; Paolillo, Carmela; Capoluongo, Ettore; Gleason, Kyle; Payne, Austin; Boniface, Brian; Cristofanilli, Massimo; Morgan, Todd M; Fortina, Paolo; Pienta, Kenneth J; Handique, Kalyan; Wang, Yixin

    2016-01-01

    Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.

  11. Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples

    PubMed Central

    Gogoi, Priya; Sepehri, Saedeh; Zhou, Yi; Gorin, Michael A.; Paolillo, Carmela; Capoluongo, Ettore; Gleason, Kyle; Payne, Austin; Boniface, Brian; Cristofanilli, Massimo; Morgan, Todd M.; Fortina, Paolo; Pienta, Kenneth J.; Handique, Kalyan; Wang, Yixin

    2016-01-01

    Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization. PMID:26808060

  12. Acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo.

    PubMed

    Kubo, Keitaro; Ikebukuro, Toshihiro

    2012-10-01

    This study aimed to investigate the acute and chronic effects of hyperbaric oxygen therapy on blood circulation of human muscle and tendon in vivo. Using near-infrared spectroscopy and red laser lights, we determined acute changes in blood volume (THb) and oxygen saturation (StO2) of the medial gastrocnemius muscle and Achilles tendon during 60 minutes of hyperbaric oxygen therapy (1.3 atm absolute and 50% O2, experiment 1). In addition, we determined the chronic effects of hyperbaric oxygen therapy (60 minutes, 2 times per week, 6 weeks) on THb and StO2 of muscle and tendon (experiment 2). In experiment 1, THb of the muscle increased gradually from resting level, but StO2 did not change. On the other hand, THb and StO2 of the tendon increased during hyperbaric oxygen therapy. In experiment 2, the pattern of changes in the measured variables during 60 minutes of therapy was similar for both the muscle and tendon between the first and last therapies. During resting, THb and StO2 of the tendon were significantly lower after 6 weeks of therapy, although those of the muscle were not. In conclusion, oxygen saturation of the tendon increased during hyperbaric oxygen therapy, whereas that of the muscle did not. This result would be related to the difference in the treated effects between muscle and tendon. However, oxygen saturation of the tendon, but not the muscle, during resting decreased after 6 weeks of therapy.

  13. Effects of 5-HT1B/1D receptor agonist rizatriptan on cerebral blood flow and blood volume in normal circulation.

    PubMed

    Okazawa, Hidehiko; Tsuchida, Tatsuro; Pagani, Marco; Mori, Tetsuya; Kobayashi, Masato; Tanaka, Fumiko; Yonekura, Yoshiharu

    2006-01-01

    To investigate the vasoconstrictor effect of 5-hydroxytryptamine (5-HT1B/1D) receptor agonists for migraine treatment, changes in cerebral blood flow (CBF) and blood volume induced by rizatriptan were assessed by positron emission tomography (PET). Eleven healthy volunteers underwent PET studies before and after rizatriptan administration. Dynamic PET data were acquired after bolus injection of H2(15)O to analyze CBF and arterial-to-capillary blood volume (V0) images using the three-weighted integral method. After a baseline scan, three further acquisitions were performed at 40 to 50, 60 and 70 to 80 mins after drug administration. Global and regional differences in CBF and V0 between conditions were compared using absolute values in the whole brain and cortical regions, as well as statistical parametric mapping (SPM) analysis. The global and regional values for CBF and V0 decreased significantly after rizatriptan administration compared with the baseline condition. However, both values recovered to baseline within 80 mins after treatment. The maximal reduction in global CBF and V0 was approximately 13% of baseline value. The greatest decrease in CBF was observed approximately 60 mins after drug administration, whereas the maximal reduction in V0 was observed approximately 5 mins earlier. Statistical parametric mapping did not highlight any regional differences between conditions. Thus, in brain circulation, rizatriptan caused significant CBF and V0 decreases, which are consistent with the vasoconstrictor effect of triptans on the large cerebral arteries. The gradual recovery in the late phase from the maximal CBF and V0 decrease suggests that rizatriptan does not affect the cerebral autoregulatory response in small arteries induced by CBF reduction. PMID:15944648

  14. A model of the circulating blood for use in radiation dose calculations

    SciTech Connect

    Hui, T.E.; Poston, J.W. Sr.

    1987-12-31

    Over the last few years there has been a significant increase in the use of radionuclides in leukocyte, platelet, and erythrocyte imaging procedures. Radiopharmaceutical used in these procedures are confined primarily to the blood, have short half-lives, and irradiate the body as they move through the circulatory system. There is a need for a model, to describe the circulatory system in an adult human, which can be used to provide radiation absorbed dose estimates for these procedures. A simplified model has been designed assuming a static circulatory system and including major organs of the body. The model has been incorporated into the MIRD phantom and calculations have been completed for a number of exposure situations and radionuclides of clinical importance. The model will be discussed in detail and results of calculations using this model will be presented.

  15. A model of the circulating blood for use in radiation dose calculations

    SciTech Connect

    Hui, T.E.; Poston, J.W. Sr.

    1987-01-01

    Over the last few years there has been a significant increase in the use of radionuclides in leukocyte, platelet, and erythrocyte imaging procedures. Radiopharmaceutical used in these procedures are confined primarily to the blood, have short half-lives, and irradiate the body as they move through the circulatory system. There is a need for a model, to describe the circulatory system in an adult human, which can be used to provide radiation absorbed dose estimates for these procedures. A simplified model has been designed assuming a static circulatory system and including major organs of the body. The model has been incorporated into the MIRD phantom and calculations have been completed for a number of exposure situations and radionuclides of clinical importance. The model will be discussed in detail and results of calculations using this model will be presented.

  16. Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise.

    PubMed

    Churchward-Venne, Tyler A; Cotie, Lisa M; MacDonald, Maureen J; Mitchell, Cameron J; Prior, Todd; Baker, Steven K; Phillips, Stuart M

    2014-07-01

    Aging is associated with anabolic resistance, a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signaling through mTORC1. Twenty-one elderly males (65-80 yr) completed acute unilateral resistance exercise prior to being assigned to ingest a high dose (45 g) of whey protein (WHEY) or a low dose (15 g) of whey protein with 10 g of citrulline (WHEY + CIT) or with 10 g of nonessential amino acids (WHEY + NEAA). A primed, continuous infusion of L-[ring-(13)C6] phenylalanine with serial muscle biopsies was used to measure MPS and protein phosphorylation, whereas ultrasound was used to measure microvascular circulation under basal and postprandial conditions in both a rested (FED) and exercised (EX-FED) leg. Argininemia was greater in WHEY + CIT vs. WHEY and WHEY + NEAA from 30 to 300 min postexercise (P < 0.001), but there were no treatment differences in blood flow or microvascular perfusion (all P > 0.05). Phosphorylation of p70S6K-Thr(389) was greater in WHEY vs. WHEY + NEAA (P = 0.02). Postprandial MPS was greater in WHEY vs. WHEY + CIT and WHEY + NEAA under both FED (WHEY: ~128%; WHEY + CIT: ~56%; WHEY + NEAA: ~38%) and EX-FED (WHEY: ~251%; WHEY + CIT: ~124%; WHEY + NEAA: ~108%) conditions (P = 0.003). Citrulline coingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared with nonessential amino acids.

  17. Circulating immune complexes of calves with bronchopneumonia modulate the function of peripheral blood leukocytes: In vitro evaluation.

    PubMed

    Buač, Marijana; Mojsilović, Slavko; Mišić, Dušan; Vuković, Dejan; Savić, Olivera; Valčić, Olivera; Marković, Dragana; Gvozdić, Dragan; Ilić, Vesna; Fratrić, Natalija

    2016-06-01

    In this work we studied if circulating immune complexes (CIC) of calves with bronchopneumonia have the capacity to modulate function of peripheral blood leukocytes of healthy cattle. CIC of three month old calves (6 healthy and 6 diseased) were isolated by PEG precipitation. Peripheral blood mononuclear cells (MNCs) and granulocytes from healthy calves and cows were the CIC responder cells in in vitro tests. The most remarkable increase of adhesiveness to polystyrene and ROS synthesis (assessed by NBT test) was detected in cows' granulocytes stimulated with CIC of diseased calves. Results of MTT test showed that CIC of both healthy and diseased calves reduced granulocytes' viability. The strongest effect of inhibition of cows' granulocytes resulted from CIC of diseased calves. CIC only moderately reduced spontaneous viability of calves' MNCs. Again, the strongest effect of CIC isolated from diseased calves was observed. In contrast to the low impact of CIC on non-stimulated cells, their inhibitory effect on viability of mitogen stimulated MNCs was very strong. With CFSE assay we showed that both types of CIC stimulated spontaneous, but inhibited mitogen induced proliferation of calves' MNCs. Propidium iodide staining reviled that CIC increased apoptosis/necrosis of both non-stimulated and mitogen stimulated MNCs. CIC of both healthy and diseased calves modulated the function of peripheral blood MNCs and granulocytes, but a stronger effect of CIC of diseased calves was shown. The age of the donors (calves or cows) of the responder cells, and the activation state of these cells, were also of influence. PMID:27234551

  18. Peanut agglutinin appearance in the blood circulation after peanut ingestion mimics the action of endogenous galectin-3 to promote metastasis by interaction with cancer-associated MUC1.

    PubMed

    Zhao, Qicheng; Duckworth, Carrie A; Wang, Weikun; Guo, Xiuli; Barrow, Hannah; Pritchard, D Mark; Rhodes, Jonathan M; Yu, Lu-Gang

    2014-12-01

    Peanut agglutinin (PNA), which accounts for ~0.15% of the weight of the common peanut, is a carbohydrate-binding protein that binds the oncofoetal Thomsen-Friedenreich (TF) disaccharide (galactoseβ1,3N-acetylgalactosamineα-) that is overexpressed by ~90% of human cancers. Previous studies have shown that PNA is highly resistant to cooking and digestion and rapidly enters the human blood circulation after peanut ingestion. This study investigates the hypothesis that PNA appearance in the circulation after peanut ingestion may mimic the actions of endogenous TF-binding human galectin-3 in metastasis promotion. It shows that PNA at concentrations similar to those found in blood circulation after peanut ingestion increases cancer cell heterotypic adhesion to the blood vascular endothelium and enhances the formation of tumour cell homotypic aggregates, two important steps in the metastasis cascade, and enhances metastasis in a mouse metastasis model. These effects of PNA are shown to result from its interaction with the cancer-associated TF disaccharide on the transmembrane mucin protein MUC1, causing MUC1 cell surface polarization that reveals underlying cell surface adhesion molecules. Thus, PNA appearance in the blood circulation after peanut ingestion mimics the actions of endogenous galectin-3 and promotes cancer cell metastatic spread by interaction with cancer-associated TF/MUC1. As metastasis accounts for the majority of cancer-associated fatality, regular consumption of peanuts by cancer patients would therefore be expected to have an adverse effect on cancer survival.

  19. Environmental exposure to metals and male reproductive hormones: Circulating testosterone is inversely associated with blood molybdenum

    PubMed Central

    Meeker, John D.; Rossano, Mary G.; Protas, Bridget; Padmanabhan, Vasantha; Diamond, Michael P.; Puscheck, Elizabeth; Daly, Douglas; Paneth, Nigel; Wirth, Julia J.

    2010-01-01

    Study Objective To explore associations between exposure to metals and male reproductive hormone levels. Design Cross-sectional epidemiology study with adjustment for potential confounders. Setting Metal concentrations and reproductive hormone levels were measured in blood samples collected from 219 men. Patients: Men recruited through two Michigan, USA infertility clinics. Interventions None Main Outcome Measures Serum FSH, LH, inhibin B, testosterone, and SHBG. Results Cadmium, copper and lead were all significantly or suggestively positively associated with testosterone when modeled individually (p-values = 0.1, 0.03, and 0.07, respectively), findings that are consistent with limited previous human and animal studies. Conversely, molybdenum was associated with reduced testosterone (p-value for trend = 0.001). A significant inverse trend between molybdenum and testosterone remained when additionally considering other metals in the model, where a positive association between testosterone and zinc was also found. Finally, in exploratory analysis there was evidence for an interaction between molybdenum and zinc, where high molybdenum was associated with a 37% reduction in testosterone (relative to the population median level) among men with low zinc. Conclusions While reductions in testosterone and reproductive toxicity following molybdenum exposure have been previously demonstrated in animal studies, more research is needed to determine whether molybdenum poses a risk to human reproductive health. PMID:18990371

  20. [The autonomic nervous system and blood circulation system during different modes of anesthetic coinduction].

    PubMed

    Mikaelian, K P; Zaĭtsev, A Iu; Svetlov, V A; Golovkin, A S

    2009-01-01

    The autonomic nervous system (ANS) at the stage of induction was studied in 128 spinal surgical patients with chronic pain syndrome (CPS) (ASA 2-3). In all groups premedication was similar (diazepam 10 mg i.m.), intramuscular and intravenous atropine 0.5 was additionally injected in Groups 3 and 4, respectively. Introductory anesthesia used 4 coinduction modes: thiopental, fentanyl, and propofol (Group 1); propofol and fentanyl (Group 2); propofol, medazolam, and fentanyl (Groups 3 and 4). BIS monitoring was used to evaluate the impact of anesthesia and sedation on the central nervous system; autonomic screening and the Kerdo index were employed for the ANS. Intraoperative circulatory function was controlled by the values of blood pressure, heart rate, stroke index, cardiac index (CI), total peripheral resistance, and double product. Assessment of the time course of changes in ANS tone in patients with CPS indicated that after premedication, the number of parasympathotonics ranged up to 82% and that of normo- and sympathotonics was reduced to 13 and 5%, respectively. During induction with vagotonic agents, ignoring the baseline ANS tone was followed by a progression of the parasympathetic reaction of the circulatory system as a drop of CI to the low values of relevant dissadjustment in the hypokinetic hemodynamic type. There was a transition of ANS tone to physiological sympathicotonia and, accordingly, to the eukinetic circulatory type during coinduction mode 4 that suppressed vagus reflex.

  1. In Vivo Biomolecule Corona around Blood-Circulating, Clinically Used and Antibody-Targeted Lipid Bilayer Nanoscale Vesicles.

    PubMed

    Hadjidemetriou, Marilena; Al-Ahmady, Zahraa; Mazza, Mariarosa; Collins, Richard F; Dawson, Kenneth; Kostarelos, Kostas

    2015-08-25

    The adsorption of proteins and their layering onto nanoparticle surfaces has been called the "protein corona". This dynamic process of protein adsorption has been extensively studied following in vitro incubation of many different nanoparticles with plasma proteins. However, the formation of protein corona under dynamic, in vivo conditions remains largely unexplored. Extrapolation of in vitro formed protein coronas to predict the fate and possible toxicological burden from nanoparticles in vivo is of great interest. However, complete lack of such direct comparisons for clinically used nanoparticles makes the study of in vitro and in vivo formed protein coronas of great importance. Our aim was to study the in vivo protein corona formed onto intravenously injected, clinically used liposomes, based on the composition of the PEGylated liposomal formulation that constitutes the anticancer agent Doxil. The formation of in vivo protein corona was determined after the recovery of the liposomes from the blood circulation of CD-1 mice 10 min postinjection. In comparison, in vitro protein corona was formed by the incubation of liposomes in CD-1 mouse plasma. In vivo and in vitro formed protein coronas were compared in terms of morphology, composition and cellular internalization. The protein coronas on bare (non-PEGylated) and monoclonal antibody (IgG) targeted liposomes of the same lipid composition were also comparatively investigated. A network of linear fibrillary structures constituted the in vitro formed protein corona, whereas the in vivo corona had a different morphology but did not appear to coat the liposome surface entirely. Even though the total amount of protein attached on circulating liposomes correlated with that observed from in vitro incubations, the variety of molecular species in the in vivo corona were considerably wider. Both in vitro and in vivo formed protein coronas were found to significantly reduce receptor binding and cellular internalization of

  2. In Vivo Biomolecule Corona around Blood-Circulating, Clinically Used and Antibody-Targeted Lipid Bilayer Nanoscale Vesicles.

    PubMed

    Hadjidemetriou, Marilena; Al-Ahmady, Zahraa; Mazza, Mariarosa; Collins, Richard F; Dawson, Kenneth; Kostarelos, Kostas

    2015-08-25

    The adsorption of proteins and their layering onto nanoparticle surfaces has been called the "protein corona". This dynamic process of protein adsorption has been extensively studied following in vitro incubation of many different nanoparticles with plasma proteins. However, the formation of protein corona under dynamic, in vivo conditions remains largely unexplored. Extrapolation of in vitro formed protein coronas to predict the fate and possible toxicological burden from nanoparticles in vivo is of great interest. However, complete lack of such direct comparisons for clinically used nanoparticles makes the study of in vitro and in vivo formed protein coronas of great importance. Our aim was to study the in vivo protein corona formed onto intravenously injected, clinically used liposomes, based on the composition of the PEGylated liposomal formulation that constitutes the anticancer agent Doxil. The formation of in vivo protein corona was determined after the recovery of the liposomes from the blood circulation of CD-1 mice 10 min postinjection. In comparison, in vitro protein corona was formed by the incubation of liposomes in CD-1 mouse plasma. In vivo and in vitro formed protein coronas were compared in terms of morphology, composition and cellular internalization. The protein coronas on bare (non-PEGylated) and monoclonal antibody (IgG) targeted liposomes of the same lipid composition were also comparatively investigated. A network of linear fibrillary structures constituted the in vitro formed protein corona, whereas the in vivo corona had a different morphology but did not appear to coat the liposome surface entirely. Even though the total amount of protein attached on circulating liposomes correlated with that observed from in vitro incubations, the variety of molecular species in the in vivo corona were considerably wider. Both in vitro and in vivo formed protein coronas were found to significantly reduce receptor binding and cellular internalization of

  3. Significant Biochemical, Biophysical and Metabolic Diversity in Circulating Human Cord Blood Reticulocytes

    PubMed Central

    Malleret, Benoît; Xu, Fenggao; Mohandas, Narla; Suwanarusk, Rossarin; Chu, Cindy; Leite, Juliana A.; Low, Kayen; Turner, Claudia; Sriprawat, Kanlaya; Zhang, Rou; Bertrand, Olivier; Colin, Yves; Costa, Fabio T. M.; Ong, Choon Nam; Ng, Mah Lee; Lim, Chwee Teck; Nosten, Francois; Rénia, Laurent; Russell, Bruce

    2013-01-01

    Background The transition from enucleated reticulocytes to mature normocytes is marked by substantial remodeling of the erythrocytic cytoplasm and membrane. Despite conspicuous changes, most studies describe the maturing reticulocyte as a homogenous erythropoietic cell type. While reticulocyte staging based on fluorescent RNA stains such as thiazole orange have been useful in a clinical setting; these ‘sub-vital’ stains may confound delicate studies on reticulocyte biology and may preclude their use in heamoparasite invasion studies. Design and Methods Here we use highly purified populations of reticulocytes isolated from cord blood, sorted by flow cytometry into four sequential subpopulations based on transferrin receptor (CD71) expression: CD71high, CD71medium, CD71low and CD71negative. Each of these subgroups was phenotyped in terms of their, morphology, membrane antigens, biomechanical properties and metabolomic profile. Results Superficially CD71high and CD71medium reticulocytes share a similar gross morphology (large and multilobular) when compared to the smaller, smooth and increasingly concave reticulocytes as seen in the in the CD71low and CD71negativesamples. However, between each of the four sample sets we observe significant decreases in shear modulus, cytoadhesive capacity, erythroid receptor expression (CD44, CD55, CD147, CD235R, and CD242) and metabolite concentrations. Interestingly increasing amounts of boric acid was found in the mature reticulocytes. Conclusions Reticulocyte maturation is a dynamic and continuous process, confounding efforts to rigidly classify them. Certainly this study does not offer an alternative classification strategy; instead we used a nondestructive sampling method to examine key phenotypic changes of in reticulocytes. Our study emphasizes a need to focus greater attention on reticulocyte biology. PMID:24116088

  4. [Study of the systemic-organ blood circulation in acute period of the multiple trauma based on water-electrolytic metabolism and its correction with EHF-therapy].

    PubMed

    Malykhin, A V

    2005-01-01

    In the present paper the new approach to study of relationships of system blood circulation and its correction with the help of effect of EHF-therapy on the organism of person is offered. The method is based on the study of dynamic indexes of water-electrolytic metabolism, cell structure of a blood, ECG, REG, computer-aided tomography of the brain. The correlation between cell structure of blood, ionic structure and dynamic indexes of water-electrolytic metabolism is found out. Some parameters, factor of solubility of oxygen, parameters of a common water of organism were designed.

  5. [IMPACT OF QUERCETIN ON SYSTEMIC AND SPLANCHNIC BLOOD CIRCULATION IN A COMPLEX OF PREOPERATIVE PREPARATION IN PATIENTS, SUFFERING AN ACUTE PANCREATITIS].

    PubMed

    Datsyuk, O I

    2016-01-01

    The results of prospective investigation of 76 patients, suffering an acute pancreatitis, in whom Quercetin was applied in content of a starting liquid resuscitation in complex of preoperative preparation, were studied. Its impact on the indices of systemic and splanchnic blood circulation, as well as results of an acute pancreatitis treatment was studied. Inclusion of Quercetin into a scheme of the patients preoperative preparation have promoted the improvement of indices of systemic hemodynamics and the cardiac pump function and enhancement of the left ventricle mechanical work by 18.4% (p < 0.01) at average. A trustworthy reduction of the peak systolic velocity of blood flow in the splanchnic space vessels was established. The systemic and regional blood circulation improvement caused a reduction of the organ dysfunction rate, as well as polyorgan insufficiency from 71.4 to 28.6%.

  6. Single skin exposure to visible polarized light induces rapid modification of entire circulating blood: II. Appearance of soluble factors restoring proliferation and chromosome structure in X-damag

    NASA Astrophysics Data System (ADS)

    Samoilova, Kira A.; Zubanova, O. I.; Snopov, S. A.; Mukhuradze, N. A.; Mikhelson, V. M.

    1998-12-01

    Exposure of a small skin area (400 cm2) of volunteers to visible incoherent polarized (VIP) light (400 - 2000 nm) in therapeutic doses is accompanied by rapid appearance in the circulating blood of soluble factors able to restore proliferation of X-ray-damaged autologous lymphocytes and to decrease frequency of chromosome breaks. The appearance of a such activity in blood can also be induced without skin irradiation, by in vitro modeling of mixing in the circulation of a small amount of transcutaneously VIP- irradiated blood with the intact blood (one volume of the directly VIP-irradiated blood was added to 10 volumes of the intact blood). Hence, the blood (not the skin) is a major source of the active factors. The data obtained indicate a possibility of release of them from photomodified platelets; moreover, the activity restoring chromosome structure in X- damaged cells has been found in the platelet-derived growth factor and epidermal growth factor (which are known to be associated with platelets) when they were added to physiological concentrations to the culture medium. We assume that activation of cell proliferation based on the effective repair of DNA damaged in situ by endogenous and exogenous factors could be one of the mechanisms of photostimulation of wound healing.

  7. Influence of urea on the glucose measurement by electrocatalytic sensor in the extracorporeal blood circulation of a sheep.

    PubMed

    Saeger, S; Preidel, W; von Lucadou, I; Ruprecht, L; Lager, W

    1991-01-01

    In an animal experiment with the electrocatalytic glucose sensor, measurements were carried out over one week in the extracorporeal circulation of a sheep. Glucose tolerance tests were performed, and the influence of increased urea concentrations in the blood on the glucose determination was investigated. The sensor constructed as a flow-through cell was integrated via a vascular graft outside the body into the carotid artery of the animal and activated by an external electronic unit of measurement. The glucose concentration was determined by measuring the impedance of the electrode/membrane system at various potentials. By means of a subsequent correlation analysis of the measured values obtained over one week, a calibration valid for the entire measurement period was established. After a zero adjustment, it was even possible to adopt the calibration from the glucose measurement of the preceding animal experiment. The investigations of the influence of urea on the glucose measurement showed that the error in measurement of the sensor, which is 20% on average, is only insignificantly increased when the urea level is raised beyond the maximum physiological concentration. PMID:1759967

  8. Mechanisms of adaptation of the hepatic vasculature to the deteriorating conditions of blood circulation in liver cirrhosis

    PubMed Central

    Garbuzenko, Dmitry Victorovich; Arefyev, Nikolay Olegovich; Belov, Dmitry Vladimirovich

    2016-01-01

    PubMed, EMBASE, Orphanet, MIDLINE, Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015. Relevant articles were selected by using the following terms: “Liver cirrhosis”, “Endothelial dysfunction”, “Sinusoidal remodeling”, “Intrahepatic angiogenesis” and “Pathogenesis of portal hypertension”. Then the reference lists of identified articles were searched for other relevant publications as well. Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules, the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis. It is characterized by endothelial dysfunction and impaired paracrine interaction between activated stellate hepatocytes and sinusoidal endotheliocytes, sinusoidal remodeling and capillarization, as well as development of the collateral microcirculation. In spite of the fact that complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis in liver cirrhosis are the compensatory-adaptive reaction to the deteriorating conditions of blood circulation, they contribute to progression of disease and development of serious complications, in particular, related to portal hypertension. PMID:27326313

  9. A biomimetic microfluidic chip to study the circulation and mechanical retention of red blood cells in the spleen.

    PubMed

    Picot, Julien; Ndour, Papa Alioune; Lefevre, Sophie D; El Nemer, Wassim; Tawfik, Harvey; Galimand, Julie; Da Costa, Lydie; Ribeil, Jean-Antoine; de Montalembert, Mariane; Brousse, Valentine; Le Pioufle, Bruno; Buffet, Pierre; Le Van Kim, Caroline; Français, Olivier

    2015-04-01

    Red blood cells (RBCs) are deformable and flow through vessels narrower than their own size. Their deformability is most stringently challenged when they cross micrometer-wide slits in the spleen. In several inherited or acquired RBC disorders, blockade of small vessels by stiff RBCs can trigger organ damage, but a functional spleen is expected to clear these abnormal RBCs from the circulation before they induce such complications. We analyzed flow behavior of RBCs in a microfluidic chip that replicates the mechanical constraints imposed on RBCs as they cross the human spleen. Polymer microchannels obtained by soft lithography with a hydraulic diameter of 25 μm drove flow into mechanical filtering units where RBCs flew either slowly through 5- to 2-μm-wide slits or rapidly along 10-μm-wide channels, these parallel paths mimicking the splenic microcirculation. Stiff heated RBCs accumulated in narrow slits seven times more frequently than normal RBCs infused simultaneously. Stage-dependent retention of Plasmodium falciparum-infected RBCs was also observed in these slits. We also analyzed RBCs from patients with hereditary spherocytosis and observed retention for those having the most altered mechanical properties as determined by ektacytometry. Thus, in keeping with previous observations in vivo and ex vivo, the chip successfully discriminated poorly deformable RBCs based on their distinct mechanical properties and on the intensity of the cell alteration. Applications to the exploration of the pathogenesis of malaria, hereditary spherocytosis, sickle cell disease and other RBC disorders are envisioned. PMID:25641515

  10. A biomimetic microfluidic chip to study the circulation and mechanical retention of red blood cells in the spleen.

    PubMed

    Picot, Julien; Ndour, Papa Alioune; Lefevre, Sophie D; El Nemer, Wassim; Tawfik, Harvey; Galimand, Julie; Da Costa, Lydie; Ribeil, Jean-Antoine; de Montalembert, Mariane; Brousse, Valentine; Le Pioufle, Bruno; Buffet, Pierre; Le Van Kim, Caroline; Français, Olivier

    2015-04-01

    Red blood cells (RBCs) are deformable and flow through vessels narrower than their own size. Their deformability is most stringently challenged when they cross micrometer-wide slits in the spleen. In several inherited or acquired RBC disorders, blockade of small vessels by stiff RBCs can trigger organ damage, but a functional spleen is expected to clear these abnormal RBCs from the circulation before they induce such complications. We analyzed flow behavior of RBCs in a microfluidic chip that replicates the mechanical constraints imposed on RBCs as they cross the human spleen. Polymer microchannels obtained by soft lithography with a hydraulic diameter of 25 μm drove flow into mechanical filtering units where RBCs flew either slowly through 5- to 2-μm-wide slits or rapidly along 10-μm-wide channels, these parallel paths mimicking the splenic microcirculation. Stiff heated RBCs accumulated in narrow slits seven times more frequently than normal RBCs infused simultaneously. Stage-dependent retention of Plasmodium falciparum-infected RBCs was also observed in these slits. We also analyzed RBCs from patients with hereditary spherocytosis and observed retention for those having the most altered mechanical properties as determined by ektacytometry. Thus, in keeping with previous observations in vivo and ex vivo, the chip successfully discriminated poorly deformable RBCs based on their distinct mechanical properties and on the intensity of the cell alteration. Applications to the exploration of the pathogenesis of malaria, hereditary spherocytosis, sickle cell disease and other RBC disorders are envisioned.

  11. Hypothesis: the systemic circulation as a regulated free-market economy. A new approach for understanding the long-term control of blood pressure.

    PubMed

    Fink, Gregory D

    2005-01-01

    1. The purpose of the present paper is to discuss the long-term regulation of arterial blood pressure. Current thinking on the topic favours the theory that tight regulation is achieved through the action of a central (or primary) controller, usually assumed to be in either the brain or kidneys. 2. Here, an alternative explanation is considered; namely, that the average long-term level of arterial pressure is an emergent property of a decentralized control system. The goal of the system is to deliver nutrient-rich blood to distinct vascular regions based on their energy demand. 3. Specifically, the circulation is conceptualized as a free-market economy where tissues 'compete' for a scarce resource (the energy contained in blood) supplied by the heart-lung unit; the 'price' of the resource (analogous to the reciprocal of arterial pressure) is determined primarily by the dynamic relationship between supply and demand, not by a central mechanism. 4. Based on this concept of the circulation as an energy market, economic analogies are used to suggest novel mechanisms by which the brain and kidney may affect the long-term control of blood pressure. 5. Market-based control, a process derived from quantitative theoretical analysis of the performance of economic markets, is proposed as a new, potentially useful strategy for mathematically modelling the behaviour of the circulation.

  12. Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans.

    PubMed

    Sergeant, Susan; Ruczinski, Ingo; Ivester, Priscilla; Lee, Tammy C; Morgan, Timothy M; Nicklas, Barbara J; Mathias, Rasika A; Chilton, Floyd H

    2016-01-28

    Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk.

  13. Effects of a chicken collagen hydrolysate on the circulation system in subjects with mild hypertension or high-normal blood pressure.

    PubMed

    Kouguchi, Tomomi; Ohmori, Takashi; Shimizu, Muneshige; Takahata, Yoshihisa; Maeyama, Yoshiaki; Suzuki, Takuya; Morimatsu, Fumiki; Tanabe, Soichi

    2013-01-01

    We investigated the effects of a chicken collagen hydrolysate (CCH) on the circulation system in humans. A total of 58 subjects with either mild hypertension (systolic blood pressure (SBP) of 140-159 mmHg or diastolic blood pressure (DBP) 90-99 mmHg) or high-normal blood pressure (SBP 130-139 mmHg or DBP 85-89 mmHg) were assigned to two groups, one involving a placebo and the other, the test food (including CCH of 2.9 g/d). The parameters related to each subject's circulation system were monitored over the study period of 18 weeks. The Δbrachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness and marker of vascular damage, was significantly lower in the test food group than in the placebo group during the treatment period. The blood pressure in the test food group was also significantly lower than that in the placebo group, while the serum nitrogen oxide was higher in the test food group after the treatment. These results suggest that CCH exerted modulatory effects on the human circulation system.

  14. A Subpopulation of Circulating Endothelial Cells Express CD109 and is Enriched in the Blood of Cancer Patients

    PubMed Central

    Mancuso, Patrizia; Calleri, Angelica; Gregato, Giuliana; Labanca, Valentina; Quarna, Jessica; Antoniotti, Pierluigi; Cuppini, Lucia; Finocchiaro, Gaetano; Eoli, Marica; Rosti, Vittorio; Bertolini, Francesco

    2014-01-01

    Background The endothelium is not a homogeneous organ. Endothelial cell heterogeneity has been described at the level of cell morphology, function, gene expression, and antigen composition. As a consequence of the genetic, transcriptome and surrounding environment diversity, endothelial cells from different vascular beds have differentiated functions and phenotype. Detection of circulating endothelial cells (CECs) by flow cytometry is an approach widely used in cancer patients, and their number, viability and kinetic is a promising tool to stratify patient receiving anti-angiogenic treatment. Methodology/Principal Findings Currently CECs are identified as positive for a nuclear binding antigen (DNA+), negative for the pan leukocyte marker CD45, and positive for CD31 and CD146. Following an approach recently validated in our laboratory, we investigated the expression of CD109 on CECs from the peripheral blood of healthy subject and cancer patients. The endothelial nature of these cells was validated by RT-PCR for the presence of m-RNA level of CDH5 (Ve-Cadherin) and CLDN5 (Claudin5), two endothelial specific transcripts. Before treatment, significantly higher levels of CD109+ CECs and viable CD109+CECs were found in breast cancer patients and glioblastoma patients compared to healthy controls, and their number significantly decreased after treatment. Higher levels of endothelial specific transcripts expressed in developing endothelial cells CLEC14a, TMEM204, ARHGEF15, GPR116, were observed in sorted CD109+CECs when compared to sorted CD146+CECs, suggesting that these genes can play an important role not only during embryogenesis but also in adult angiogenesis. Interestingly, mRNA levels of TEM8 (identified as Antrax Toxin Receptor1, Antrax1) were expressed in CD109+CECs+ but not in CD146+CECs. Conclusion Taken together our results suggest that CD109 represent a rare population of circulating tumor endothelial cells, that play a potentially useful prognostic role in

  15. The granzyme B inhibitor SERPINB9 (protease inhibitor 9) circulates in blood and increases on primary cytomegalovirus infection after renal transplantation.

    PubMed

    Rowshani, Ajda T; Strik, Merel C M; Molenaar, Rosalie; Yong, Si-La; Wolbink, Angela M; Bemelman, Frederike J; Hack, C Erik; Ten Berge, Ineke J M

    2005-12-01

    SERPINB9 is the only known human intracellular inhibitor of granzyme B (GrB), the effector molecule in immunity against cytomegalovirus (CMV) and in renal allograft rejection. Therefore, using specific enzyme-linked immunosorbent assays, we addressed the presence of circulating SERPINB9 during primary CMV infection, subclinical rejection, acute rejection, and uncomplicated posttransplantation course. Soluble (s) SERPINB9 circulates in blood and increases on primary CMV infection. This increase was significantly higher in symptomatic than in asymptomatic patients. In contrast, sSERPINB9 levels did not change in response to subclinical or acute rejection. We demonstrated the presence of circulating sSERPINB9/sGrB complexes, which suggests that SERPINB9 has extracellular functions as well.

  16. Accelerated removal of antibody-coated red blood cells from the circulation is accurately tracked by a biotin label

    PubMed Central

    Mock, Donald M.; Lankford, Gary L.; Matthews, Nell I.; Burmeister, Leon F.; Kahn, Daniel; Widness, John A.; Strauss, Ronald G.

    2013-01-01

    BACKGROUND Safe, accurate methods to reliably measure circulating red blood cell (RBC) kinetics are critical tools to investigate pathophysiology and therapy of anemia, including hemolytic anemias. This study documents the ability of a method using biotin-labeled RBCs (BioRBCs) to measure RBC survival (RCS) shortened by coating with a highly purified monomeric immunoglobulin G antibody to D antigen. STUDY DESIGN AND METHODS Autologous RBCs from 10 healthy D+ subjects were labeled with either biotin or 51Cr (reference method), coated (opsonized) either lightly (n = 4) or heavily (n = 6) with anti-D, and transfused. RCS was determined for BioRBCs and for 51Cr independently as assessed by three variables: 1) posttransfusion recovery at 24 hours (PTR24) for short-term RCS; 2) time to 50% decrease of the label (T50), and 3) mean potential life span (MPL) for long-term RCS. RESULTS BioRBCs tracked both normal and shortened RCS accurately relative to 51Cr. For lightly coated RBCs, mean PTR24, T50, and MPL results were not different between BioRBCs and 51Cr. For heavily coated RBCs, both short-term and long-term RCS were shortened by approximately 17 and 50%, respectively. Mean PTR24 by BioRBCs (84 ± 18%) was not different from 51Cr (81 ± 10%); mean T50 by BioRBCs (23 ± 17 days) was not different from 51Cr (22 ± 18 days). CONCLUSION RCS shortened by coating with anti-D can be accurately measured by BioRBCs. We speculate that BioRBCs will be useful for studying RCS in conditions involving accelerated removal of RBCs including allo- and autoimmune hemolytic anemias. PMID:22023312

  17. Relationship between circulating tumor cells, blood coagulation, and urokinase-plasminogen-activator system in early breast cancer patients.

    PubMed

    Mego, Michal; Karaba, Marian; Minarik, Gabriel; Benca, Juraj; Sedlácková, Tatiana; Tothova, Lubomira; Vlkova, Barbora; Cierna, Zuzana; Janega, Pavol; Luha, Jan; Gronesova, Paulina; Pindak, Daniel; Fridrichova, Ivana; Celec, Peter; Reuben, James M; Cristofanilli, Massimo; Mardiak, Jozef

    2015-01-01

    Cancer is a risk factor for venous thromboembolism (VTE) and plasma d-dimer (DD) and tissue factor (TF) are established VTE associated markers. Circulating tumor cells (CTCs) are associated with the risk of VTE in metastatic breast cancer. This study aimed to correlate CTCs, blood coagulation and the urokinase plasminogen activator (uPA) system in primary breast cancer (PBC) patients. This prospective study included 116 PBC patients treated by primary surgery. CTCs were detected by quantitative RT-PCR assay for expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1, FOXC2). Plasma DD, TF, uPA system proteins were detected by enzyme-linked immunosorbent assays, while expressions of uPA system in surgical specimens were evaluated by immunohistochemistry. CTCs were detected in 27.6% patients. Patients with CTCs had a significantly higher mean plasma DD (ng/mL) than those of patients without CTCs (632.4 versus 365.4, p = 0.000004). There was no association between plasma TF and CTCs. Epithelial CTCs exhibit higher expression of uPA system genes compared to EMT_CTCs. Patients with CTCs had higher plasma uPA proteins than those of patients without CTCs; there was no correlation between tissue expression of uPA system, CTCs, DD or TF levels. In multivariate analysis CTCs and patients age were independent factors associated with plasma DD. We found association between plasma DD and CTCs indicating a potential role for activation of the coagulation cascade in the early metastatic process. CTCs could be directly involved in coagulation activation or increased CTCs could be marker of aggressive disease and increased VTE risk.

  18. A novel cabazitaxel-loaded polymeric micelle system with superior in vitro stability and long blood circulation time.

    PubMed

    Han, Xiaoxiong; Chen, Dan; Sun, Jing; Zhou, Jinsong; Li, Duan; Gong, Feirong; Shen, Yaling

    2016-01-01

    Cabazitaxel (CTX) is a second-generation semisynthetic taxane that demonstrates antitumor activity superior to docetaxel. However, the low aqueous solubility of CTX has hampered its use as a therapeutic agent. In this work, CTX-loaded N-t-butoxycarbonyl-L-phenylalanine end-capped monomethyl poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PLA-Phe(Boc)/CTX) micelles were prepared to improve the solubility of CTX while retaining its superior stability before accessing the tumor site. The mPEG-PLA-Phe(Boc)/CTX micelles showed excellent stability in vitro compared with mPEG-PLA/CTX micelles. When stored at 25 °C, the mPEG-PLA/CTX micelles tended to aggregate within 1 h, whereas the mPEG-PLA-Phe(Boc)/CTX micelles were uniformly transparent even after three weeks. Dilution of mPEG-PLA/CTX micelles widened their size distribution and decreased the encapsulation efficiency, while significant change was not found in mPEG-PLA-Phe(Boc)/CTX micelles, even when diluted 1000-fold. Pharmacokinetic results in Sprague-Dawley rats indicated that, compared with Jevtana(®), intravenous administration of mPEG-PLA-Phe(Boc)/CTX micelles stably retained the CTX in plasma with 26.03-fold larger of the area under the time-concentration curve, 2.13-fold longer of the half-life, and 9.99-fold higher of the maximum concentration. In conclusion, mPEG-PLA-Phe(Boc) micelle may be a potential nanocarrier not only to improve the solubility of CTX but also to prolong the blood circulation time, which results in improved biological activity.

  19. In situ quantitative monitoring of polyplexes and polyplex micelles in the blood circulation using intravital real-time confocal laser scanning microscopy.

    PubMed

    Nomoto, Takahiro; Matsumoto, Yu; Miyata, Kanjiro; Oba, Makoto; Fukushima, Shigeto; Nishiyama, Nobuhiro; Yamasoba, Tatsuya; Kataoka, Kazunori

    2011-04-30

    Surface modification using poly(ethylene glycol) (PEG) is a widely used strategy to improve the biocompatibility of cationic polymer-based nonviral gene vectors (polyplexes). A novel method based on intravital real-time confocal laser scanning microscopy (IVRTCLSM) was applied to quantify the dynamic states of polyplexes in the bloodstream, thereby demonstrating the efficacy of PEGylation to prevent their agglomeration. Blood flow in the earlobe blood vessels of experimental animals was monitored in a noninvasive manner to directly observe polyplexes in the circulation. Polyplexes formed distinct aggregates immediately after intravenous injection, followed by interaction with platelets. To quantify aggregate formation and platelet interaction, the coefficient of variation and Pearson's correlation coefficient were adopted. In contrast, polyplex micelles prepared through self-assembly of plasmid DNA with PEG-based block catiomers had dense PEG palisades, revealing no formation of aggregates without visible interaction with platelets during circulation. This is the first report of in situ monitoring and quantification of the availability of PEGylation to prevent polyplexes from agglomeration over time in the blood circulation. This shows the high utility of IVRTCLSM in drug and gene delivery research.

  20. Blood

    MedlinePlus

    ... solid part of your blood contains red blood cells, white blood cells, and platelets. Red blood cells (RBC) deliver oxygen from your lungs to your tissues and organs. White blood cells (WBC) fight infection and are part of your ...

  1. Optical Microangiography: A Label Free 3D Imaging Technology to Visualize and Quantify Blood Circulations within Tissue Beds in vivo

    PubMed Central

    Wang, Ruikang K

    2009-01-01

    Optical microangiography (OMAG) is a recently developed volumetric imaging technique that is capable of producing 3D images of dynamic blood perfusion within microcirculatory tissue beds in vivo. The imaging contrast of OMAG image is based on the intrinsic optical scattering signals backscattered by the moving blood cells in patent blood vessels, thus it is a label free imaging technique. In this paper, I will first discuss its recent developments that use a constant modulation frequency introduced in the spectral interferograms to achieve the blood perfusion imaging. I will then introduce its latest development that utilizes the inherent blood flow to modulate the spectral interferograms to realize the blood perfusion imaging. Finally, examples of using OMAG to delineate the dynamic blood perfusion, down to capillary level resolution, within living tissues are given, including cortical blood perfusion in the brain of small animals and blood flow within human retina and choroids. PMID:20657761

  2. Optical Microangiography: A Label Free 3D Imaging Technology to Visualize and Quantify Blood Circulations within Tissue Beds in vivo.

    PubMed

    Wang, Ruikang K

    2010-05-01

    Optical microangiography (OMAG) is a recently developed volumetric imaging technique that is capable of producing 3D images of dynamic blood perfusion within microcirculatory tissue beds in vivo. The imaging contrast of OMAG image is based on the intrinsic optical scattering signals backscattered by the moving blood cells in patent blood vessels, thus it is a label free imaging technique. In this paper, I will first discuss its recent developments that use a constant modulation frequency introduced in the spectral interferograms to achieve the blood perfusion imaging. I will then introduce its latest development that utilizes the inherent blood flow to modulate the spectral interferograms to realize the blood perfusion imaging. Finally, examples of using OMAG to delineate the dynamic blood perfusion, down to capillary level resolution, within living tissues are given, including cortical blood perfusion in the brain of small animals and blood flow within human retina and choroids.

  3. Detection of Circulating Tumor DNA in Human Blood via DNA-Mediated Surface-Enhanced Raman Spectroscopy of Single-Walled Carbon Nanotubes.

    PubMed

    Zhou, Qifeng; Zheng, Jing; Qing, Zhihe; Zheng, Mengjie; Yang, Jinfeng; Yang, Sheng; Ying, Le; Yang, Ronghua

    2016-05-01

    The levels of circulating tumor DNA (ctDNA) in the peripheral blood have been associated with tumor burden and malignant progression. However, ultrasensitive detection of ctDNA in blood remains to be explored. Herein, we have developed a new approach, employing DNA-mediated surface-enhanced Raman scattering (SERS) of single-walled carbon nanotubes (SWNTs), that allows ultrasensitive detection of a broad range of ctDNAs in human blood. Combined with the efficient ctDNA recognition capacity of our designed triple-helix molecular switch and RNase HII enzyme-assisted amplification, the T-rich DNA-mediated SERS enhancement of SWNTs could read out a content of KRAS G12DM as low as 0.3 fM, with a detection of 5.0 μL of sample volume, which has potential for point-of-care testing in clinical analysis. PMID:27028517

  4. Effects of adaptive support ventilation and synchronized intermittent mandatory ventilation on peripheral circulation and blood gas markers of COPD patients with respiratory failure.

    PubMed

    Han, Ling; Wang, Yingxiao; Gan, Yonghua; Xu, Lijun

    2014-09-01

    The objective of the study was to investigate the effects of adaptive support ventilation (ASV) and synchronized intermittent mandatory ventilation (SIMV) on peripheral circulation of chronic obstructive pulmonary disease (COPD) patients with respiratory failure. 86 COPD patients with respiratory failure were recruited in this study. Self-control method was used to compare the effect of ASV and SIMV on the parameters of ventilation machine, heart rate, blood pressure, central venous pressure (CVP), and blood gas markers. When the patients in ASV and SIMV groups were compared, respiratory rate, tidal volume, and peak airway pressure (PIP) showed significant difference. When minute ventilation (MV) was compared, no significant difference was shown. When peripheral circulation parameters were compared, peripheral circulation heart rate, SBP, DBP, and CVP showed significant difference. Compared with SIMV group, PaO2, pH, and SaO2 values were remarkably increased (P < 0.01) while no significant difference was found for partial pressure of carbon dioxide (pCO2) when two groups were compared. In conclusion, when mechanical ventilation was used in COPD patients with respiratory failure, ASV can significantly improve clinical outcomes.

  5. Successful one-lung ventilation in a patient with the Fontan circulation undergoing thoracoscopic procedure.

    PubMed

    Cvetkovic, Draginja; Ramzy, Wassim; Vitale, Salvatore; Malekan, Ramin; Warsy, Irfan

    2014-12-01

    Over the course of the past 4 decades, the survival of patients with the Fontan circulation has improved and today they often present for noncardiac surgery anesthesia care. In patients with the Fontan circulation, pulmonary blood flow is passive and anesthetic management is directed at reducing pulmonary vascular resistance and maintaining adequate cardiac output. One-lung ventilation can have unfavorable effects on the Fontan circulation due to hypoxia, hypercarbia, and increased airway pressure. We present a case of successful one-lung ventilation in a patient with the Fontan circulation and describe the perioperative anesthetic management.

  6. Haematopoiesis and a new mechanism for the release of mature blood cells from the bone marrow into the circulation in snakes (Ophidia).

    PubMed

    Sano-Martins, I Sigueko; Dabrowski, Z; Tabarowski, Z; Witkowska-Pelc, E; Spadacci Morena, D Denelle; Spodaryk, K

    2002-10-01

    This is the first description of haematopoiesis in snakes. Studies were carried out on the following species belonging to Ophidia: Bothrops jararaca, Bothrops jararacusu, Waglerophis merremii, Elaphe taeniura taeniura, Boa constrictor,and Python reticulatus. Smears of the peripheral blood and histological preparations from the vertebrae, ribs, liver, and spleen were studied under a light and electron microscope. Myeloid cells were present in the following locations in the vertebrae: the neural spine, zygoapophysial processes, floor of the neural canal, lacunae in the bodies of vertebrae and also inside the ribs. Although the vascular system was well developed, especially around the ribs, vessels inside the marrow cavities were scarce, both in the ribs and elsewhere where haematopoiesis was found. Venous sinuses were well developed in the vertebrae and in the rib regions from their costal head towards the middle area. They consisted of one layer of fine endothelial cells. Mature cells in the process of migration into the general circulation were only sporadically encountered when venous sinuses were studied on perfusion-fixed specimens. In contrast, almost every sinus venosus contained protrusions directed towards the lumen, filled mostly with mature and immature blood cells. Various stages of their formation were seen in the cross sections of venous sinuses ranging from small, newly formed to large, elongated ones, filled with many fully developed and some maturing blood cells. In many cases the apices of the protrusions were ruptured, and mature blood cells, as well as a few immature ones, were seen in their vicinity. This observation led us to a new hypothesis that blood cells are released from the extravascular space into the lumen of venous sinuses. In snakes, these cells are released into the systemic circulation mainly via the rupture of protrusions filled with mature blood cells and, to a lesser degree, by transcytosis as known in mammals. In the spleens

  7. [Absence of HTLV-I/II virus circulation in blood donors from the provinces of Santa Fe and Santiago del Estero].

    PubMed

    Gastaldello, R; Fazzola, P; Caeiro, L; Maturano, E; Perez De Rosas, A; Fernandez, I; Racca, R; Rodriguez, M B; Molina, M; Alonso, S; Gallego, S

    2002-01-01

    In the present study, we evaluated the seroprevalence of HTLV-I/II infection among the blood donors in Santa Fe and Santiago del Estero provinces. A total of 1327 serum samples from blood donors from Rafaela blood bank of Santa Fe province and 3382 serum samples from blood donors from Dr Edgar Bouzon blood bank of Santiago del Estero province were studied. The antibody screening was done by particle agglutination assay (PA) (SERODIA, Fujirebio Inc., Tokyo, Japan) or by enzyme immuno assay (EIA) (Abbott HTLV-I/HTLV-II EIA, Abbott, Germany). The "in house" indirect immunofluorescence assay (IFA) and Western blot (Bioblot HTLV Biokit, Barcelona, Spain) were used as confirmatory assays. All the samples resulted negative for specific antibodies against HTLV-I/II. These results suggest that HTLV-I/II are not circulating in low risk populations in these provinces or that the prevalences of infection would be lower than that reported by blood banks in other provinces of Argentina.

  8. [The role of nitric oxide in regulation of the erythrocyte system state in rat offspring with chronic disturbance of uteroplacental blood circulation].

    PubMed

    Nazarov, S B; Ivanova, A S; Novikov, A A

    2012-01-01

    The effect of exogenous nitric oxide donor deponit-10 (nitroglycerin) on red cell indices in the offspring of rats with experimental disturbances of uteroplacental circulation has been investigated. It is established that fetal hypoxia facilitates the mobilization of functional reserves of the red cell system in the prenatal and early days of postnatal life of offspring in white rats, which is manifested by the growing process of erythropoiesis. Hyperfunction of the erythrocyte system in the first lifedays of pups leads eventually to a depletion of its functional capacities. The administration of an exogenous nitric oxide donor on the background of damaged uteroplacental circulation prevents the depletion and disruption of the functional reserves of the blood red cell system.

  9. Stealth CD44-targeted hyaluronic acid supramolecular nanoassemblies for doxorubicin delivery: probing the effect of uncovalent pegylation degree on cellular uptake and blood long circulation.

    PubMed

    Han, Xiaopeng; Li, Zhenbao; Sun, Jin; Luo, Cong; Li, Lin; Liu, Yuhai; Du, Yuqian; Qiu, Shuhong; Ai, Xiaoyu; Wu, Chunnuan; Lian, He; He, Zhonggui

    2015-01-10

    Stealth active targeting nanoparticles (NPs) usually include two types of ligand sites: ligand anchored on distal ends of the polyethylene glycol (PEG) and ligand buried under pegylated layer. The latter typical case is hyaluronic acid (HA)-based NPs; however, there is little information available for the latter NPs about effect of the optimal density of surface PEG coating on the blood circulation time, cellular uptake and in vivo anticancer activity. Thus, in this study, in order to optimize the anticancer effects of HA-based NPs, we focus on how uncovalent pegylation degree modulates blood circulation time and cellular uptake of HA-based NPs. We firstly designed a new double-hydrophilic copolymer by conjugating HP-β-cyclodextrin with HA, and this carrier was further pegylated with adamantyl-peg (ADA-PEG) to form inclusion complex HA-HPCD/ADA-PEG, termed as HCPs. The supramolecular nanoassemblies were fabricated by host-guest and polar interactions between HCPs and doxorubicin (Dox), with vitamin E succinate (VES) being a nanobridge. Despite the active recognition between HA and CD44 receptor, the cellular uptake and targeting efficiency of HA-NPs decreased with the increasing peg density, demonstrating HA was partly buried by high density peg coating. However, the high density of peg coating was beneficial to long circulation time, tumor biodistribution and anticancer activity in vivo. NPs with 5% peg coating had the optimal cellular targeting efficiency in vitro and anticancer effects in vivo. The findings suggest that balancing long circulation property and cellular uptake is important to achieve the optimal antitumor efficacy for pegylated HA-based NPs, and that PEG coating densities cannot be extended beyond a certain density for shielding effect without compromising the efficacy of hyaluronic acid targeted delivery.

  10. Micropallet arrays for the capture, isolation and culture of circulating tumor cells from whole blood of mice engrafted with primary human pancreatic adenocarcinoma.

    PubMed

    Gach, Philip C; Attayek, Peter J; Whittlesey, Rebecca L; Yeh, Jen Jen; Allbritton, Nancy L

    2014-04-15

    Circulating tumor cells (CTCs) are important biomarkers of cancer progression and metastatic potential. The rarity of CTCs in peripheral blood has driven the development of technologies to isolate these tumor cells with high specificity; however, there are limited techniques available for isolating target CTCs following enumeration. A strategy is described to capture and isolate viable tumor cells from whole blood using an array of releasable microstructures termed micropallets. Specific capture of nucleated cells or cells expressing epithelial cell adhesion molecules (EpCAM) was achieved by functionalizing micropallet surfaces with either fibronectin, Matrigel or anti-EpCAM antibody. Surface grafting of poly(acrylic acid) followed by covalent binding of protein A/G enabled efficient capture of EpCAM antibody on the micropallet surface. MCF-7 cells, a human breast adenocarcinoma, were retained on the array surface with 90±8% efficiency when using an anti-EpCAM-coated array. To demonstrate the efficiency of tumor cell retention on micropallet arrays in the presence of blood, MCF-7 cells were mixed into whole blood and added to small arrays (71 mm(2)) coated with fibronectin, Matrigel or anti-EpCAM. These approaches achieved MCF-7 cell capture from ≤10 µL of whole blood with efficiencies greater than 85%. Furthermore, MCF-7 cells intermixed with 1 mL blood and loaded onto large arrays (7171 mm(2)) were captured with high efficiencies (≥97%), could be isolated from the array by a laser-based approach and were demonstrated to yield a high rate of colony formation (≥85%) after removal from the array. Clinical utility of this technology was shown through the capture, isolation and successful culture of CTCs from the blood of mice engrafted with primary human pancreatic tumors. Direct capture and isolation of living tumor cells from blood followed by analysis or culture will be a valuable tool for cancer cell characterization.

  11. Anticoagulation management associated with extracorporeal circulation.

    PubMed

    Sniecinski, Roman M; Levy, Jerrold H

    2015-06-01

    The use of extracorporeal circulation requires anticoagulation to maintain blood fluidity throughout the circuit, and to prevent thrombotic complications. Additionally, adequate suppression of hemostatic activation avoids the unnecessary consumption of coagulation factors caused by the contact of blood with foreign surfaces. Cardiopulmonary bypass represents the greatest challenge in this regard, necessitating profound levels of anticoagulation during its conduct, but also quick, efficient reversal of this state once the surgical procedure is completed. Although extracorporeal circulation has been around for more than half a century, many questions remain regarding how to best achieve anticoagulation for it. Although unfractionated heparin is the predominant agent used for cardiopulmonary bypass, the amount required and how best to monitor its effects are still unresolved. This review discusses the use of heparin, novel anticoagulants, and the monitoring of anticoagulation during the conduct of cardiopulmonary bypass.

  12. Biochemical assessment of growth factors and circulation of blood components contained in the different fractions obtained by centrifugation of venous blood.

    PubMed

    Corigiano, M; Ciobanu, G; Baldoni, E; Pompa, G

    2014-01-01

    The aim of this study was to evaluate a biochemical marker with different elements of a normal blood serum and centrifuged blood serum after a different rotation system. For this technique, we used five fractions of a blood Concentrated Growth Factors system (bCGF) and a particular device for the different rotation program. Blood samples were collected from 10 volunteers aged between 35 and 55 in the Operative Unit of the “Sapienza” University of Rome with only a fraction of different biochemical elements. Through an individual blood phase separator tube of venous blood, active factions of serum and 4 fractions of red buffy coat were taken. The biochemical markers with 14 elements were examined at times: P1-11 minutes, P2-12minutes, P3-15 minutes. Exclusively biological materials which are normally applied in the regeneration techniques for different defects and lesions were used with this technique. After specific rotation programs, a different result was obtained for each cycle: P1, P2, P3. In test tubes obtained by separated blood, we observed a higher concentration of proteins, ions, and other antigens compared to normal blood plasma. Examining the biochemical results of different elements, we observed an increase (P≤0,01). Since each person’s DNA is different, we could not have the same results in 5 fractions of blood concentration, we did, however, find a good increase in only a fraction of proteins, immunoglobulin and different ions. We obtained five fractions after centrifugation, and we had an increase in different biochemical elements compared to normal blood (P≤0,01) which is significant at different times. These biochemical elements were stimulated by different growth factors, which are used by the immune system, and they induced the formation of hard and soft tissues and good regeneration.

  13. Active tissue factor and activated factor XI in circulating blood of patients with systolic heart failure due to ischemic cardiomyopathy

    PubMed Central

    Zabczyk, Michał; Butenas, Saulius; Palka, Ilona; Nessler, Jadwiga; Undas, Anetta

    2011-01-01

    INTRODUCTION Elevated clotting factors and thrombin generation have been reported to occur in patients with heart failure (HF). Circulating activated factor XI (FXIa) and active tissue factor (TF) can be detected in acute coronary syndromes and stable angina. OBJECTIVES We investigated circulating FXIa and active TF and their associations in patients with systolic HF due to ischemic cardiomyopathy. PATIENTS AND METHODS In an observational study, we assessed 53 consecutive patients, aged below 75 years, with stable HF associated with documented coronary artery disease (CAD). Atrial fibrillation (LA), recent thromboembolic events, and current anticoagulant therapy were the exclusion criteria. Plasma TF and FXIa activity was determined in clotting assays by measuring the response to inhibitory monoclonal antibodies. RESULTS Coagulant TF activity was detected in 20 patients (37.7%), and FXIa in 22 patients (41.5%). Patients with detectable TF activity and/or FXIa were younger, had a history of myocardial infarction more frequently, significantly higher F1+2 prothrombin fragments, larger LA and right ventricular diastolic diameter, and higher right ventricular systolic pressure than the remaining subjects (P ≤0.01 for all). Circulating FXIa was positively correlated with F1+2 levels (r = 0.69; P <0.001). CONCLUSIONS Circulating active TF and FXIa occurred in about 40% of patients with systolic HF due to ischemic cardiomyopathy. The presence of these factors was associated with enhanced thrombin formation. Associations between both factors and LA diameter and right ventricular parameters might suggest that TF and FXIa predispose to thromboembolic complications of HF. PMID:20864906

  14. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.

    PubMed

    Biancardi, Vinicia Campana; Son, Sook Jin; Ahmadi, Sahra; Filosa, Jessica A; Stern, Javier E

    2014-03-01

    Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood-brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.

  15. Glycosyltransferases as marker genes for the quantitative polymerase chain reaction-based detection of circulating tumour cells from blood samples of patients with breast cancer undergoing adjuvant therapy.

    PubMed

    Kölbl, Alexandra C; Hiller, Roman A; Ilmer, Mathias; Liesche, Friederike; Heublein, Sabine; Schröder, Lennard; Hutter, Stefan; Friese, Klaus; Jeschke, Udo; Andergassen, Ulrich

    2015-08-01

    Altered glycosylation is a predominant feature of tumour cells; it serves for cell adhesion and detachment, respectively, and facilitates the immune escape of these cells. Therefore changes in the expression of glycosyltransferase genes could help to identify circulating tumour cells (CTCs) in the blood samples of cancer patients using a quantitative polymerase chain reaction (PCR) approach. Blood samples of healthy donors were inoculated with certain numbers of established breast cancer cell line cells, thus creating a model system. These samples were analysed by quantitative PCR for the expression of six different glycosyltransferase genes. The three genes with the best results in the model system were consecutively applied to samples from adjuvant breast cancer patients and of healthy donors. FUT3 and GALNT6 showed the highest increase in relative expression, while GALNT6 and ST3GAL3 were the first to reach statistically significant different ∆CT-values comparing the sample with and without addition of tumour cells. These three genes were applied to patient samples, but did not show any significant results that may suggest the presence of CTCs in the blood. Although the relative expression of some of the glycosyltransferase genes exhibited reasonable results in the model system, their application to breast cancer patient samples will have to be further improved, e.g. by co-analysis of patient blood samples by gold-standard methods.

  16. [The status of splanchnic blood circulation in patients with varicose veins of the esophagus and stomach in liver cirrhosis].

    PubMed

    Kotenko, O G

    1999-01-01

    Complex hemodynamical investigations were done in 166 patients with liver cirrhosis and the portal hypertension syndrome. Patients with varicose veins of the esophagus and stomach versus patients with isolated varicose veins of the esophagus have significantly higher resistance of vessels of the a. hepatica and v. porta systems, more pronounced losses of portal perfusion at the expense of varicose veins of stomach, gastro- and splenorenal shunts and lower volumetric blood flow in v. lienalis. While varicose veins of the esophagus and stomach occur an absolute values of the arterial and portal blood flow in liver are lowering, common hepatic blood flow reduces. The varicose veins of the stomach existence testifies high degree of the portosystemic shunting development with subsequent lowering of volumetric blood flow in v. lienalis in comparison with such in isolated varicose veins of the esophagus.

  17. A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire

    PubMed Central

    SAUCEDO-ZENI, NADIA; MEWES, STEFFI; NIESTROJ, ROBERT; GASIOROWSKI, LUKASZ; MURAWA, DAVID; NOWACZYK, PIOTR; TOMASI, TATIANA; WEBER, EKKEHARD; DWORACKI, GRZEGORZ; MORGENTHALER, NILS G.; JANSEN, HEIKE; PROPPING, CORINNA; STERZYNSKA, KAROLINA; DYSZKIEWICZ, WOJCIECH; ZABEL, MACIEJ; KIECHLE, MARION; REUNING, UTE; SCHMITT, MANFRED; LÜCKE, KLAUS

    2012-01-01

    The isolation of circulating tumor cells (CTCs) from the blood of patients afflicted with solid malignant tumors becomes increasingly important as it may serve as a ‘liquid biopsy’ with the potential of monitoring the course of the cancer disease and its response to cancer therapy, with subsequent molecular characterization. For this purpose, we functionalized a structured medical Seldinger guidewire (FSMW), normally used to obtain safe access to blood vessels and other organ cavities, with a chimeric monoclonal antibody directed to the cell surface expressed epithelial cell surface adhesion molecule (EpCAM). This medical device was optimized in vitro and its biocompatibility was tested according to the regulations for medical devices and found to be safe with no noteworthy side effects. Suitability, specificity and sensitivity of the FSMW to catch and enrich CTCs in vivo from circulating peripheral blood were tested in 24 breast cancer or non-small cell lung cancer (NSCLC) patients and in 29 healthy volunteers. For this, the FSMW was inserted through a standard venous cannula into the cubital veins of healthy volunteers or cancer patients for the duration of 30 min. After removal, CTCs were identified by immunocytochemical staining of EpCAM and/or cytokeratins and staining of their nuclei and counted. The FSMW successfully enriched EpCAM-positive CTCs from 22 of the 24 patients, with a median of 5.5 (0–50) CTCs in breast cancer (n=12) and 16 (2–515) CTCs in NSCLC (n=12). CTCs could be isolated across all tumor stages, including early stage cancer, in which distant metastases were not yet diagnosed, while no CTCs could be detected in healthy volunteers. In this observatory study, no adverse effects were noted. Evidently, the FSMW has the potential to become an important device to enrich CTCs in vivo for monitoring the course of the cancer disease and the efficacy of anticancer treatment. PMID:22825490

  18. Balancing cationic and hydrophobic content of PEGylated siRNA polyplexes enhances endosome escape, stability, blood circulation time, and bioactivity in vivo.

    PubMed

    Nelson, Christopher E; Kintzing, James R; Hanna, Ann; Shannon, Joshua M; Gupta, Mukesh K; Duvall, Craig L

    2013-10-22

    A family of pH-responsive diblock polymers composed of poly[(ethylene glycol)-b-[(2-(dimethylamino)ethyl methacrylate)-co-(butyl methacrylate)], PEG-(DMAEMA-co-BMA), was reversible addition-fragmentation chain transfer (RAFT) synthesized with 0-75 mol % BMA in the second polymer block. The relative mole % of DMAEMA and BMA was varied in order to identify a polymer that can be used to formulate PEGylated, siRNA-loaded polyplex nanoparticles (NPs) with an optimized balance of cationic and hydrophobic content in the NP core based on siRNA packaging, cytocompatibility, blood circulation half-life, endosomal escape, and in vivo bioactivity. The polymer with 50:50 mol % of DMAEMA:BMA (polymer "50 B") in the RAFT-polymerized block efficiently condensed siRNA into 100 nm NPs that displayed pH-dependent membrane disruptive behavior finely tuned for endosomal escape. In vitro delivery of siRNA with polymer 50 B produced up to 94% protein-level knockdown of the model gene luciferase. The PEG corona of the NPs blocked nonspecific interactions with constituents of human whole blood, and the relative hydrophobicity of polymer 50 B increased NP stability in the presence of human serum or the polyanion heparin. When injected intravenously, 50 B NPs enhanced blood circulation half-life 3-fold relative to more standard PEG-DMAEMA (0 B) NPs (p < 0.05), due to improved stability and a reduced rate of renal clearance. The 50 B NPs enhanced siRNA biodistribution to the liver and other organs and significantly increased gene silencing in the liver, kidneys, and spleen relative to the benchmark polymer 0 B (p < 0.05). These collective findings validate the functional significance of tuning the balance of cationic and hydrophobic content of polyplex NPs utilized for systemic siRNA delivery in vivo.

  19. Blood circulation in the fingers is aggravated after creating a vascular access for dialysis: assessment using skin perfusion pressure.

    PubMed

    Sato, Makoto; Tahara, Shinya; Sugiyama, Daisuke; Terashi, Hiroto

    2014-10-01

    Internal vascular shunts for haemodialysis can cause different complications. One of the most serious complications is steal syndrome, which can result in disturbed peripheral circulation causing finger necrosis and lead to amputation. Thus, prevention of these complications is important. Measurement of skin perfusion pressure (SPP) has been used in various clinical settings, including wound-healing management, and its usefulness has been increasingly unveiled. The present study was undertaken to evaluate changes in haemodynamics after internal shunt creation by measuring SPP of the thumb and the little finger before and after surgery in five patients undergoing shunt surgery using the radial artery and the cephalic vein. The study revealed average changes of -22.8 mmHg in thumb SPP. The change in the thumb was statistically significant (p < 0.05). If the effect of surgery and the threshold for wound healing are taken into account, the present results indicate the necessity to pay extra attention to fingers with extremely low preoperative SPP values. For the prevention of serious disturbances of peripheral circulation (e.g. steal syndrome), routine preoperative SPP measurement seems effective for screening of high-risk patients.

  20. Hepatitis B virus and hepatitis D virus in blood donors from Argentina: circulation of HBsAg and reverse transcriptase mutants.

    PubMed

    Delfino, Cecilia María; Gentile, Emiliano Alberto; Castillo, Amalia Inés; Cuestas, María Luján; Pataccini, Gabriela; Cánepa, Camila; Malan, Richard; Blejer, Jorgelina; Berini, Carolina; Eirin, María Emilia; Pedrozo, Williams; Oubiña, José Raúl; Biglione, Mirna Marcela; Mathet, Verónica Lidia

    2014-05-01

    In Argentina, current procedures to ensure the safety of the blood supply for transfusion include the serologic detection of specific blood-borne infections. The aim of this study was to evaluate the prevalence and the genetic diversity of hepatitis B virus (HBV) and hepatitis D virus (HDV) in blood donor populations from two distantly located Argentine regions. Data from 56,983 blood donations from the Favaloro Foundation, in the city of Buenos Aires (Central Region), and the Central Blood Bank of Misiones Province (Northeast Region) were analyzed. Samples that were reactive for HBsAg were analyzed for HBV-DNA characterization and HDV serological and molecular analysis. The HBV prevalence was 0.12 % for HBsAg and 1.68 % for anti-HBc antibodies in Buenos Aires, and 0.73 % and 8.55 %, respectively, in Misiones. Seventy-seven HBsAg-reactive samples were analyzed by polymerase chain reaction for HBV-DNA. Subgenotypes A2, B2, C2, F1b and F4 (Buenos Aires) and F1b and D3 (Misiones) were detected. Several mutations within the major hydrophilic region of HBsAg, the reverse transcriptase, the basal core promoter, and the precore/core were detected. HDV genotype 1 was identified in Buenos Aires. This study confirms the circulation of several HBV subgenotypes, as well as known and newly identified variants, and the presence of HDV1 in this population. A thorough investigation has to be carried out to evaluate the clinical importance of some of the documented mutations as well as those detected in the HDV1 case.

  1. Hepatitis B virus and hepatitis D virus in blood donors from Argentina: circulation of HBsAg and reverse transcriptase mutants.

    PubMed

    Delfino, Cecilia María; Gentile, Emiliano Alberto; Castillo, Amalia Inés; Cuestas, María Luján; Pataccini, Gabriela; Cánepa, Camila; Malan, Richard; Blejer, Jorgelina; Berini, Carolina; Eirin, María Emilia; Pedrozo, Williams; Oubiña, José Raúl; Biglione, Mirna Marcela; Mathet, Verónica Lidia

    2014-05-01

    In Argentina, current procedures to ensure the safety of the blood supply for transfusion include the serologic detection of specific blood-borne infections. The aim of this study was to evaluate the prevalence and the genetic diversity of hepatitis B virus (HBV) and hepatitis D virus (HDV) in blood donor populations from two distantly located Argentine regions. Data from 56,983 blood donations from the Favaloro Foundation, in the city of Buenos Aires (Central Region), and the Central Blood Bank of Misiones Province (Northeast Region) were analyzed. Samples that were reactive for HBsAg were analyzed for HBV-DNA characterization and HDV serological and molecular analysis. The HBV prevalence was 0.12 % for HBsAg and 1.68 % for anti-HBc antibodies in Buenos Aires, and 0.73 % and 8.55 %, respectively, in Misiones. Seventy-seven HBsAg-reactive samples were analyzed by polymerase chain reaction for HBV-DNA. Subgenotypes A2, B2, C2, F1b and F4 (Buenos Aires) and F1b and D3 (Misiones) were detected. Several mutations within the major hydrophilic region of HBsAg, the reverse transcriptase, the basal core promoter, and the precore/core were detected. HDV genotype 1 was identified in Buenos Aires. This study confirms the circulation of several HBV subgenotypes, as well as known and newly identified variants, and the presence of HDV1 in this population. A thorough investigation has to be carried out to evaluate the clinical importance of some of the documented mutations as well as those detected in the HDV1 case. PMID:24306325

  2. Circulating serotonin in vertebrates.

    PubMed

    Maurer-Spurej, E

    2005-08-01

    The role of circulating serotonin is unclear and whether or not serotonin is present in the blood of non-mammalian species is not known. This study provides the first evidence for the presence of serotonin in thrombocytes of birds and three reptilian species, the endothermic leatherback sea turtle, the green sea turtle and the partially endothermic American alligator. Thrombocytes from a fresh water turtle, American bullfrog, Yellowfin tuna, and Chinook salmon did not contain serotonin. Serotonin is a vasoactive substance that regulates skin blood flow, a major mechanism for endothermic body temperature regulation, which could explain why circulating serotonin is present in warm-blooded species. The temperature sensitivity of human blood platelets with concomitant changes in serotonin content further supports a link between circulating serotonin and thermoregulation. Phylogenetic comparison of the presence of circulating serotonin indicated an evolutionary divergence within reptilian species that might coincide with the emergence of endothermy. PMID:16041566

  3. Measurement of Circulating Filarial Antigen Levels in Human Blood with a Point-of-Care Test Strip and a Portable Spectrodensitometer.

    PubMed

    Chesnais, Cédric B; Vlaminck, Johnny; Kunyu-Shako, Billy; Pion, Sébastien D; Awaca-Uvon, Naomi-Pitchouna; Weil, Gary J; Mumba, Dieudonné; Boussinesq, Michel

    2016-06-01

    The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detects Wuchereria bancrofti circulating filarial antigen (CFA) in human blood, serum, or plasma. The Global Program to Eliminate Lymphatic Filariasis employs the FTS for mapping filariasis-endemic areas and assessing the success of elimination efforts. The objective of this study was to explore the relationship between the intensity of positive test lines obtained by FTS with CFA levels as determined by enzyme-linked immunosorbent assay (ELISA) with blood and plasma samples from 188 individuals who live in a filariasis-endemic area. The intensity of the FTS test line was assessed visually to provide a semiquantitative score (visual Filariasis Test Strip [vFTS]), and line intensity was measured with a portable spectrodensitometer (quantitative Filariasis Test Strip [qFTS]). These results were compared with antigen levels measured by ELISA in plasma from the same subjects. qFTS measurements were highly correlated with vFTS scores (ρ = 0.94; P < 0.001) and with plasma CFA levels (ρ = 0.91; P < 0.001). Thus, qFTS assessment is a convenient method for quantifying W. bancrofti CFA levels in human blood, which are correlated with adult worm burdens. This tool may be useful for assessing the impact of treatment on adult filarial worms in individuals and communities. PMID:27114288

  4. Measurement of Circulating Filarial Antigen Levels in Human Blood with a Point-of-Care Test Strip and a Portable Spectrodensitometer

    PubMed Central

    Chesnais, Cédric B.; Vlaminck, Johnny; Kunyu-Shako, Billy; Pion, Sébastien D.; Awaca-Uvon, Naomi-Pitchouna; Weil, Gary J.; Mumba, Dieudonné; Boussinesq, Michel

    2016-01-01

    The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detects Wuchereria bancrofti circulating filarial antigen (CFA) in human blood, serum, or plasma. The Global Program to Eliminate Lymphatic Filariasis employs the FTS for mapping filariasis-endemic areas and assessing the success of elimination efforts. The objective of this study was to explore the relationship between the intensity of positive test lines obtained by FTS with CFA levels as determined by enzyme-linked immunosorbent assay (ELISA) with blood and plasma samples from 188 individuals who live in a filariasis-endemic area. The intensity of the FTS test line was assessed visually to provide a semiquantitative score (visual Filariasis Test Strip [vFTS]), and line intensity was measured with a portable spectrodensitometer (quantitative Filariasis Test Strip [qFTS]). These results were compared with antigen levels measured by ELISA in plasma from the same subjects. qFTS measurements were highly correlated with vFTS scores (ρ = 0.94; P < 0.001) and with plasma CFA levels (ρ = 0.91; P < 0.001). Thus, qFTS assessment is a convenient method for quantifying W. bancrofti CFA levels in human blood, which are correlated with adult worm burdens. This tool may be useful for assessing the impact of treatment on adult filarial worms in individuals and communities. PMID:27114288

  5. Circulating glioma biomarkers

    PubMed Central

    Kros, Johan M.; Mustafa, Dana M.; Dekker, Lennard J.M.; Sillevis Smitt, Peter A.E.; Luider, Theo M.; Zheng, Ping-Pin

    2015-01-01

    Validated biomarkers for patients suffering from gliomas are urgently needed for standardizing measurements of the effects of treatment in daily clinical practice and trials. Circulating body fluids offer easily accessible sources for such markers. This review highlights various categories of tumor-associated circulating biomarkers identified in blood and cerebrospinal fluid of glioma patients, including circulating tumor cells, exosomes, nucleic acids, proteins, and oncometabolites. The validation and potential clinical utility of these biomarkers is briefly discussed. Although many candidate circulating protein biomarkers were reported, none of these have reached the required validation to be introduced for clinical practice. Recent developments in tracing circulating tumor cells and their derivatives as exosomes and circulating nuclear acids may become more successful in providing useful biomarkers. It is to be expected that current technical developments will contribute to the finding and validation of circulating biomarkers. PMID:25253418

  6. Effect of PEG surface conformation on anticancer activity and blood circulation of nanoemulsions loaded with tocotrienol-rich fraction of palm oil.

    PubMed

    Alayoubi, Alaadin; Alqahtani, Saeed; Kaddoumi, Amal; Nazzal, Sami

    2013-10-01

    Tocotrienol-rich fraction of palm oil, which contains the isomers of vitamin E, was shown to possess potent anticancer activity against mammary adenocarcinoma cell lines. Its clinical use, however, is limited by poor oral bioavailability and short half-life. Previously, we developed tocotrienol-rich lipid nanoemulsions for intravenous administration. The objective of this study was to investigate the effect of surface grafted polyethylene glycol (PEG) on the properties of the nanoemulsions. PEGylation was achieved by the addition of equimolar PEG groups using poloxamer or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)2000] (PEG2000-DSPE). The effect of PEG surface topography on the antiproliferative activity of nanoemulsions against mammary adenocarcinoma cells, their susceptibility to protein adsorption, and its effect on blood hemolysis and circulation time was investigated. Nanoemulsions PEGylated with poloxamer or PEG2000-DSPE were stable under physical stress. Poloxamer nanoemulsion, however, displayed higher uptake and potency against MCF-7 tumor cells in 2D and 3D culture and increased hemolytic effect and susceptibility to IgG adsorption, which was reflected in its rapid clearance and short circulation half-life (1.7 h). Conversely, PEGylation with PEG2000-DSPE led to a 7-fold increase in mean residence time (12.3 h) after IV injection in rats. Reduced activity in vitro and improved circulation time suggested strong shielding of plasma proteins from the droplets. Differences between the nanoemulsions were attributed to polymer imbibitions and the differences in PEG conformation and density on the surface of the droplets.

  7. Action of alpha-galactosidase from Clostridium sporogenes and coffee beans on blood group B antigen of erythrocytes. The effect on the viability of erythrocytes in circulation.

    PubMed

    Dybus, S; Aminoff, D

    1983-01-01

    The effect of alpha-galactosidase, purified from Clostridium sporogenes (Maebashi), was examined on erythrocytes from rats, rabbits and gibbons. The amount of galactose released by alpha-galactosidase from Cl. sporogenes and from coffee beans was compared. The amount of sialic acid released by Vibrio cholera sialidase was also determined. Loss of blood group B specificity following treatment with alpha-galactosidase was demonstrated with anti-B lectin. In animal models, removal of all the alpha-galactosyl residues with the coffee bean or clostridial alpha-galactosidase resulted in no change in the sequestration pattern of the treated erythrocytes over a period of several days. In contrast, erythrocytes treated with sialidase were rapidly sequestered from the circulation.

  8. Rainbow trout (Oncorhynchus mykiss) shift the age composition of circulating red blood cells towards a younger cohort when exposed to thermal stress.

    PubMed

    Lewis, Johanne M; Klein, Georgia; Walsh, Patrick J; Currie, Suzanne

    2012-07-01

    Freshwater fish, such as the rainbow trout, are commonly exposed to temperature fluctuations in their aquatic environment. Exposure to increased temperatures places fish under respiratory stress and increases the likelihood of protein misfolding and degradation that could eventually lead to cell death. Previously, we showed that genes associated with the cellular stress response, apoptosis and hematopoiesis are upregulated in the red blood cells (RBCs) of rainbow trout post-thermal stress, leading to the hypothesis that a tightly regulated interaction between cell repair and cell death is occurring after heat stress. To test this hypothesis, we tracked changes in age class composition and markers of apoptosis in circulating RBCs within individual trout during exposure to and recovery from acute thermal stress. RBCs did not show any indication of apoptosis or necrosis following acute heat stress; however, we observed significant increases in numbers of early, juvenile and dividing RBCs. We also observed a shift in the composition of the circulating RBCs towards a younger cohort following heat shock through release of stored cells from the spleen and an increase in the maturation rate of early RBCs. These results suggest that the genes activated by increased temperature provided sufficient protection against thermal stress in the RBC, subsequently preventing the triggering of the cell death cascade.

  9. The expression and function of human CD300 receptors on blood circulating mononuclear cells are distinct in neonates and adults

    PubMed Central

    Zenarruzabeitia, Olatz; Vitallé, Joana; García-Obregón, Susana; Astigarraga, Itziar; Eguizabal, Cristina; Santos, Silvia; Simhadri, Venkateswara R.; Borrego, Francisco

    2016-01-01

    Neonates are more susceptible to infections than adults. This susceptibility is thought to reflect neonates’ qualitative and quantitative defects in the adaptive and innate immune responses. Differential expression of cell surface receptors may result in altered thresholds of neonatal immune cell activation. We determined whether the expression and function of the lipid-binding CD300 family of receptors are different on neonatal immune cells compared to adult immune cells. A multiparametric flow cytometry analysis was performed to determine the expression of CD300 receptors on adult peripheral blood mononuclear cells and neonatal cord blood mononuclear cells. The expression of the CD300a inhibitory receptor was significantly reduced on cells from the newborn adaptive immune system, and neonatal antigen presenting cells exhibited a different CD300 receptors expression pattern. We also found differential LPS-mediated regulation of CD300 receptors expression on adult monocytes compared to cord blood monocytes, and that CD300c and CD300e-mediated activation was quantitatively different in neonatal monocytes. This is the first complete study examining the expression of CD300 receptors on human neonatal immune cells compared with adult immune cells. Significant differences in the expression and function of CD300 receptors may help to explain the peculiarities and distinctness of the neonatal immune responses. PMID:27595670

  10. The expression and function of human CD300 receptors on blood circulating mononuclear cells are distinct in neonates and adults.

    PubMed

    Zenarruzabeitia, Olatz; Vitallé, Joana; García-Obregón, Susana; Astigarraga, Itziar; Eguizabal, Cristina; Santos, Silvia; Simhadri, Venkateswara R; Borrego, Francisco

    2016-01-01

    Neonates are more susceptible to infections than adults. This susceptibility is thought to reflect neonates' qualitative and quantitative defects in the adaptive and innate immune responses. Differential expression of cell surface receptors may result in altered thresholds of neonatal immune cell activation. We determined whether the expression and function of the lipid-binding CD300 family of receptors are different on neonatal immune cells compared to adult immune cells. A multiparametric flow cytometry analysis was performed to determine the expression of CD300 receptors on adult peripheral blood mononuclear cells and neonatal cord blood mononuclear cells. The expression of the CD300a inhibitory receptor was significantly reduced on cells from the newborn adaptive immune system, and neonatal antigen presenting cells exhibited a different CD300 receptors expression pattern. We also found differential LPS-mediated regulation of CD300 receptors expression on adult monocytes compared to cord blood monocytes, and that CD300c and CD300e-mediated activation was quantitatively different in neonatal monocytes. This is the first complete study examining the expression of CD300 receptors on human neonatal immune cells compared with adult immune cells. Significant differences in the expression and function of CD300 receptors may help to explain the peculiarities and distinctness of the neonatal immune responses. PMID:27595670

  11. Nourishing Yin and Promoting Blood Circulation of TCM to Treat Hemorheologic Disorder Induced by Diabetes Mellitus in Rats

    PubMed Central

    Huang, Ping; Shao, Guo-ming

    2007-01-01

    Diabetes mellitus, DM, is commonly accompanied with various stages of hemorheologic disturbances that are the main causes of the development of chronic DM. In this study, simple Chinese material medica [yang-yin jiang-tang preparation (YYJT)] was given to alloxan-induced DM rats and analyzed to compare the changes of fasting blood glucose (FBG), fasting insulin (FINS), hemorheologic parameters and insulin-like growth factor II (IGF-II) before and after administration. The results suggested that YYJT can significantly downregulate FBG (P < 0.005), improve insulin resistance and beta-cell secretion (P < 0.05), decrease whole blood viscosity at low and high shear rates, gathering of blood index test (GIT) and fibrinogen (FIB) (P < 0.05), and enlarge the function of IGF-II (P < 0.05). We concluded that YYJT could prevent and treat hemorheologic disorder in DM rats by means of reducing glucose, improving insulin resistance and elevating IGF-II. PMID:17549237

  12. Quantitative assessment of oscillatory components in blood circulation: classification of the effect of aging, diabetes, and acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Bernjak, Alan; Stefanovska, Aneta; Urbancic-Rovan, Vilma; Azman-Juvan, Katja

    2005-04-01

    The human cardiovascular system is a complex system with the pumping activity of the heart as the main generator of oscillations. Besides the heartbeat there are several other oscillatory components which determine its dynamics. Their nonlinear nature and a weak coupling between them both require special treatment while studying this system. A particular characteristic of the oscillatory components is their frequency fluctuations in time. Consequently, their interactions also fluctuate in time. Therefore the wavelet transform is applied to trace the oscillatory components in time, and specific quantitative measures are introduced to quantify the contribution of each of the oscillatory components involved on the time scale of up to three minutes. Oscillatory components are then analysed from signals obtained by simultaneous measurements of blood flow in the microcirculation, ECG, respiration and blood pressure. Based on quantitative evaluation of the oscillatory components related to (I) the heart beat (0.6-2Hz), (II) respiration (0.145-0.6Hz), (III) intrinsic myogenic activity (0.052-0.145Hz), (IV) sympathetic activity (0.021-0.052Hz), (V, VI) endothelial related activity (0.0095-0.021Hz, 0.005 - 0.0095 Hz), 30-minutes recording taken on 109 healthy subjects, 75 patients with diabetes, and 82 patients after acute myocardial infarction (AMI) were analysed. Classification of the effect of ageing, diabetes and AMI from blood flow signals simultaneously recorded in the skin of four extremities, the heart rate and heart rate variability from R-R intervals will be presented and discussed.

  13. Circulating Natural IgM Antibodies Against Angiogenin in the Peripheral Blood Sera of Patients with Osteosarcoma as Candidate Biomarkers and Reporters of Tumorigenesis

    PubMed Central

    Savitskaya, Yulia A.; Rico, Genaro; Linares, Luis; González, Roberto; Téllez, René; Estrada, Eréndira; Marín, Norma; Martínez, Elisa; Alfaro, Alfonso; Ibarra, Clemente

    2010-01-01

    Background: Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis. Objectives: To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers. Methods: Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans. Results: Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals (P < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the

  14. Identification of novel molecular markers for detection of gastric cancer cells in the peripheral blood circulation using genome-wide microarray analysis.

    PubMed

    Matsumura, Nobuyuki; Zembutsu, Hitoshi; Yamaguchi, Koji; Sasaki, Kazuaki; Tsuruma, Tetsuhiro; Nishidate, Toshihiko; Denno, Ryuichi; Hirata, Koichi

    2011-07-01

    Although metastasis or relapse is a leading cause of death for patients with gastric cancer, the hematogenous spread of cancer cells remains undetected at the time of initial therapy. The development of novel diagnostic molecular marker(s) to detect circulating gastric cancer cells is an issue of great clinical importance. We obtained peripheral blood samples from 10 patients with gastric cancer who underwent laparotomy and 4 healthy volunteers. Microarray analysis consisting of 30,000 genes or ESTs was carried out using eight gastric cancer tissues and normal gastric mucosae. We selected 53 genes up-regulated in gastric cancer compared to normal gastric mucosae from our microarray data set, and, among these, identified five candidate marker genes (TSPAN8, EPCAM, MMP12, MMP7 and REG3A) which were not expressed in peripheral blood mononuclear cells (PBMCs) from 4 healthy volunteers. We further carried out semi-quantitative nested reverse transcription-polymerase chain reaction (RT-PCR) for HRH1, EGFR, CK20 and CEA in addition to the five newly identified genes using PBMCs of patients with gastric cancer, and found that expression of one or more genes out of the nine was detected in 80% of the patients with gastric cancer. Moreover, the numbers of genes expressed in PBMCs were ≤2 and ≥2 in all vascular invasion-negative cases and in 5 of 6 positive cases, respectively, showing significant differences between the two groups (P=0.041). Nested RT-PCR analysis for the set of nine marker genes using PBMCs may provide the potential for detection of circulating gastric cancer cells prior to metastasis formation in other organs.

  15. Assessment of intermittent UMTS electromagnetic field effects on blood circulation in the human auditory region using a near-infrared system.

    PubMed

    Spichtig, Sonja; Scholkmann, Felix; Chin, Lydia; Lehmann, Hugo; Wolf, Martin

    2012-01-01

    The aim of the present study was to assess the potential effects of intermittent Universal Mobile Telecommunications System electromagnetic fields (UMTS-EMF) on blood circulation in the human head (auditory region) using near-infrared spectroscopy (NIRS) on two different timescales: short-term (effects occurring within 80 s) and medium-term (effects occurring within 80 s to 30 min). For the first time, we measured potential immediate effects of UMTS-EMF in real-time without any interference during exposure. Three different exposures (sham, 0.18 W/kg, and 1.8 W/kg) were applied in a controlled, randomized, crossover, and double-blind paradigm on 16 healthy volunteers. In addition to oxy-, deoxy-, and total haemoglobin concentrations ([O(2) Hb], [HHb], and [tHb], respectively), the heart rate (HR), subjective well-being, tiredness, and counting speed were recorded. During exposure to 0.18 W/kg, we found a significant short-term increase in Δ[O(2) Hb] and Δ[tHb], which is small (≈17%) compared to a functional brain activation. A significant decrease in the medium-term response of Δ[HHb] at 0.18 and 1.8 W/kg exposures was detected, which is in the range of physiological fluctuations. The medium-term ΔHR was significantly higher (+1.84 bpm) at 1.8 W/kg than for sham exposure. The other parameters showed no significant effects. Our results suggest that intermittent exposure to UMTS-EMF has small short- and medium-term effects on cerebral blood circulation and HR.

  16. Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay

    PubMed Central

    Schwaederle, Maria; Husain, Hatim; Fanta, Paul T.; Piccioni, David E.; Kesari, Santosh; Schwab, Richard B.; Banks, Kimberly C.; Lanman, Richard B.; Talasaz, AmirAli; Parker, Barbara A.; Kurzrock, Razelle

    2016-01-01

    Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent. PMID:26848768

  17. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron.

    PubMed

    Hod, Eldad A; Brittenham, Gary M; Billote, Genia B; Francis, Richard O; Ginzburg, Yelena Z; Hendrickson, Jeanne E; Jhang, Jeffrey; Schwartz, Joseph; Sharma, Shruti; Sheth, Sujit; Sireci, Anthony N; Stephens, Hannah L; Stotler, Brie A; Wojczyk, Boguslaw S; Zimring, James C; Spitalnik, Steven L

    2011-12-15

    Transfusions of RBCs stored for longer durations are associated with adverse effects in hospitalized patients. We prospectively studied 14 healthy human volunteers who donated standard leuko-reduced, double RBC units. One unit was autologously transfused "fresh" (3-7 days of storage), and the other "older" unit was transfused after 40 to 42 days of storage. Of the routine laboratory parameters measured at defined times surrounding transfusion, significant differences between fresh and older transfusions were only observed in iron parameters and markers of extravascular hemolysis. Compared with fresh RBCs, mean serum total bilirubin increased by 0.55 mg/dL at 4 hours after transfusion of older RBCs (P = .0003), without significant changes in haptoglobin or lactate dehydrogenase. In addition, only after the older transfusion, transferrin saturation increased progressively over 4 hours to a mean of 64%, and non-transferrin-bound iron appeared, reaching a mean of 3.2μM. The increased concentrations of non-transferrin-bound iron correlated with enhanced proliferation in vitro of a pathogenic strain of Escherichia coli (r = 0.94, P = .002). Therefore, circulating non-transferrin-bound iron derived from rapid clearance of transfused, older stored RBCs may enhance transfusion-related complications, such as infection.

  18. Preterm Birth Prevention: Effects of Vaginal Progesterone Administration on Blood Flow Impedance in Uterine-Fetal Circulation by Doppler Sonography

    PubMed Central

    Vafaei, Homeira; Zamanpour, Tarlan; Shahraki, Hadi Raeisi

    2016-01-01

    Objective: The present study aimed to evaluate the effect of vaginal progesterone administration on maternal and fetal circulation to prevent preterm birth. Methods: The present prospective study was conducted on 35 women with singleton pregnancy at 18–33 weeks of gestation, who presented with at least one episode of preterm labor or asymptomatic short cervix, or past medical history of preterm birth. Doppler flow and Pulsatility Index (PI) assessment of the umbilical artery, fetal middle cerebral artery, uterine arteries, and ductusvenosus were performed before and 72 h after vaginal progesterone administration. Results: Results showed a significant reduction in the PI of the uterine artery following progesterone administration. Nevertheless, no significant changes were observed in the PI of other vessels. No significant difference was found in Doppler flow parameters in any of the examined vessels before or after progesterone treatment in women with Preterm Labor Pain (PLP). Yet, a statistically significant association was observed between short cervix complication in the current pregnancy and medical history of PLP in the previous pregnancy. Conclusion: Treatment with vaginal progesterone reduced the PI in the uterine arteries in the second and third trimesters of pregnancy. Thus, this medication may have useful vasodilatory effects on uterine-fetal vessels. PMID:26925899

  19. 34 CFR 85.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Adequate evidence. 85.900 Section 85.900 Education Office of the Secretary, Department of Education GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 85.900 Adequate evidence. Adequate evidence means information sufficient to support...

  20. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  1. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  2. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  3. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  4. Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity.

    PubMed

    Broadley, Steven P; Plaumann, Ann; Coletti, Raffaele; Lehmann, Christin; Wanisch, Andreas; Seidlmeier, Amelie; Esser, Knud; Luo, Shanshan; Rämer, Patrick C; Massberg, Steffen; Busch, Dirk H; van Lookeren Campagne, Menno; Verschoor, Admar

    2016-07-13

    Efficient clearance of bacteremia prevents life-threatening disease. Platelet binding to intravascular bacteria, a process involving platelet glycoprotein GPIb and bacterial opsonization with activated complement C3, influences blood clearance and anti-infective immunity. Using intravital microscopy of the bloodstream of mice infected with Listeria monocytogenes, we show that bacterial clearance is not a uniform process but a "dual-track" mechanism consisting of parallel "fast" and "slow" pathways. "Slow clearance" is regulated by time-dependent bacterial opsonization, stochastic platelet binding, and capture of bacteria-platelet-complexes via the complement receptor of the immunoglobulin superfamily, CRIg. The mechanism spares some bacteria from "fast clearance" and rapid destruction in the liver via Kupffer cell scavenger receptors, keeping them available for adaptive immunity induction by splenic CD8α(+) dendritic cells. We consistently find "fast" and "slow" clearance patterns for a broad panel of other Gram+ and Gram- bacteria. Thus, dual-track clearance balances rapid restoration of blood sterility with induction of specific antibacterial immunity.

  5. Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity.

    PubMed

    Broadley, Steven P; Plaumann, Ann; Coletti, Raffaele; Lehmann, Christin; Wanisch, Andreas; Seidlmeier, Amelie; Esser, Knud; Luo, Shanshan; Rämer, Patrick C; Massberg, Steffen; Busch, Dirk H; van Lookeren Campagne, Menno; Verschoor, Admar

    2016-07-13

    Efficient clearance of bacteremia prevents life-threatening disease. Platelet binding to intravascular bacteria, a process involving platelet glycoprotein GPIb and bacterial opsonization with activated complement C3, influences blood clearance and anti-infective immunity. Using intravital microscopy of the bloodstream of mice infected with Listeria monocytogenes, we show that bacterial clearance is not a uniform process but a "dual-track" mechanism consisting of parallel "fast" and "slow" pathways. "Slow clearance" is regulated by time-dependent bacterial opsonization, stochastic platelet binding, and capture of bacteria-platelet-complexes via the complement receptor of the immunoglobulin superfamily, CRIg. The mechanism spares some bacteria from "fast clearance" and rapid destruction in the liver via Kupffer cell scavenger receptors, keeping them available for adaptive immunity induction by splenic CD8α(+) dendritic cells. We consistently find "fast" and "slow" clearance patterns for a broad panel of other Gram+ and Gram- bacteria. Thus, dual-track clearance balances rapid restoration of blood sterility with induction of specific antibacterial immunity. PMID:27345696

  6. Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer

    PubMed Central

    Nilsson, R. Jonas A.; Karachaliou, Niki; Berenguer, Jordi; Gimenez-Capitan, Ana; Schellen, Pepijn; Teixido, Cristina; Tannous, Jihane; Kuiper, Justine L.; Drees, Esther; Grabowska, Magda; van Keulen, Marte; Heideman, Danielle A.M.; Thunnissen, Erik; Dingemans, Anne-Marie C.; Viteri, Santiago; Tannous, Bakhos A.; Drozdowskyj, Ana; Rosell, Rafael; Smit, Egbert F.; Wurdinger, Thomas

    2016-01-01

    Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone. PMID:26544515

  7. Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance.

    PubMed

    Cao, Mei; Yie, Shang-Mian; Wu, Sheng-Min; Chen, Shu; Lou, Be; He, Xu; Ye, Shang-Rong; Xie, Ke; Rao, Lin; Gao, En; Ye, Nai-Yao

    2009-01-01

    We previously demonstrated that the detection of circulating cancer cells (CCC) expressing survivin mRNA could provide valuable information for predicting recurrence in patients with breast, lung, gastric and colorectal carcinoma. The purpose of this study is to investigate whether the detection of survivin-expressing CCC in the peripheral blood is also useful for predicting recurrence in patients with esophageal squamous cell carcinoma (ESCC). Blood samples obtained from 108 ESCC patients and 75 healthy volunteers were quantitatively investigated by a technique that detected reverse transcription-polymerase chain reaction products based on a hybridization-enzyme linked immunosorbent essay. Not all of the patients were available for the follow-up study. Only 48 patients who were treated with similar adjuvant therapy regimens were available and followed-up for 33 months after the initial assay test. Survivin-expressing CCC were detected in 51 (47.2%) patients. The presence of survivin-expressing CCC was found to be significantly associated with depth of invasion, vascular invasion, nodal status, and disease stages (P = 0.032, 0.019, 0.018, and 0.001, respectively). During the follow-up period, patients who had positive survivin expressions had a higher relapse rate and a shorter survival time than those who had negative survivin expressions (P = 0.002 and 0.016, respectively). Examination of survivin-expressing CCC could provide valuable information in the prediction of haematogenous recurrence as well as in the prognosis of ESCC. PMID:19521785

  8. Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review.

    PubMed

    Hennigar, Stephen R; Kelley, Alyssa M; McClung, James P

    2016-07-01

    Zinc is an essential nutrient for humans; however, a sensitive biomarker to assess zinc status has not been identified. The objective of this systematic review was to compile and assess studies that determined zinc transporter and/or metallothionein expression in various blood cell types and to determine their reliability and sensitivity to changes in dietary zinc. Sixteen studies were identified that determined the expression of zrt-, irt-like protein (ZIP) 1 [solute carrier family (SLC) 39A1], ZIP3 (SLC39A3), ZIP5 (SLC39A5), ZIP6 (SLC39A6), ZIP7 (SLC39A7), ZIP8 (SLC39A8), ZIP10 (SLC39A10), ZIP14 (SLC39A14), zinc transporter (ZnT)1 (SLC30A1), ZnT2 (SLC30A2), ZnT4 (SLC30A4), ZnT5 (SLC30A5), ZnT6 (SLC30A6), ZnT7 (SLC30A7), ZnT9 (SLC30A9), and/or metallothionein in various blood cells isolated from healthy adult men and women in response to zinc supplementation or depletion. Cell types included leukocytes, peripheral blood mononuclear cells, T lymphocytes, monocytes, and erythrocytes. ZIP1, ZnT1, and metallothionein were the most commonly measured proteins. Changes in ZIP1 and ZnT1 in response to zinc supplementation or depletion were not consistent across studies. Leukocyte metallothionein decreased with zinc depletion (-39% change from baseline, <5 mg Zn/d, n = 2 studies) and increased with zinc supplementation in a dose-dependent manner (35%, 15-22 mg Zn/d, n = 7 studies; 267%, 50 mg Zn/d, n = 2 studies) and at the earliest time points measured; however, no change or delayed response was observed in metallothionein in erythrocytes. A greater percentage of studies demonstrated that metallothionein in leukocyte subtypes was a more reliable (100%, n = 12; 69%, n = 16) and responsive (92%, n = 12; 82%, n = 11) indicator of zinc exposure than was plasma zinc, respectively. In conclusion, current evidence indicates that metallothionein in leukocyte subtypes may be a component in determining zinc status. PMID:27422508

  9. Implication of cerebral circulation time in intracranial stenosis measured by digital subtraction angiography on cerebral blood flow estimation measured by arterial spin labeling

    PubMed Central

    Jann, Kay; Hauf, Martinus; Kellner-Weldon, Frauke; El-Koussy, Marwan; Kiefer, Claus; Federspiel, Andrea; Schroth, Gerhard

    2016-01-01

    PURPOSE Arterial spin labeling (ASL) magnetic resonance imaging to assess cerebral blood flow (CBF) is of increasing interest in basic research and in diagnostic applications, since ASL provides similar information to positron emission tomography about perfusion in vascular territories. However, in patients with steno-occlusive arterial disease (SOAD), CBF as measured by ASL might be underestimated due to delayed bolus arrival, and thus increased spin relaxation. We aimed to estimate the extent to which bolus arrival time (BAT) was delayed in patients with SOAD and whether this resulted in underestimation of CBF. METHODS BAT was measured using digital subtraction angiography (DSA) in ten patients with high-grade stenosis of the middle carotid artery (MCA). Regional CBF was assessed with pseudocontinuous ASL. RESULTS BATs were nonsignificantly prolonged in the stenotic hemisphere 4.1±2.0 s compared with the healthy hemisphere 3.3±0.9 s; however, there were substantial individual differences on the stenotic side. CBF in the anterior and posterior MCA territories were significantly reduced on the stenotic hemisphere. Severe stenosis was correlated with longer BAT and lower quantified CBF. CONCLUSION ASL-based perfusion measurement involves a race between the decay of the spins and the delivery of labeled blood to the region of interest. Special caution is needed when interpreting CBF values quantified in individuals with altered blood flow and delayed circulation times. However, from a clinician’s point of view, an accentuation of hypoperfusion (even if caused by underestimation of CBF due to prolonged BATs) might be desirable since it indexes potentially harmful physiologic deficits. PMID:27411297

  10. Air pollution exposure affects circulating white blood cell counts in healthy subjects: the role of particle composition, oxidative potential and gaseous pollutants - the RAPTES project.

    PubMed

    Steenhof, Maaike; Janssen, Nicole A H; Strak, Maciej; Hoek, Gerard; Gosens, Ilse; Mudway, Ian S; Kelly, Frank J; Harrison, Roy M; Pieters, Raymond H H; Cassee, Flemming R; Brunekreef, Bert

    2014-02-01

    Studies have linked air pollution exposure to cardiovascular health effects, but it is not clear which components drive these effects. We examined the associations between air pollution exposure and circulating white blood cell (WBC) counts in humans. To investigate independent contributions of particulate matter (PM) characteristics, we exposed 31 healthy volunteers at five locations with high contrast and reduced correlations amongst pollutant components: two traffic sites, an underground train station, a farm and an urban background site. Each volunteer visited at least three sites and was exposed for 5 h with intermittent exercise. Exposure measurements on-site included PM mass and number concentration, oxidative potential (OP), elemental- and organic carbon, metals, O3 and NO2. Total and differential WBC counts were performed on blood collected before and 2 and 18 h post-exposure (PE). Changes in total WBC counts (2 and 18 h PE), number of neutrophils (2 h PE) and monocytes (18 h PE) were positively associated with PM characteristics that were high at the underground site. These time-dependent changes reflect an inflammatory response, but the characteristic driving this effect could not be isolated. Negative associations were observed for NO2 with lymphocytes and eosinophils. These associations were robust and did not change after adjustment for a large suite of PM characteristics, suggesting an independent effect of NO2. We conclude that short-term air pollution exposure at real-world locations can induce changes in WBC counts in healthy subjects. Future studies should indicate if air pollution exposure-induced changes in blood cell counts results in adverse cardiovascular effects in susceptible individuals.

  11. Clinical impact of circulating microRNAs as blood-based marker in childhood acute lymphoblastic leukemia.

    PubMed

    Swellam, Menha; El-Khazragy, Nashwa

    2016-08-01

    Aberrant microRNA (miRNA) expression participates in childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the expression of miRNA-100, miRNA-196a, and miRNA-146a among childhood ALL and study their correlation with other hematological parameters and different phenotypes. Peripheral blood mononuclear cells (PMNCs) were obtained from 85 childhood ALL and 25 healthy children for the detection of miRNA expression using quantitative real-time PCR. Significant higher median levels were reported for ALL compared to control children. The diagnostic efficacy for miRNA-146a was superior as both sensitivity and specificity were absolute. A significant correlation was observed between higher expression of miRNA-100 and lower platelet and lymphocyte counts; high expression of miRNA-146a showed significant correlation with low total leukocyte count (TLC) and lymphocyte counts. Significant relation was reported between studied miRNAs and different phenotyping. miRNA-100, miRNA-196a, and miRNA-146a have significant role in childhood ALL leukemogenesis, and they may be useful as biological diagnostic molecular markers. PMID:26857279

  12. Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent

    PubMed Central

    Starosolski, Zbigniew; Villamizar, Carlos A.; Rendon, David; Paldino, Michael J.; Milewicz, Dianna M.; Ghaghada, Ketan B.; Annapragada, Ananth V.

    2015-01-01

    Abnormalities in the cerebrovascular system play a central role in many neurologic diseases. The on-going expansion of rodent models of human cerebrovascular diseases and the need to use these models to understand disease progression and treatment has amplified the need for reproducible non-invasive imaging methods for high-resolution visualization of the complete cerebral vasculature. In this study, we present methods for in vivo high-resolution (19 μm isotropic) computed tomography imaging of complete mouse brain vasculature. This technique enabled 3D visualization of large cerebrovascular networks, including the Circle of Willis. Blood vessels as small as 40 μm were clearly delineated. ACTA2 mutations in humans cause cerebrovascular defects, including abnormally straightened arteries and a moyamoya-like arteriopathy characterized by bilateral narrowing of the internal carotid artery and stenosis of many large arteries. In vivo imaging studies performed in a mouse model of Acta2 mutations demonstrated the utility of this method for studying vascular morphometric changes that are practically impossible to identify using current histological methods. Specifically, the technique demonstrated changes in the width of the Circle of Willis, straightening of cerebral arteries and arterial stenoses. We believe the use of imaging methods described here will contribute substantially to the study of rodent cerebrovasculature. PMID:25985192

  13. Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome

    SciTech Connect

    Iriyama, Chisako; Tomita, Akihiro; Hoshino, Hideaki; Adachi-Shirahata, Mizuho; Furukawa-Hibi, Yoko; Yamada, Kiyofumi; Kiyoi, Hitoshi; Naoe, Tomoki

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Circulating DNAs (CDs) can be used to detect genetic/epigenetic abnormalities in MDS. Black-Right-Pointing-Pointer Epigenetic changes can be detected more sensitively when using plasma DNA than PBMNC. Black-Right-Pointing-Pointer Mutation ratio in CDs may reflect the ratio in stem cell population in bone marrow. Black-Right-Pointing-Pointer Using CDs can be a safer alternate strategy compared to bone marrow aspiration. -- Abstract: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3-9) using DNAs from plasma, serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic

  14. Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies

    PubMed Central

    2012-01-01

    Background Circulating tumor cells (CTCs) are detectable in peripheral blood of metastatic breast cancer patients (MBC). In this paper we evaluate a new CTC separation method based on a combination of anti-EpCAM- and anti-cytokeratin magnetic cell separation with the aim to improve CTC detection with low target antigen densities. Methods Blood samples of healthy donors spiked with breast cancer cell line HCC1937 were used to determine accuracy and precision of the method. 10 healthy subjects were examined to evaluate specificity. CTC counts in 59 patients with MBC were measured to evaluate the prognostic value on overall survival. Results Regression analysis of numbers of recovered vs. spiked HCC1937 cells yielded a coefficient of determination of R2 = 0.957. The average percentage of cell recovery was 84%. The average within-run coefficient of variation for spiking of 185, 85 and 30 cells was 14%. For spiking of 10 cells the within-run CV was 30%. No CTCs were detected in blood of 10 healthy subjects examined. A standard threshold of 5 CTC/7.5 ml blood as a cut-off point between risk groups led to a highly significant prognostic marker (p < 0.001). To assess the prognostic value of medium CTC levels we additionally considered a low (CTC-L: 0 CTC), a medium (CTC-M: 1–4 CTC) and a high risk group (CTC-H: ≥5 CTC). The effect of this CTC-LMH marker on overall survival was significant as well (p < 0.001). A log-ratio test performed to compare the model with 3 vs. the model with 2 risk groups rejected the model with 2 risk groups (p = 0.026). For CTC as a count variable, we propose an offset reciprocal transformation 1/(1 + x) for overall survival prediction (p < 0.001). Conclusions We show that our CTC detection method is feasible and leads to accurate and reliable results. Our data suggest that a refined differentiation between patients with different CTC levels is reasonable. PMID:22646670

  15. Circulating leptin and NF-κB activation in peripheral blood mononuclear cells across the menstrual cycle.

    PubMed

    Faustmann, Gernot; Tiran, Beate; Maimari, Theopisti; Kieslinger, Petra; Obermayer-Pietsch, Barbara; Gruber, Hans-Jürgen; Roob, Johannes M; Winklhofer-Roob, Brigitte M

    2016-07-01

    Using the menstrual cycle as a model, this study focused on longitudinal changes and associations within a physiological network known to play a role in female fertility, including, as biologically active nodes, NF-κB, leptin and adiponectin, β-carotene, adipose tissue, and progesterone. In 28 women, leptin, adiponectin, β-carotene, and progesterone concentrations, NF-κB p65 and p50 activation in peripheral blood mononuclear cells (known to possess estrogen, progesterone and leptin receptors), total body fat (TBF) and subcutaneous adipose tissue (SAT) mass were determined at early (T1) and late follicular (T2) and mid (T3) and late (T4) luteal phase. Leptin and adiponectin concentrations were higher, while NF-κB p65 activation was lower at T3 compared with T1. NF-κB p65 activation was inversely related to leptin concentrations at T1, T3, and T4. β-Carotene was inversely related to leptin (T1,T2,T4) and SAT (T1,T3,T4). NF-κB p50 activation was inversely related to TBF (T4) and SAT (T3,T4), and leptin was positively related to TBF and SAT (T1-T4). Progesterone was inversely related to leptin (T2,T3), adiponectin (T3), TBF (T3,T4), and SAT (T2,T3,T4). By providing evidence of luteal phase-specific reduced NF-κB p65 activation in women under physiological conditions, this study bridges the gap between existing evidence of a Th1-Th2 immune response shift induced by reduced NF-κB p65 activation and a Th1-Th2 shift previously observed at luteal phase. For the first time, inverse regressions suggest inhibitory effects of leptin on NF-κB p65 activation at luteal phase, along with inhibitory effects of leptin as well as adiponectin on progesterone production in corpus luteum. © 2016 The Authors BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology. 24(4):376-387, 2016. PMID:27093900

  16. [Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

    PubMed

    Lü, Ming; Wang, Tai-yi; Tian, Xiao-xuan; Shi, Xin-hui; Fan, Guan-wei; Zhang, Yan; Zhu, Yan

    2015-09-01

    Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS. PMID:26757550

  17. [Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

    PubMed

    Lü, Ming; Wang, Tai-yi; Tian, Xiao-xuan; Shi, Xin-hui; Fan, Guan-wei; Zhang, Yan; Zhu, Yan

    2015-09-01

    Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.

  18. Hemorheology and circulation.

    PubMed

    Marossy, A; Svorc, P; Kron, I; Gresová, S

    2009-01-01

    The main functions of the blood are the transport, and delivery of oxygen and nutrients, removal of carbon dioxide and waste products of metabolism, distribution of heat and signals of immune system. They are provided by circulation due to the driving force of the heart. Circulation of the blood depends on its rheological properties of the blood as well as on characteristics of the vessels through which the blood passes. The blood flow resistance is influenced by the complicated architecture of the vascular network and flow behaviour of blood components - blood cells and plasma. The obtained data based on analysis of influences on blood flow are differentiated in the dependence on place and level of investigation. At a macroscopic level the blood appears to be a liquid material, but at a microscopic level the blood appears to be a material with microscopic solid particles of varying size - various blood cells. From this point of view, we have to consider the blood flow in large vessels, and also on the level of microvessels. This division of facts of hemorheology is somewhat simplistic, but is very useful from the point of view of explanation and comprehension. PMID:19628890

  19. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood.

    PubMed

    Escolar, Gines; Fernandez-Gallego, Victor; Arellano-Rodrigo, Eduardo; Roquer, Jaume; Reverter, Joan Carles; Sanz, Victoria Veronica; Molina, Patricia; Lopez-Vilchez, Irene; Diaz-Ricart, Maribel; Galan, Ana Maria

    2013-01-01

    Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s(-1). The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM

  20. Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation – Description of a novel in vitro model

    SciTech Connect

    Ehnert, Sabrina; Freude, Thomas; Ihle, Christoph; Mayer, Larissa; Braun, Bianca; Graeser, Jessica; Flesch, Ingo; and others

    2015-03-15

    Type 2 diabetes mellitus (T2DM) is one of the most frequent metabolic disorders in industrialized countries. Among other complications, T2DM patients have an increased fracture risk and delayed fracture healing. We have demonstrated that supraphysiological glucose and insulin levels inhibit primary human osteoblasts' maturation. We aimed at developing a more physiologically relevant in vitro model to analyze T2DM-mediated osteoblast changes. Therefore, SCP-1-immortalized pre-osteoblasts were differentiated with T2DM or control (non-obese and obese) sera. Between both control groups, no significant changes were observed. Proliferation was significantly increased (1.69-fold), while AP activity and matrix mineralization was significantly reduced in the T2DM group. Expression levels of osteogenic marker genes and transcription factors were altered, e.g. down-regulation of RUNX2 and SP-7 or up-regulation of STAT1, in the T2DM group. Active TGF-β levels were significantly increased (1.46-fold) in T2DM patients' sera. SCP-1 cells treated with these sera showed significantly increased TGF-β signaling (2.47-fold). Signaling inhibition effectively restored osteoblast maturation in the T2DM group. Summarizing our data, SCP-1 cells differentiated in the presence of T2DM patients' serum exhibit reduced osteoblast function. Thus, this model has a high physiological impact, as it can identify circulating factors in T2DM patients' blood that may affect bone function, e.g. TGF-β. - Highlights: • We present here a physiologically relevant in vitro model for diabetic osteopathy. • Blood of T2DM patients contains factors that affect osteoblasts' function. • The model developed here can be used to identify these factors, e.g. TGF-β. • Blocking TGF-β signaling partly rescues the osteoblasts' function in the T2DM group. • The model is useful to demonstrate the role of single factors in diabetic osteopathy.

  1. First hepatitis B virus full-length genomic study among blood donors from Argentina: unexpected mutations in the circulating subgenotypes' proteins.

    PubMed

    Delfino, C M; Berini, C; Pedrozo, W; Malan, R; Blejer, J; Oubiña, J R; Biglione, M M; Mathet, V L

    2015-04-01

    Hepatitis B virus (HBV) is a worldwide public health concern. The circulation of strains carrying mutations in the viral proteins implies both clinical and therapeutics challenges. HBV complete genomes (HBV-CGs) were reported from injecting drug users and HBV chronically infected patients from Argentina-including Amerindians-although no studies were conducted in blood donors. Here, we described HBV-CG sequences from the latter population. Some of the HBV sequences classified as B2 and C2 subgenotypes clustering together with Asian isolates, while others, such as D3, F1b, and F4, were homologous to European and Latin America sequences. New substitutions for all analyzed open reading frames and changes in the HBsAg hydrophobicity profiles were detected. Several HBV-CG subgenotypes are described for the first time in this population. Mutations observed in X, PreS, and P proteins have been associated with advanced liver disease, hepatocellular carcinoma, and/or natural resistance to nucleos(t)ide antiviral treatment. It deserves to be highlighted that these substitutions were detected in a population without epidemiological risk factors for viral infection, and most importantly, without any previous antiviral treatment (natural resistance). Regarding the remaining mutations, further research is warranted in order to determine their clinical and therapeutics relevance. PMID:25537951

  2. Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: Effect on outcome.

    PubMed

    Chan, Adeline; Yan, Jun; Csurhes, Peter; Greer, Judith; McCombe, Pamela

    2015-09-15

    The aim of this study was to measure the levels of circulating BDNF and the frequency of BDNF-producing T cells after acute ischaemic stroke. Serum BDNF levels were measured by ELISA. Flow cytometry was used to enumerate peripheral blood leukocytes that were labelled with antibodies against markers of T cells, T regulatory cells (Tregs), and intracellular BDNF. There was a slight increase in serum BDNF levels after stroke. There was no overall difference between stroke patients and controls in the frequency of CD4(+) and CD8(+) BDNF(+) cells, although a subgroup of stroke patients showed high frequencies of these cells. However, there was an increase in the percentage of BDNF(+) Treg cells in the CD4(+) population in stroke patients compared to controls. Patients with high percentages of CD4(+) BDNF(+) Treg cells had a better outcome at 6months than those with lower levels. These groups did not differ in age, gender or initial stroke severity. Enhancement of BDNF production after stroke could be a useful means of improving neuroprotection and recovery after stroke.

  3. Intrinsic determinants and predictors of superovulatory yields in sheep: Circulating concentrations of reproductive hormones, ovarian status, and antral follicular blood flow.

    PubMed

    Bartlewski, Pawel M; Seaton, Patricia; Franco Oliveira, Maria Emilia; Kridli, Rami T; Murawski, Maciej; Schwarz, Tomasz

    2016-07-01

    Hormonal ovarian superstimulation has contributed to small ruminant reproduction around the world, impacting genetic improvement and zoosanitary programs, contributing to the conservation of endangered species, and supporting other related biotechnologies. Advanced knowledge surrounding the superovulatory treatments in sheep has resulted in enhanced control of influencing factors and improved the protocols currently used. However, in spite of minimization of some adverse factors, superovulatory responses in ewes still remain variable, preventing the more widespread use of superovulation in commercial embryo transfer programs and reproductive research in this species. Recent evidence demonstrates that changes in antral follicular populations and blood supply, and circulating concentrations of certain reproductive hormones determined at the specific time points just before or during the superovulatory treatment are associated with superovulation success in ewes. This review attempts to compile the data from available literature to identify ovarian and hormonal determinants of the superovulatory outcome in ewes, which can be used to substantially improve the existing protocols and to reduce the extra cost and unnecessary stress imposed on poorly responding animals. An overview of most commonly used and some recently developed, FSH-based ovarian stimulation protocols is given at the outset to highlight variation in the frequency and timing of gonadotropin injections, estrus synchronization methods, and follicular wave synchronization and/or ovulation induction techniques during the superovulatory treatments in ewes. PMID:27173957

  4. Fetal Circulation

    MedlinePlus

    ... Blood Pressure Prevention & Treatment of High Blood Pressure High ... will do after birth. The placenta accepts the bluest blood (blood without oxygen) from the fetus through blood vessels that leave ...

  5. Blood Supply.

    PubMed

    Kubo, Keitaro

    2016-01-01

    It has been suggested that blood circulation within the tendons contributes to repair of the tendon after the exercises. Recently, blood circulation of human tendons could be measured using red laser lights (Kubo et al. 2008b). Using this technique, we were able to measure changes in blood volume and oxygen saturation of human tendons by various treatments. During a 60-min heating, the blood volume and oxygen saturation of the tendon increased significantly from the resting level, and continued to increase by 35 min. These changes in blood circulation of tendon were considerably different from the temperatures of muscle and skin. Furthermore, when the needle tip was moved up and down from the targeted depth (up-and-down manipulation) at approximately 1 mm amplitude, the blood volume and oxygen saturation of the treated tendon increased significantly. After the removal of the acupuncture needle, the blood volume and oxygen saturation of the tendon increased gradually for the non-treated side. These results suggested that the change in blood circulation of the tendon during acupuncture with up-and-down manipulation was caused by axon reflex, and increase in blood flow in the tendons after the needle removal might be caused through the central nervous system. It is well known that heating and acupuncture treatments were quite effective in the management of tendon injuries. Therefore, these phenomena would be related to the changes in blood circulation of tendons due to heating and acupuncture treatments. PMID:27535246

  6. Blood Supply.

    PubMed

    Kubo, Keitaro

    2016-01-01

    It has been suggested that blood circulation within the tendons contributes to repair of the tendon after the exercises. Recently, blood circulation of human tendons could be measured using red laser lights (Kubo et al. 2008b). Using this technique, we were able to measure changes in blood volume and oxygen saturation of human tendons by various treatments. During a 60-min heating, the blood volume and oxygen saturation of the tendon increased significantly from the resting level, and continued to increase by 35 min. These changes in blood circulation of tendon were considerably different from the temperatures of muscle and skin. Furthermore, when the needle tip was moved up and down from the targeted depth (up-and-down manipulation) at approximately 1 mm amplitude, the blood volume and oxygen saturation of the treated tendon increased significantly. After the removal of the acupuncture needle, the blood volume and oxygen saturation of the tendon increased gradually for the non-treated side. These results suggested that the change in blood circulation of the tendon during acupuncture with up-and-down manipulation was caused by axon reflex, and increase in blood flow in the tendons after the needle removal might be caused through the central nervous system. It is well known that heating and acupuncture treatments were quite effective in the management of tendon injuries. Therefore, these phenomena would be related to the changes in blood circulation of tendons due to heating and acupuncture treatments.

  7. Female rats release more corticosterone than males in response to alcohol: influence of circulating sex steroids and possible consequences for blood alcohol levels.

    PubMed

    Rivier, C

    1993-08-01

    The hypothalamic-pituitary-adrenal (HPA) axis of female rats is more responsive to a variety of stimuli than that of males. Proestrous females are also reported to release more ACTH and corticosterone in response to restraint stress than females at other stages of the estrous cycle. Finally, blood alcohol levels (BALs) reached in response to a standard dose of alcohol also indicate the presence of a gender specificity, with females exhibiting higher BALs than males. The aim of this study was therefore 2-fold: first, we investigated the influence of gender on the ability of alcohol to increase plasma ACTH and corticosterone secretion in the rat. Second, we tested the hypothesis that corticosterone alters alcohol metabolism and asked whether this might represent a mechanism underlying the sex difference in BALs. We observed that compared with intact males, intact females taken at random stages of the estrous cycle secreted significantly (p < 0.01) more ACTH and corticosterone in response to alcohol (0.2-1.8 g/kg). Within females, the intraperitoneal administration of alcohol was followed by higher plasma ACTH and corticosteroids levels during proestrus and estrus, compared with diestrus. Removal of circulating sex steroids abolished the gender difference in terms of ACTH secretion, but ovariectomized females still released more corticosterone than castrated males in response to 0.6 and 1.8 g alcohol/kg. This difference could not be explained by a sex-related component of pituitary responsiveness to corticotropin-releasing factor.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Allogeneic Blood Product Usage in Coronary Artery Bypass Grafting (CABG) with minimalized Extracorporeal Circulation System (MECC) Versus Standard On-Pump Coronary Artery Bypass Grafting

    PubMed Central

    Lisy, M.; Schmid, E.; Kozok, J.; Rosenberger, P.; Stock, U.A.; Kalender, G.

    2016-01-01

    Aim: Intraoperative allogeneic blood product transfusion (ABPT) in cardiac surgery is associated with worse overall outcome, including mortality. The objective of this study was to evaluate the ABPTs in minimalized extracorporeal cardiopulmonary (MECCTM) compared with standard open system on-pump coronary revascularization. Methods: Data of 156 patients undergoing myocardial revascularization between September 2008 and September 2010 were reviewed. 83 patients were operated by the MECC technique and 73 were treated by standard extracorporeal circulation (sECC). ABPT and overall early postoperative complications were analyzed. Results: Operative mortality and morbidity were similar in both groups. ABPT in the MECC group was significantly lower than in the sECC group both intraoperatively (7.2 vs. 60.3% of patients p<0.001) and during the first five postoperative days (19.3 vs. 57.5%; p<0.001). “Skin to skin”- (214 ± 45 vs. 232 ± 45 min; p=0.012), cardiopulmonary bypass (CPB) - (82 ± 25 vs. 95 ± 26 min; p=0.014), and X-clamp- times (50 ± 16 vs. 56 ± 17 min; p=0.024) were significantly lower in the MECC group than in the sECC group. Length of ICU (intensive care unit) - and hospital stay were also significantly lower in the MECC group vs. the sECC group (26.7 ± 20.2 vs. 54.5 ± 68.9 h; p<0.001, and 12.0 ± 4.1 vs. 14.5 ± 4.6 days; p<0.001). Conclusion: Application of MECC as on-pump coronary artery bypass graft (CABG) results in significantly lower ABPT as well as shorter ICU and in-hospital stay. In order to achieve these benefits of MECC autologous retrograde priming, Bispectral index (BIS) monitoring, intraoperative cell salvage, meticulous hemostasis and strict peri- and postoperative volume management are crucial. PMID:27499818

  9. The theory of the circulation of blood and (different) paths of Aristotelianism. Girolamo Franzosi's De motu cordis et sanguinis in animalibus pro Aristotele et Galeno adversus anatomicos neotericos libri duo: teleology versus mechanism?

    PubMed

    Lo Presti, Roberto

    2014-01-01

    Few discoveries in the history of medicine had a greater impact than William Harvey's discovery of the circulation of blood, and few intellectual milieus of the early modern period had as decisive a part in the rise of 'modern' medicine and the shaping of the western scientific mentality in general than the philosophical and scientific movement of 'Venetian Aristotelianism', which grew up around the University of Padua, where Harvey himself had studied. In this chapter, I aim to explore some aspects of the intellectual movement of 'Venetian Aristotelianism' as well as the debate that ensued upon the discovery of the circulation of blood. My focus, however, is not on any of the major protagonists, but rather on a quite marginal figure in this debate, namely Hieronymus Franzosi. PMID:25707099

  10. The theory of the circulation of blood and (different) paths of Aristotelianism. Girolamo Franzosi's De motu cordis et sanguinis in animalibus pro Aristotele et Galeno adversus anatomicos neotericos libri duo: teleology versus mechanism?

    PubMed

    Lo Presti, Roberto

    2014-01-01

    Few discoveries in the history of medicine had a greater impact than William Harvey's discovery of the circulation of blood, and few intellectual milieus of the early modern period had as decisive a part in the rise of 'modern' medicine and the shaping of the western scientific mentality in general than the philosophical and scientific movement of 'Venetian Aristotelianism', which grew up around the University of Padua, where Harvey himself had studied. In this chapter, I aim to explore some aspects of the intellectual movement of 'Venetian Aristotelianism' as well as the debate that ensued upon the discovery of the circulation of blood. My focus, however, is not on any of the major protagonists, but rather on a quite marginal figure in this debate, namely Hieronymus Franzosi.

  11. Asbestos/NESHAP adequately wet guidance

    SciTech Connect

    Shafer, R.; Throwe, S.; Salgado, O.; Garlow, C.; Hoerath, E.

    1990-12-01

    The Asbestos NESHAP requires facility owners and/or operators involved in demolition and renovation activities to control emissions of particulate asbestos to the outside air because no safe concentration of airborne asbestos has ever been established. The primary method used to control asbestos emissions is to adequately wet the Asbestos Containing Material (ACM) with a wetting agent prior to, during and after demolition/renovation activities. The purpose of the document is to provide guidance to asbestos inspectors and the regulated community on how to determine if friable ACM is adequately wet as required by the Asbestos NESHAP.

  12. [Experience in the use and comparative assessment of the effectiveness of crystalloid and blood cardioplegia].

    PubMed

    Kuznetsov, S V; Gritsenko, V V; Doĭnikov, D N; Mochalov, O Iu; Sharafutdinov, V E

    2001-01-01

    Due to an increasing attention to questions of adequate protection of the myocardium and widely spread use of the method of blood cardioplegia the authors have made a comparative analysis of effectiveness of using 2 methods of cardioplegia--pharmacocrystalloid and cool blood antegrade cardioplegia: 34 patients were operated upon under conditions of extracorporeal blood circulation for aortic and mitral valve replacement. A comparison was made of 17 patients with intermittent antegrade cool crystalloid cardioplegia (group 1) and 17 patients with intermittent antegrade cold blood cardioplegia (group II). The results have shown that intermittent antegrade cool blood cardioplegia is a safe and effective method for myocardial protection during cardiopulmonary bypass. PMID:11837000

  13. Supervision of Student Teachers: How Adequate?

    ERIC Educational Resources Information Center

    Dean, Ken

    This study attempted to ascertain how adequately student teachers are supervised by college supervisors and supervising teachers. Questions to be answered were as follows: a) How do student teachers rate the adequacy of supervision given them by college supervisors and supervising teachers? and b) Are there significant differences between ratings…

  14. Small Rural Schools CAN Have Adequate Curriculums.

    ERIC Educational Resources Information Center

    Loustaunau, Martha

    The small rural school's foremost and largest problem is providing an adequate curriculum for students in a changing world. Often the small district cannot or is not willing to pay the per-pupil cost of curriculum specialists, specialized courses using expensive equipment no more than one period a day, and remodeled rooms to accommodate new…

  15. Toward More Adequate Quantitative Instructional Research.

    ERIC Educational Resources Information Center

    VanSickle, Ronald L.

    1986-01-01

    Sets an agenda for improving instructional research conducted with classical quantitative experimental or quasi-experimental methodology. Includes guidelines regarding the role of a social perspective, adequate conceptual and operational definition, quality instrumentation, control of threats to internal and external validity, and the use of…

  16. An Adequate Education Defined. Fastback 476.

    ERIC Educational Resources Information Center

    Thomas, M. Donald; Davis, E. E. (Gene)

    Court decisions historically have dealt with educational equity; now they are helping to establish "adequacy" as a standard in education. Legislatures, however, have been slow to enact remedies. One debate over education adequacy, though, is settled: Schools are not financed at an adequate level. This fastback is divided into three sections.…

  17. Funding the Formula Adequately in Oklahoma

    ERIC Educational Resources Information Center

    Hancock, Kenneth

    2015-01-01

    This report is a longevity, simulational study that looks at how the ratio of state support to local support effects the number of school districts that breaks the common school's funding formula which in turns effects the equity of distribution to the common schools. After nearly two decades of adequately supporting the funding formula, Oklahoma…

  18. Core Bioactive Components Promoting Blood Circulation in the Traditional Chinese Medicine Compound Xueshuantong Capsule (CXC) Based on the Relevance Analysis between Chemical HPLC Fingerprint and In Vivo Biological Effects

    PubMed Central

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei

    2014-01-01

    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  19. Core bioactive components promoting blood circulation in the traditional Chinese medicine compound xueshuantong capsule (CXC) based on the relevance analysis between chemical HPLC fingerprint and in vivo biological effects.

    PubMed

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei

    2014-01-01

    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  20. Core bioactive components promoting blood circulation in the traditional Chinese medicine compound xueshuantong capsule (CXC) based on the relevance analysis between chemical HPLC fingerprint and in vivo biological effects.

    PubMed

    Liu, Hong; Liang, Jie-ping; Li, Pei-bo; Peng, Wei; Peng, Yao-yao; Zhang, Gao-min; Xie, Cheng-shi; Long, Chao-feng; Su, Wei-wei

    2014-01-01

    Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and

  1. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  2. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    PubMed Central

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J.T.

    2013-01-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. PMID:23585459

  3. Comparative metabolomics analysis on invigorating blood circulation for herb pair Gui-Hong by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and pattern recognition approach.

    PubMed

    Li, Shujiao; Lin, Hang; Tang, Yuping; Li, Weixia; Shen, Juan; Kai, Jun; Yue, Shijun; Shang, Guanxiong; Zhu, Zhenhua; Shang, Erxin; Zhang, Changbin; Zhang, Li; Yan, Hui; Liu, Pei; Duan, Jin-ao

    2015-03-25

    The compatibility of Angelicae Sinensis Radix (Danggui, DG) and Flos Carthami (Honghua, HH), a famous herb pair Gui-Hong (GH), can produce synergistic and promoting blood effects. Although some physiological and pathological function parameters of the acute blood stasis have been investigated, little information about the changes of small metabolites in biofluids has been reported. In present study, global metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) combined with pattern recognition method was performed to discover the underlying blood-activating regulation mechanisms of DG, HH and GH on the acute blood stasis rats induced by subcutaneous injection of adrenaline hydrochloride and ice water bath. The total 14 metabolites (10 in urine and 4 in plasma), up regulated or down regulated (P<0.05 or 0.01), were identified and contributed to the acute blood stasis progress. These promising identified biomarkers underpin the metabolic pathway including phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism and arginine and proline metabolism are disturbed in the acute blood stasis rats, which identified by using pathway analysis with MetPA. The altered metabolites and hemorheological indexes could be regulated closer to normal level after DG, HH and GH intervention. In term of activate blood circulation function, GH was the most effective as shown by the relative distance in PLS-DA score plots and relative intensity of metabolomics trategy, reflecting the synergic action between Danggui and Honghua. The results demonstrated that biofluids metabolomics was a powerful tool in clinical diagnosis and treatment of syndrome of blood stasis for providing information on changes in metabolites pathways. PMID:25668798

  4. [Nitric oxide production at pregnant rats and feature postnatal systemogenesis at their posterity developing at insufficiency of disturbance of utero-placental blood circulation].

    PubMed

    Nazarov, S B; Ivanova, A S; Novicov, A A

    2013-01-01

    Disturbance of uteroplacental circulation at white rats considerably reduces percent of survival rate of posterity. Hyperfunction of erythrocyte system and NO-dependent mechanisms of regulation in the first days of pups' life results in an exhaustion of their functional reserves.

  5. Is a vegetarian diet adequate for children.

    PubMed

    Hackett, A; Nathan, I; Burgess, L

    1998-01-01

    The number of people who avoid eating meat is growing, especially among young people. Benefits to health from a vegetarian diet have been reported in adults but it is not clear to what extent these benefits are due to diet or to other aspects of lifestyles. In children concern has been expressed concerning the adequacy of vegetarian diets especially with regard to growth. The risks/benefits seem to be related to the degree of restriction of he diet; anaemia is probably both the main and the most serious risk but this also applies to omnivores. Vegan diets are more likely to be associated with malnutrition, especially if the diets are the result of authoritarian dogma. Overall, lacto-ovo-vegetarian children consume diets closer to recommendations than omnivores and their pre-pubertal growth is at least as good. The simplest strategy when becoming vegetarian may involve reliance on vegetarian convenience foods which are not necessarily superior in nutritional composition. The vegetarian sector of the food industry could do more to produce foods closer to recommendations. Vegetarian diets can be, but are not necessarily, adequate for children, providing vigilance is maintained, particularly to ensure variety. Identical comments apply to omnivorous diets. Three threats to the diet of children are too much reliance on convenience foods, lack of variety and lack of exercise.

  6. [Efficacy of troxerutin on the flow properties of blood under defined conditions of circulation. A double-blind study of patients with diabetic retinopathy and arteriosclerotic retinopathy].

    PubMed

    Gallasch, G; Dörfer, C; Schmitt, T; Stage, A

    1985-07-01

    In a clinically controlled double-blind study it was demonstrated that tri-(hydroxyethyl)-rutin is not capable of significantly improving blood viscosity or one of its constituent factors. On the basis of data from 58 patients, none of whom was under 43 years old, it was possible to show that the substance tested has no favorable influence on plasma viscosity, erythrocyte deformability and aggregation, or on the concentration of plasma proteins which promote aggregation. Thus, in the very group of patients for whom an improvement in blood flow properties by means of oral administration of tri-(hydroxyethyl)rutin had been hoped for, no therapeutic effect could be demonstrated.

  7. Quantification of damage due to low-dose radiation exposure in mice: construction and application of a biodosimetric model using mRNA indicators in circulating white blood cells

    PubMed Central

    Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko; Tanaka, Mika; Yokochi, Kazuko; Fukutsu, Kumiko; Tajima, Katsushi; Nishimura, Mayumi; Shimada, Yoshiya; Akashi, Makoto

    2016-01-01

    Biodosimetry, the measurement of radiation damage in a biologic sample, is a reliable tool for increasing the accuracy of dose estimation. Although established chromosome analyses are suitable for estimating the absorbed dose after high-dose irradiation, biodosimetric methodology to measure damage following low-dose exposure is underdeveloped. RNA analysis of circulating blood containing radiation-sensitive cells is a candidate biodosimetry method. Here we quantified RNA from a small amount of blood isolated from mice following low-dose body irradiation (<0.5 Gy) aimed at developing biodosimetric tools for situations that are difficult to study in humans. By focusing on radiation-sensitive undifferentiated cells in the blood based on Myc RNA expression, we quantified the relative levels of RNA for DNA damage-induced (DDI) genes, such as Bax, Bbc3 and Cdkn1a. The RNA ratios of DDI genes/Myc in the blood increased in a dose-dependent manner 4 h after whole-body irradiation at doses ranging from 0.1 to 0.5 Gy (air-kerma) of X-rays, regardless of whether the mice were in an active or resting state. The RNA ratios were significantly increased after 0.014 Gy (air-kerma) of single X-ray irradiation. The RNA ratios were directly proportional to the absorbed doses in water ranging from 0.1 to 0.5 Gy, based on gamma-irradiation from 137Cs. Four hours after continuous irradiation with gamma-rays or by internal contamination with a beta-emitter, the increased RNA ratios resembled those following single irradiation. These findings indicate that the RNA status can be utilized as a biodosimetric tool to estimate low-dose radiation when focusing on undifferentiated cells in blood. PMID:26589759

  8. Adequate mathematical modelling of environmental processes

    NASA Astrophysics Data System (ADS)

    Chashechkin, Yu. D.

    2012-04-01

    In environmental observations and laboratory visualization both large scale flow components like currents, jets, vortices, waves and a fine structure are registered (different examples are given). The conventional mathematical modeling both analytical and numerical is directed mostly on description of energetically important flow components. The role of a fine structures is still remains obscured. A variety of existing models makes it difficult to choose the most adequate and to estimate mutual assessment of their degree of correspondence. The goal of the talk is to give scrutiny analysis of kinematics and dynamics of flows. A difference between the concept of "motion" as transformation of vector space into itself with a distance conservation and the concept of "flow" as displacement and rotation of deformable "fluid particles" is underlined. Basic physical quantities of the flow that are density, momentum, energy (entropy) and admixture concentration are selected as physical parameters defined by the fundamental set which includes differential D'Alembert, Navier-Stokes, Fourier's and/or Fick's equations and closing equation of state. All of them are observable and independent. Calculations of continuous Lie groups shown that only the fundamental set is characterized by the ten-parametric Galilelian groups reflecting based principles of mechanics. Presented analysis demonstrates that conventionally used approximations dramatically change the symmetries of the governing equations sets which leads to their incompatibility or even degeneration. The fundamental set is analyzed taking into account condition of compatibility. A high order of the set indicated on complex structure of complete solutions corresponding to physical structure of real flows. Analytical solutions of a number problems including flows induced by diffusion on topography, generation of the periodic internal waves a compact sources in week-dissipative media as well as numerical solutions of the same

  9. [THE PROFILE OF SEASONALITY OF MORTALITY OF DISEASES OF BLOOD CIRCULATION SYSTEM IN WOMEN IN RURAL TERRITORY OF THE REPUBLIC OF TATARSTAN].

    PubMed

    Kamalova, F M; Valeeva, E R

    2015-01-01

    The tasks of decreasing of mortality due to main causes require informational analytical support for effective decision making. The profiles of monthly mortality of women because of diseases of blood circular system vary in administrative territorial agglomerations with different social economical level. The monitoring of indicators of mortality permits selecting months of risk and to implement preventive, rehabilitation activities to decrease mortality.

  10. Effects of a TASER® conducted energy weapon on the circulating red-blood-cell population and other factors in Sus scrofa.

    PubMed

    Jauchem, James R; Bernhard, Joshua A; Cerna, Cesario Z; Lim, Tiffany Y; Seaman, Ronald L; Tarango, Melissa

    2013-09-01

    In previous studies hematocrit has been consistently increased in an anesthetized animal model after exposures to TASER(®) conducted energy weapons (CEWs). In the present study we analyzed changes in blood cell counts and red blood cell membrane proteins following two 30-s applications of a TASER C2 device (which is designed for civilian use). Hematocrit increased significantly from 33.2 ± 2.4 (mean ± SD) to 42.8 ± 4.6 % immediately after CEW exposure of eleven pigs (Sus scrofa). Red blood cell count increased significantly from 6.10 ± 0.55 × 10(12)/L to 7.45 ± 0.94 × 10(12)/L, and mean corpuscular volume increased significantly from 54.5 ± 2.4 fl to 57.8 ± 2.6 fl. Mean corpuscular hemoglobin concentration decreased significantly from 20.5 ± 0.7 to 18.5 ± 0.6 mM. Thirty protein spots (from two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis, selected for detailed comparison) exhibited greater densities 30-min post-exposure compared with pre-exposure values. A greater number of echinocytes were observed following CEW exposure. On the basis of these results it appears that, during the strong muscle contractions produced by TASER CEWs, a specific population of red blood cells (RBCs) may be released from the spleen or other reservoirs within the body. The total time of CEW exposure in the present study was relatively long compared with exposures in common law-enforcement scenarios. Despite statistically significant changes in red blood cell counts (and other measures directly related to RBCs), the alterations were short-lived. The transient nature of the changes would be likely to counteract any potentially detrimental effects.

  11. Reflex control of the circulation during exercise.

    PubMed

    Fadel, P J

    2015-12-01

    Appropriate cardiovascular and hemodynamic adjustments are necessary to meet the metabolic demands of working skeletal muscle during exercise. Alterations in the sympathetic and parasympathetic branches of the autonomic nervous system are fundamental in ensuring these adjustments are adequately made. Several neural mechanisms are responsible for the changes in autonomic activity with exercise and through complex interactions, contribute to the cardiovascular and hemodynamic changes in an intensity-dependent manner. This short review is from a presentation made at the Saltin Symposium June 2-4, 2015 in Copenhagen, Denmark. As such, the focus will be on reflex control of the circulation with an emphasis on the work of the late Dr. Bengt Saltin. Moreover, a concerted effort is made to highlight the novel and insightful concepts put forth by Dr. Saltin in his last published review article on the regulation of skeletal muscle blood flow in humans. Thus, the multiple roles played by adenosine triphosphate (ATP) including its ability to induce vasodilatation, override sympathetic vasoconstriction and stimulate skeletal muscle afferents (exercise pressor reflex) are discussed and a conceptual framework is set suggesting a major role of ATP in blood flow regulation during exercise.

  12. An electron paramagnetic resonance investigation of the oxygen dependence of the arterial-venous gradient of nitrosyl hemoglobin in blood circulation.

    PubMed

    Jiang, JinJie; Corbett, Jean; Hogg, Neil; Mason, Ronald P

    2007-10-15

    Whether there is a nitrosyl hemoglobin (HbNO) gradient between the venous and the arterial parts of the circulatory system is a very controversial issue in nitric oxide research. We have carefully evaluated the measurement of HbNO concentration in blood using EPR generated in vivo by the NO donor DEANO under various oxygen tensions. We found that the absolute concentrations of HbNO in venous and arterial blood were the same within experimental error, independent of hemoglobin saturation; only the ratios of 5-coordinate and 6-coordinate HbNO differed. The HbNO concentration increased when the oxygen concentration breathed by the rats decreased in a manner that was linear in hemoglobin saturation. These results do not support the existence of an arterial-venous gradient of HbNO under our experimental conditions.

  13. [The enhanced external counterpulsation as a method of non-invasive auxiliary blood circulation used for the combined rehabilitative treatment of the patients surviving after ischemic stroke (a review)].

    PubMed

    Eneeva, M A; Kostenko, E V; Razumov, A N; Petrova, L V; Bobyreva, S N; Nesuk, O M

    2015-01-01

    The present review of the foreign and domestic literature is concerned with the application of the method of enhanced external counterpulsation (EECP) therapy for the treatment of the patients presenting with various diseases. It is shown that many recent publications report extensive investigations of the clinical and neurophysiological aspects of the application of this method for the combined regenerative treatment of the patients surviving after ischemic stroke (IS). The possibility of the influence of EECP therapy on the system of regulation of the cerebral blood flow, the formation of collateral circulation in the ischemic tissue, and the cellular-humoral mechanisms are considered. It is concluded that the introduction of enhanced external counterpulsation therapy into the program of the combined rehabilitative treatment on an individual basis for the patients surviving after ischemic stroke is pathogenetically substantiated as promoting regression of clinical, neurological, and neuropsychological disorders.

  14. Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells

    PubMed Central

    Mairbäurl, Heimo

    2013-01-01

    During exercise the cardiovascular system has to warrant substrate supply to working muscle. The main function of red blood cells in exercise is the transport of O2 from the lungs to the tissues and the delivery of metabolically produced CO2 to the lungs for expiration. Hemoglobin also contributes to the blood's buffering capacity, and ATP and NO release from red blood cells contributes to vasodilation and improved blood flow to working muscle. These functions require adequate amounts of red blood cells in circulation. Trained athletes, particularly in endurance sports, have a decreased hematocrit, which is sometimes called “sports anemia.” This is not anemia in a clinical sense, because athletes have in fact an increased total mass of red blood cells and hemoglobin in circulation relative to sedentary individuals. The slight decrease in hematocrit by training is brought about by an increased plasma volume (PV). The mechanisms that increase total red blood cell mass by training are not understood fully. Despite stimulated erythropoiesis, exercise can decrease the red blood cell mass by intravascular hemolysis mainly of senescent red blood cells, which is caused by mechanical rupture when red blood cells pass through capillaries in contracting muscles, and by compression of red cells e.g., in foot soles during running or in hand palms in weightlifters. Together, these adjustments cause a decrease in the average age of the population of circulating red blood cells in trained athletes. These younger red cells are characterized by improved oxygen release and deformability, both of which also improve tissue oxygen supply during exercise. PMID:24273518

  15. Optoacoustic measurements of human placenta and umbilical blood oxygenation

    NASA Astrophysics Data System (ADS)

    Nanovskaya, T. N.; Petrov, I. Y.; Petrov, Y.; Patrikeeva, S. L.; Ahmed, M. S.; Hankins, G. D. V.; Prough, D. S.; Esenaliev, R. O.

    2016-03-01

    Adequate oxygenation is essential for normal embryogenesis and fetal growth. Perturbations in the intrauterine oxidative environment during pregnancy are associated with several pathophysiological disorders such as pregnancy loss, preeclampsia, and intrauterine growth restriction. We proposed to use optoacoustic technology for monitoring placental and fetal umbilical blood oxygenation. In this work, we studied optoacoustic monitoring of oxygenation in placenta and umbilical cord blood ex vivo using technique of placenta perfusion. We used a medical grade, nearinfrared, tunable, optoacoustic system developed and built for oxygenation monitoring in blood vessels and in tissues. First, we calibrated the system for cord blood oxygenation measurements by using a CO-Oximeter (gold standard). Then we performed validation in cord blood circulating through the catheters localized on the fetal side of an isolated placental lobule. Finally, the oxygenation measurements were performed in the perfused placental tissue. To increase or decrease blood oxygenation, we used infusion of a gas mixture of 95% O2 + 5% CO2 and 95% N2 + 5% CO2, respectively. In placental tissue, up to four cycles of changes in oxygenation were performed. The optoacoustically measured oxygenation in circulating cord blood and in placental lobule closely correlated with the actual oxygenation data measured by CO-Oximeter. We plan to further test the placental and cord blood oxygenation monitoring with optoacoustics in animal and clinical studies.

  16. Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease

    PubMed Central

    2010-01-01

    Background Tumor-related methylated DNA and circulating tumor cells (CTC) in the peripheral blood might be of prognostic importance in breast cancer. Thus, the aim of our study was to examine free methylated DNA and CTC in the blood from breast cancer patients and to correlate it with clinicopathological features known to influence prognosis. Materials and methods We prospectively obtained serum samples from 85 patients with breast cancer and 22 healthy volunteers. Sera were analysed by methylation specific PCR (MethyLight PCR) for five genes: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A), estrogen receptor 1 (ESR1), CDKN2A (p16) and glutathione s-transferase pi 1 (GSTP1). Beta actin (ACTB) served as control. In parallel matched peripheral blood of 63 patients was used to assay for circulating tumor cells in the peripheral blood by a modified immunomagnetic AdnaTest BreastCancerSelect with PCR detection for EPCAM, MUC1, MGB1 and SPDEF. Results We found a hypermethylation in the APC gene in 29% (25/85), in RASSF1A in 26% (22/85), in GSTP1 in 18% (14/76) and in ESR1 in 38% (32/85) of all breast cancer patients. No hypermethylation of CDKN2A was found (0/25). Blood samples of patients were defined CTC positive by detecting the EPCAM 13% (8/63), MUC1 16% (10/63), MGB 9% (5/55), SPDEF 12% (7/58) and in 27% detecting one or more genes (15/55). A significant difference was seen in methylated APC DNA between cancer patients and healthy volunteers. Moreover, methylated APC, RASSF1 and CTC were significantly different in metastatic versus non-metastatic disease. In addition, the presence of methylated APC, RASSF1A and CTC correlated significantly with AJCC-staging (p = 0.001, p = 0.031 and 0.002, respectively). High incidences of methylations were found for the genes RASSF1 and ESR1 in healthy individuals (both 23% 5/22). Methylated GSTP1 was predominantly found in the serum of patients with large primaries (p = 0.023) and was highly

  17. The Use of a New CellCollector to Isolate Circulating Tumor Cells from the Blood of Patients with Different Stages of Prostate Cancer and Clinical Outcomes - A Proof-of-Concept Study

    PubMed Central

    Theil, Gerit; Fischer, Kersten; Weber, Ekkehard; Medek, Rita; Hoda, Raschid; Lücke, Klaus; Fornara, Paolo

    2016-01-01

    Background and Methods Circulating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized. Forty-three PCa patients in different stages and 11 control subjects were studied. Some randomized samples were used to detect tumor-associated transcripts, such as prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA) and epidermal growth factor receptor (EGFR), in the isolated CTCs. Results The mean CTC counts were 4.6 CTCs [range, 0–8] in patients with localized PCa, 16.8 CTCs [range, 10–25] in patients with locally advanced PCa, and 26.8 CTCs [range, 0–98] in patients with metastatic PCa. The median follow-up time was 24 months, and there was a significant difference in the cancer-specific survival rates. Patients with CTC counts under 5 CTCs lived significantly longer (p = 0.035) than patients with more than 5 CTCs. We also demonstrated that the captured CTCs could be molecularly characterized. We detected tumor-associated transcripts of EGFR and PSMA in patients with metastatic PCa in 42.8% and 14.3% of the analyzed samples, respectively. Conclusion Our results indicate that the sensitive isolation and molecular characterization of CTCs can be achieved ex vivo using the wire. Patients with more than 5 CTCs had a mortality risk that was 7.0 times greater that of those with fewer than 5 CTCs (hazard ratio 7.0 95%, CI 1.1–29.39). This proof of concept was required for the approval of the use of

  18. Evidence for an amoeba-like infectious stage of Ichthyophonus sp. and description of a circulating blood stage: a probable mechanism for dispersal within the fish host.

    PubMed

    Kocan, Richard; LaPatra, Scott; Hershberger, Paul

    2013-04-01

    Small amoeboid cells, believed to be the infectious stage of Ichthyophonus sp., were observed in the bolus (stomach contents) and tunica propria (stomach wall) of Pacific staghorn sculpins and rainbow trout shortly after they ingested Ichthyophonus sp.-infected tissues. By 24-48 hr post-exposure (PE) the parasite morphed from the classically reported multinucleate thick walled schizonts to 2 distinct cell types, i.e., a larger multinucleate amoeboid cell surrounded by a narrow translucent zone and a smaller spherical cell surrounded by a "halo" and resembling a small schizont. Both cell types also appeared in the tunica propria, indicating that they had recently penetrated the columnar epithelium of the stomach. No Ichthyophonus sp. pseudo-hyphae ("germination tubes") were observed in the bolus or penetrating the stomach wall. Simultaneously, Ichthyophonus sp. was isolated in vitro from aortic blood, which was consistently positive from 6 to 144 hr PE, then only intermittently for the next 4 wk. Small PAS-positive cells observed in blood cultures grew into colonies consisting of non-septate tubules (pseudo-hyphae) terminating in multinucleated knob-like apices similar to those seen in organ explant cultures. Organ explants were culture positive every day; however, typical Ichthyophonus sp. schizonts were not observed histologically until 20-25 days PE. From 20 to 60 days PE, schizont diameter increased from ≤ 25 μm to ≥ 82 μm. Based on the data presented herein, we are confident that we have resolved the life cycle of Ichthyophonus sp. within the piscivorous host.

  19. Evidence for an amoeba-like infectious stage of ichthyophonus sp. and description of a circulating blood stage: a probable mechanism for dispersal within the fish host

    USGS Publications Warehouse

    Kocan, Richard; LaPatra, Scott; Hershberger, Paul

    2013-01-01

    Small amoeboid cells, believed to be the infectious stage of Ichthyophonus sp., were observed in the bolus (stomach contents) and tunica propria (stomach wall) of Pacific staghorn sculpins and rainbow trout shortly after they ingested Ichthyophonus sp.–infected tissues. By 24–48 hr post-exposure (PE) the parasite morphed from the classically reported multinucleate thick walled schizonts to 2 distinct cell types, i.e., a larger multinucleate amoeboid cell surrounded by a narrow translucent zone and a smaller spherical cell surrounded by a “halo” and resembling a small schizont. Both cell types also appeared in the tunica propria, indicating that they had recently penetrated the columnar epithelium of the stomach. No Ichthyophonus sp. pseudo-hyphae (“germination tubes”) were observed in the bolus or penetrating the stomach wall. Simultaneously, Ichthyophonus sp. was isolated in vitro from aortic blood, which was consistently positive from 6 to 144 hr PE, then only intermittently for the next 4 wk. Small PAS-positive cells observed in blood cultures grew into colonies consisting of non-septate tubules (pseudo-hyphae) terminating in multinucleated knob-like apices similar to those seen in organ explant cultures. Organ explants were culture positive every day; however, typical Ichthyophonus sp. schizonts were not observed histologically until 20–25 days PE. From 20 to 60 days PE, schizont diameter increased from ≤25 μm to ≥82 μm. Based on the data presented herein, we are confident that we have resolved the life cycle of Ichthyophonus sp. within the piscivorous host.

  20. Soluble recombinant CD69 receptors optimized to have an exceptional physical and chemical stability display prolonged circulation and remain intact in the blood of mice

    SciTech Connect

    Vaněk, Ondřej; Nálezková, Monika; Kavan, Daniel; Borovičková, Ivana; Pompach, Petr; Novák, Petr; Kumar, Vinay; Vannucci, Luca; Hudeček, Jiří; Hofbauerová, Kateřina; Kopecký, Jr., Vladimír; Brynda, Jiří; Kolenko, Petr; Dohnálek, Jan; Kadeřávek, Pavel; Chmelík, Josef; Gorčík, Lukáš; Žídek, Lukáš; Sklenář, Vladimír; Bezouška, Karel

    2009-08-14

    We investigated the soluble forms of the earliest activation antigen of human leukocyte CD69. This receptor is expressed at the cell surface as a type II homodimeric membrane protein. However, the elements necessary to prepare the soluble recombinant CD69 suitable for structural studies are a matter of controversy. We describe the physical, biochemical and in vivo characteristics of a highly stable soluble form of CD69 obtained by bacterial expression of an appropriate extracellular segment of this protein. Our construct has been derived from one used for CD69 crystallization by further optimization with regard to protein stability, solubility and easy crystallization under conditions promoting ligand binding. The resulting protein is stable at acidic pH and at temperatures of up to 65 C, as revealed by long-term stability tests and thermal denaturation experiments. Protein NMR and crystallography confirmed the expected protein fold, and revealed additional details of the protein characteristics in solution. The soluble CD69 refolded in a form of noncovalent dimers, as revealed by gel filtration, sedimentation velocity measurements, NMR and dynamic light scattering. The soluble CD69 proved to be remarkably stable in vivo when injected into the bloodstream of experimental mice. More than 70% of the most stable CD69 proteins is preserved intact in the blood 24 h after injection, whereas the less stable CD69 variants are rapidly taken up by the liver.

  1. A Subset of Circulating Blood Mycobacteria-Specific CD4 T Cells Can Predict the Time to Mycobacterium tuberculosis Sputum Culture Conversion

    PubMed Central

    Lugongolo, Masixole; Gwala, Thabisile; Kiravu, Agano; Deniso, Pamela; Stewart-Isherwood, Lynsey; Omar, Shaheed Vally; Grobusch, Martin P.; Coetzee, Gerrit; Conradie, Francesca; Ismail, Nazir; Kaplan, Gilla; Fallows, Dorothy

    2014-01-01

    We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR+Ki67+ on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67+HLA-DR+ Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67+HLA-DR+ T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ+IL2+TNFα+ CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67+HLA-DR+) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment. PMID:25048802

  2. Co-circulation of Plasmodium and Bacterial DNAs in Blood of Febrile and Afebrile Children from Urban and Rural Areas in Gabon.

    PubMed

    Mourembou, Gaël; Nzondo, Sydney Maghendji; Ndjoyi-Mbiguino, Angélique; Lekana-Douki, Jean Bernard; Kouna, Lady Charlène; Matsiegui, Pierre Blaise; Manego, Rella Zoleko; Moukandja, Irene Pegha; Keïta, Alpha Kabinet; Tissot-Dupont, Hervé; Fenollar, Florence; Raoult, Didier

    2016-07-01

    Malaria is considered to be the most common etiology of fever in sub-Saharan Africa while bacteremias exist but are under assessed. This study aimed to assess bacteremias and malaria in children from urban and rural areas in Gabon. DNA extracts from blood samples of 410 febrile and 60 afebrile children were analyzed using quantitative polymerase chain reaction. Plasmodium spp. was the microorganism most frequently detected in febrile (78.8%, 323/410) and afebrile (13.3%, 8/60) children, (P < 0.001). DNA from one or several bacteria were detected in 15 febrile patients (3.7%) but not in the controls (P = 0.1). This DNA was more frequently detected as co-infections among febrile children tested positive for Plasmodium (4.6%, 15/323) than in those tested negative for Plasmodium (0%, 0/87; P = 0.04). The bacteria detected were Streptococcus pneumoniae 2.4% (10/410), Staphylococcus aureus 1.7% (7/410), Salmonella spp. 0.7% (3/410), Streptococcus pyogenes 0.2% (1/410) and Tropheryma whipplei 0.2% (1/410) only in febrile children. Coxiella burnetii, Borrelia spp., Bartonella spp., Leptospira spp., and Mycobacterium tuberculosis were not observed. This paper reports the first detection of bacteremia related to T. whipplei in Gabon and shows that malaria decreases in urban areas but not in rural areas. Co-infections in febrile patients are common, highlighting the need to improve fever management strategies in Gabon. PMID:27114297

  3. A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion.

    PubMed

    Riou, Catherine; Gray, Clive M; Lugongolo, Masixole; Gwala, Thabisile; Kiravu, Agano; Deniso, Pamela; Stewart-Isherwood, Lynsey; Omar, Shaheed Vally; Grobusch, Martin P; Coetzee, Gerrit; Conradie, Francesca; Ismail, Nazir; Kaplan, Gilla; Fallows, Dorothy

    2014-01-01

    We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR+ Ki67+ on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67+ HLA-DR+ Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67+ HLA-DR+ T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ+ IL2+ TNFα+ CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67+ HLA-DR+) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment.

  4. A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion.

    PubMed

    Riou, Catherine; Gray, Clive M; Lugongolo, Masixole; Gwala, Thabisile; Kiravu, Agano; Deniso, Pamela; Stewart-Isherwood, Lynsey; Omar, Shaheed Vally; Grobusch, Martin P; Coetzee, Gerrit; Conradie, Francesca; Ismail, Nazir; Kaplan, Gilla; Fallows, Dorothy

    2014-01-01

    We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR+ Ki67+ on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67+ HLA-DR+ Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67+ HLA-DR+ T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ+ IL2+ TNFα+ CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67+ HLA-DR+) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment. PMID:25048802

  5. Adequate Selection of a Therapeutic Site Enables Efficient Development of Collateral Vessels in Angiogenic Treatment With Bone Marrow Mononuclear Cells

    PubMed Central

    Nemoto, Masaru; Koyama, Hiroyuki; Nishiyama, Ayako; Shigematsu, Kunihiro; Miyata, Tetsuro; Watanabe, Toshiaki

    2015-01-01

    Background Induction of angiogenic mechanisms to promote development of collateral vessels is considered promising for the treatment of peripheral arterial diseases. Collateral vessels generally develop from preexisting arteriolar connections, bypassing the diseased artery. We speculated that induction of angiogenic mechanisms should be directed to such arteriolar connections to achieve efficient collateral development. The aim of this study was to verify this hypothesis using autologous transplantation of bone marrow mononuclear cells in the rabbit model of chronic limb ischemia. Methods and Results The left femoral artery was excised to induce limb ischemia in male rabbits. In this model, arteriolar connections in the left coccygeofemoral muscle tend to develop into collateral vessels, although this transformation is insufficient to alleviate the limb ischemia. In contrast, arteriolar connections in the closely located adductor muscle do not readily develop into collateral vessels. At 21 days after ischemia initiation, a sufficient number of automononuclear cells were selectively injected in the left coccygeofemoral muscle (coccygeo group) or left adductor muscle (adductor group). Evaluation of calf blood pressure ratios, blood flow in the left internal iliac artery, and angiographic scores at day 28 after injection revealed that collateral development and improvement of limb ischemia were significantly more efficient in the coccygeo group than in the adductor group. Morphometric analysis of the coccygeofemoral muscle at day 14 showed similar results. Conclusions Specific delivery of mononuclear cells to the coccygeofemoral but not the adductor muscle effectively improves collateral circulation in the rabbit model of limb ischemia and suggests that adequate site selection can facilitate therapeutic angiogenesis. PMID:26370447

  6. Detection of circulating tumor cells.

    PubMed

    de Wit, Sanne; van Dalum, Guus; Terstappen, Leon W M M

    2014-01-01

    The increasing number of treatment options for patients with metastatic carcinomas has created an accompanying need for methods to determine if the tumor will be responsive to the intended therapy and to monitor its effectiveness. Ideally, these methods would be noninvasive and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells shed into the blood during metastasis may satisfy this need. Here we review the CellSearch technology used for the detection of circulating tumor cells and discuss potential future directions for improvements.

  7. Detection of Circulating Tumor Cells

    PubMed Central

    Terstappen, Leon W. M. M.

    2014-01-01

    The increasing number of treatment options for patients with metastatic carcinomas has created an accompanying need for methods to determine if the tumor will be responsive to the intended therapy and to monitor its effectiveness. Ideally, these methods would be noninvasive and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells shed into the blood during metastasis may satisfy this need. Here we review the CellSearch technology used for the detection of circulating tumor cells and discuss potential future directions for improvements. PMID:25133014

  8. Three sensitive assays do not provide evidence for circulating HuD-specific T cells in the blood of patients with paraneoplastic neurological syndromes with anti-Hu antibodies

    PubMed Central

    de Jongste, Adriaan H.C.; de Graaf, Marieke T.; Martinuzzi, Emanuela; van den Broek, Patricia D.M.; Kraan, Jaco; Lamers, Cor H.J.; Mallone, Roberto; Gratama, Jan W.; Sillevis Smitt, Peter A.E.

    2012-01-01

    Anti-Hu antibody–associated paraneoplastic neurological syndromes (Hu-PNSs) are severe and often precede the detection of a malignancy, usually small-cell lung cancer. In Hu-PNS, it is hypothesized that neuronal cells are destroyed by T cells targeted against HuD, a protein expressed by small-cell lung cancer cells and neurons. There is only limited evidence for the existence of HuD-specific T cells. To detect these T cells in the blood of Hu-PNS patients, we employed 3 highly sensitive assays that included T cell stimulation with dendritic cells (DCs) to specifically expand the number of any HuD-specific T cells. A total of 17 Hu-PNS patients were tested with 1 or more of the following 3 assays: (1) tetramer staining after stimulation of T cells with conventionally generated DCs (n = 9), (2) interleukin (IL)-13 enzyme-linked immunosorbent spot (ELISpot; n = 3), IL-4 and IL-5 and interferon (IFN)–γ multiplex cytokine bead array (n = 2) to assay cytokine production by T cells after stimulation with conventionally generated DCs, and (iii) IFN-γ ELISpot and tetramer staining after T cell stimulation with accelerated co-cultured DCs (n = 11). No circulating HuD-specific T cells were found. We suggest that either autoaggressive T cells in Hu-PNS are not targeted against HuD or that their numbers in the blood are too low for detection by highly sensitive techniques. PMID:22591661

  9. Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large-cell lymphoma.

    PubMed

    Damm-Welk, Christine; Busch, Kerstin; Burkhardt, Birgit; Schieferstein, Jutta; Viehmann, Susanne; Oschlies, Ilske; Klapper, Wolfram; Zimmermann, Martin; Harbott, Jochen; Reiter, Alfred; Woessmann, Willi

    2007-07-15

    Clinical and histopathological characteristics have limited prognostic value for children with anaplastic large-cell lymphoma (ALCL). We evaluated the presence, extent, and prognostic impact of circulating tumor cells in bone marrow (BM) and peripheral blood (PB) of children and adolescents with NPM-ALK-positive ALCL at diagnosis using qualitative and quantitative polymerase chain reaction (PCR) for NPM-ALK. Numbers of NPM-ALK transcripts were normalized to 10(4) copies ABL (NCNs). BM was analyzed from 80 patients and PB from 52. BM was positive for NPM-ALK in 47.5% of patients, and positivity was significantly correlated with clinical stage, mediastinal or visceral involvement, microscopic BM involvement, and histologic subtype. Qualitative and quantitative PCR results in BM and PB strongly correlated. BM PCR was associated with the cumulative incidence of relapses (CI-Rs): CI-R was 50% +/- 10% for 38 PCR-positive and 15% +/- 7% for 42 PCR-negative patients (P < .001). Sixteen patients with more than 10 NCNs NPM-ALK in BM had a CI-R of 71% +/- 14% compared with a CI-R of 18% +/- 6% for 59 patients with 10 or fewer NCNs (P < .001). PB PCR results led to a similar grouping. Thus, quantitative PCR in BM or PB allows identification of 20% of patients experiencing 60% of all relapses with an event-free survival of 20%.

  10. [Increase in skin blood circulation and transcutaneous oxygen partial pressure of the top of the foot in lower leg immersion in water containing carbon dioxide in patients with arterial occlusive disease. Results of a controlled study compared with fresh water].

    PubMed

    Hartmann, B; Drews, B; Burnus, C; Bassenge, E

    1991-01-01

    Semi-quantitative Doppler laser flowmetry and measurement of transcutaneous oxygen partial pressure (TCPO2 in mmHg) are reliable, non-invasive methods of continuous measurement suitable for underwater use. We measured the effect of aqueous CO2 (succinate + sodium bicarbonate = Kao Bub; 1400 mg CO2 per kg water) compared with fresh water (both at 34 degrees C, depth of leg immersion 35 cm, immersion time 20 min) on circulation and TCPO2 in the feet of 15 patients with bilateral stage-II occlusion of the Aa. fem. superf. intraindividually in a randomised, crossover trial. Measurements were made at the same time of day on two consecutive days. No change in either cutaneous microcirculation or TCPO2 was observed during immersion in fresh water. During immersion in a CO2 bath both culaneous blood flow (as expressed by Doppler laser flux) and the amplitude of the Doppler laser vasomotion flux increased more than threefold (p less than 0.001, Wilcoxon), while sitting TCPO2 increased by over 10% (from 63 to 71 mmHg; p less than 0.001). The observed changes in oxygen dissociation and cutaneous microcirculation may help to provide an explanation for the well-known therapeutic effect of CO2 baths in all stages of occlusive arterial disease. PMID:1776351

  11. Circulating tumor cells in blood of primary breast cancer patients assessed by a novel RT-PCR test kit and comparison with status of bone marrow-disseminated tumor cells.

    PubMed

    Schmitt, Manfred; Foekens, John A

    2009-01-01

    In breast cancer, circulating tumor cells (CTCs)/disseminated tumor cells (DTCs) may serve as independent adverse prognostic variables, to monitor the course of the disease and to predict response or failure to cancer therapy. Most of the techniques to enumerate DTCs in the bone marrow or CTCs in the bloodstream of breast cancer patients rely on a combination of an enrichment step and a detection step. A novel RT-PCR method, the AdnaTest BreastCancer kit, was developed for the enrichment of CTCs from peripheral blood of breast cancer patients followed by identification of CTC-associated marker transcripts by reverse transcription and PCR. Although this test has been demonstrated to identify breast cancer patients at risk, standardization of this technique and direct comparison with other established breast cancer CTC enrichment and detection techniques is still lacking, but highly needed. This is done best within prospective clinical trials, such as in the ongoing DETECT, SUCCESS, and BR-01-2004 trials.

  12. The Pulmonary Circulation and Exercise Responses in the Elderly

    PubMed Central

    Taylor, Bryan J.; Johnson, Bruce D.

    2014-01-01

    Aging is associated with a progressive deterioration in the structure and function of the pulmonary circulation. Remodeling of the pulmonary vasculature occurs from maturity to senescence that is characterized by an increase in pulmonary vascular stiffness, pulmonary vascular pressures, and pulmonary vascular resistance along with increased heterogeneity of alveolar ventilation and pulmonary perfusion and decreased pulmonary capillary blood volume and membrane diffusing capacity that is consistent with a reduction in alveolar-capillary surface area. In theory, the aforementioned age-related changes in the pulmonary circulation may conspire to make elderly individuals more susceptible to gas exchange abnormalities during exercise. However, despite the erosion in ventilatory reserve with aging, the healthy older adult appears able to maintain alveolar ventilation at a level that allows maintenance of arterial blood gases within normal limits, even during heavy exercise. This ability to maintain adequate gas exchange likely occurs because age-related reductions in the maximal metabolic demand of exercise occur at a rate equal to or greater than the rate of deterioration in ventilatory reserve. A more prominent aspect of aging is the loss of lung elastic recoil that is associated with a modest reduction in the expiratory boundary of the maximal flow-volume envelope. This in turn increases the severity of expiratory airflow limitation and induces dynamic lung hyperinflation during exercise. The consequences of this age-associated decrease in elastic recoil on the pulmonary circulation are speculative, but an age-associated decline in elastic recoil may influence pulmonary vascular resistance and cardiac output, in addition to its impact on the work and oxygen cost of breathing. PMID:20941654

  13. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  14. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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  15. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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  16. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  17. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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  18. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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  19. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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  20. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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  1. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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  2. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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  3. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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  4. 40 CFR 716.25 - Adequate file search.

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  5. 40 CFR 716.25 - Adequate file search.

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    2014-07-01

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  6. 40 CFR 716.25 - Adequate file search.

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    2012-07-01

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  7. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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  8. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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  9. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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  10. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 2 2011-07-01 2011-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  11. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  12. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  13. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  14. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  15. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  16. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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  17. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  18. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  19. 7 CFR 4290.200 - Adequate capital for RBICs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Adequate capital for RBICs. 4290.200 Section 4290.200 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND... Qualifications for the RBIC Program Capitalizing A Rbic § 4290.200 Adequate capital for RBICs. You must meet...

  20. "Something Adequate"? In Memoriam Seamus Heaney, Sister Quinlan, Nirbhaya

    ERIC Educational Resources Information Center

    Parker, Jan

    2014-01-01

    Seamus Heaney talked of poetry's responsibility to represent the "bloody miracle", the "terrible beauty" of atrocity; to create "something adequate". This article asks, what is adequate to the burning and eating of a nun and the murderous gang rape and evisceration of a medical student? It considers Njabulo…

  1. Anatomy of diaphragmatic circulation.

    PubMed

    Comtois, A; Gorczyca, W; Grassino, A

    1987-01-01

    The diaphragmatic circulation was studied in 48 mongrel dogs weighing 10-35 kg by injecting acrylic coloring into the arteries and veins of the diaphragm. The phrenic arteries and internal mammary arteries were found to anastomose head to head, forming an internal arterial circle around the medial leaflet of the diaphragm tendon. This arterial circle emitted vascular branches that traveled between muscle fibers toward the periphery of the diaphragm. These branches anastomosed with vessels of the intercostal arteries to form costophrenic arcades all along the fibers of the crural and costal diaphragms. The intercostal arteries were anastomosed to one another by small vessels within the muscular diaphragm, thus forming an arterial ring around the insertions of the diaphragm on the ribs. The venous drainage has an anatomic distribution similar to that observed on the arterial side, but with the additional presence of valves that could play a role in directing blood flow.

  2. Thrombography reveals thrombin generation potential continues to deteriorate following cardiopulmonary bypass surgery despite adequate hemostasis.

    PubMed

    Wong, Raymond K; Sleep, Joseph R; Visner, Allison J; Raasch, David J; Lanza, Louis A; DeValeria, Patrick A; Torloni, Antonio S; Arabia, Francisco A

    2011-03-01

    The intrinsic and extrinsic activation pathways of the hemostatic system converge when prothrombin is converted to thrombin. The ability to generate an adequate thrombin burst is the most central aspect of the coagulation cascade. The thrombin-generating potential in patients following cardiopulmonary bypass (CPB) may be indicative of their hemostatic status. In this report, thrombography, a unique technique for directly measuring the potential of patients' blood samples to generate adequate thrombin bursts, is used to characterize the coagulopathic profile in post-CPB patients. Post-CPB hemostasis is typically achieved with protamine reversal of heparin anticoagulation and occasionally supplemented with blood product component transfusions. In this pilot study, platelet poor plasma samples were derived from 11 primary cardiac surgery patients at five time points: prior to CPB, immediately post-protamine, upon arrival to the intensive care unit (ICU), 3 hours post-ICU admission, and 24 hours after ICU arrival. Thrombography revealed that the Endogenous Thrombin Potential (ETP) was not different between [Baseline] and [PostProtamine] but proceeded to deteriorate in the immediate postoperative period. At the [3HourPostICU] time point, the ETP was significantly lower than the [Baseline] values, 1233 +/- 591 versus 595 +/- 379 nM.min (mean +/- SD; n=9, p < .005), despite continued adequacy of hemostasis. ETPs returned to baseline values the day after surgery. Transfusions received, conventional blood coagulation testing results, and blood loss volumes are also presented. Despite adequate hemostasis, thrombography reveals an underlying coagulopathic process that could put some cardiac surgical patients at risk for postoperative bleeding. Thrombography is a novel technique that could be developed into a useful tool for perfusionists and physicians to identify coagulopathies and optimize blood management following CPB. PMID:21449230

  3. Polyion complex micelle MRI contrast agents from poly(ethylene glycol)-b-poly(l-lysine) block copolymers having Gd-DOTA; preparations and their control of T(1)-relaxivities and blood circulation characteristics.

    PubMed

    Shiraishi, Kouichi; Kawano, Kumi; Maitani, Yoshie; Yokoyama, Masayuki

    2010-12-01

    The current study synthesized macromolecular magnetic resonance imaging (MRI) contrast agents constituted of the poly(ethylene glycol)-b-poly(L-lysine) block copolymer (PEG-P(Lys)). A chelate group, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), was attached to the primary amino group of the block copolymer in desired contents. Gd-DOTA-based macromolecular contrast agents were prepared from PEG-P(Lys) having DOTA (PEG-P(Lys-DOTA) and Gd(III) ions. All of the PEG-P(Lys) block copolymers having gadolinium ions (PEG-P(Lys-DOTA-Gd)) showed higher T(1) relaxivity (per gadolinium), r(1)=5.6-7.3mM(-1)s(-1), than that of a low-molecular-weight gadolinium-chelate, diethylenetriaminepentaacetic acid-gadolinium(III) (Gd-DTPA) at 9.4T. The study prepared the polyion complex (PIC) micelles from the amino groups of the lysine units and an oppositely charged polyanion, poly(methacrylic acid) or dextran sulfate, in an aqueous medium. In contrast, the fully DOTA-attached PEG-P(Lys-DOTA-Gd) formed a PIC with a polycation. Compared with partially DOTA-attached cationic PEG-P(Lys-DOTA-Gd), this PIC micelle yielded a forty percent decrease of r(1). This r(1) decrease was considered to result from a change in the accessibility of water molecules to gadolinium ions in the micelles' inner core. The r(1) was decreased upon formation of the PIC micelle, and this change proved that our concept worked in vitro. Blood-circulation characteristics of PIC micelles were controlled by means of changing the molecular weight of the counter anion. The PIC micelles accumulated in tumor tissues, and MRI study showed T1W image of axial slice of tumor area was significantly enhanced at 24h after the injection.

  4. A brief etymology of the collateral circulation.

    PubMed

    Faber, James E; Chilian, William M; Deindl, Elisabeth; van Royen, Niels; Simons, Michael

    2014-09-01

    It is well known that the protective capacity of the collateral circulation falls short in many individuals with ischemic disease of the heart, brain, and lower extremities. In the past 15 years, opportunities created by molecular and genetic tools, together with disappointing outcomes in many angiogenic trials, have led to a significant increase in the number of studies that focus on: understanding the basic biology of the collateral circulation; identifying the mechanisms that limit the collateral circulation's capacity in many individuals; devising methods to measure collateral extent, which has been found to vary widely among individuals; and developing treatments to increase collateral blood flow in obstructive disease. Unfortunately, accompanying this increase in reports has been a proliferation of vague terms used to describe the disposition and behavior of this unique circulation, as well as the increasing misuse of well-ensconced ones by new (and old) students of collateral circulation. With this in mind, we provide a brief glossary of readily understandable terms to denote the formation, adaptive growth, and maladaptive rarefaction of collateral circulation. We also propose terminology for several newly discovered processes that occur in the collateral circulation. Finally, we include terms used to describe vessels that are sometimes confused with collaterals, as well as terms describing processes active in the general arterial-venous circulation when ischemic conditions engage the collateral circulation. We hope this brief review will help unify the terminology used in collateral research.

  5. Understanding Your Adequate Yearly Progress (AYP), 2011-2012

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2011

    2011-01-01

    The "No Child Left Behind Act (NCLB) of 2001" requires all schools, districts/local education agencies (LEAs) and states to show that students are making Adequate Yearly Progress (AYP). NCLB requires states to establish targets in the following ways: (1) Annual Proficiency Target; (2) Attendance/Graduation Rates; and (3) Participation Rates.…

  6. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  7. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  8. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  9. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  10. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  11. Adequate Schools and Inadequate Education: An Anthropological Perspective.

    ERIC Educational Resources Information Center

    Wolcott, Harry F.

    To illustrate his claim that schools generally do a remarkably good job of schooling while the society makes inadequate use of other means to educate young people, the author presents a case history of a young American (identified pseudonymously as "Brad") whose schooling was adequate but whose education was not. Brad, jobless and homeless,…

  12. Comparability and Reliability Considerations of Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Maier, Kimberly S.; Maiti, Tapabrata; Dass, Sarat C.; Lim, Chae Young

    2012-01-01

    The purpose of this study is to develop an estimate of Adequate Yearly Progress (AYP) that will allow for reliable and valid comparisons among student subgroups, schools, and districts. A shrinkage-type estimator of AYP using the Bayesian framework is described. Using simulated data, the performance of the Bayes estimator will be compared to…

  13. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... operate actively in accordance with your Articles and within the context of your business plan,...

  14. Assessing Juvenile Sex Offenders to Determine Adequate Levels of Supervision.

    ERIC Educational Resources Information Center

    Gerdes, Karen E.; And Others

    1995-01-01

    This study analyzed the internal consistency of four inventories used by Utah probation officers to determine adequate and efficacious supervision levels and placement for juvenile sex offenders. Three factors accounted for 41.2 percent of variance (custodian's and juvenile's attitude toward intervention, offense characteristics, and historical…

  15. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... identifiable personal data and automated systems shall be adequately trained in the security and privacy of... records in which identifiable personal data are processed or maintained, including all reports and output... personal records or data; must minimize, to the extent practicable, the risk that skilled technicians...

  16. Do Beginning Teachers Receive Adequate Support from Their Headteachers?

    ERIC Educational Resources Information Center

    Menon, Maria Eliophotou

    2012-01-01

    The article examines the problems faced by beginning teachers in Cyprus and the extent to which headteachers are considered to provide adequate guidance and support to them. Data were collected through interviews with 25 school teachers in Cyprus, who had recently entered teaching (within 1-5 years) in public primary schools. According to the…

  17. Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat cancer.

    PubMed

    Bellassai, Noemi; Spoto, Giuseppe

    2016-10-01

    The detection of cancer biomarkers freely circulating in blood offers new opportunities for cancer early diagnosis, patient follow-up, and therapy efficacy assessment based on liquid biopsy. In particular, circulating cell-free nucleic acids released from tumor cells have recently attracted great attention also because they become detectable in blood before the appearance of other circulating biomarkers, such as circulating tumor cells. The detection of circulating nucleic acids poses several technical challenges that arise from their low concentration and relatively small size. Here, possibilities offered by innovative biosensing approaches for the detection of circulating DNA in peripheral blood and blood-derived products such as plasma and serum blood are discussed. Different transduction principles are used to detect circulating DNAs and great advantages are derived from the combined use of nanostructured materials.

  18. Virtual extracorporeal circulation process.

    PubMed

    Boschetti, F; Montevecchi, F M; Fumero, R

    1997-06-01

    Virtual instruments for an extracorporeal circulation (ECC) process were developed to simulate the reactions of a patient to different artificial perfusion conditions. The computer simulation of the patient takes into account the hydraulic, volume, thermal and biochemical phenomena and their interaction with the devices involved in ECC (cannulae dimensions, oxygenator and filter types, pulsatile or continuous pump and thermal exchangers). On the basis of the patient's initialisation data (height, weight, Ht) and perfusion variables (pump flow rate, water temperature, gas flow rate and composition) imposed by the operator, the virtual ECC monitors simulated arterial and venous pressure tracings in real time, along with arterial and venous flow rate tracings, urine production tracing and temperature levels. Oxyhemoglobin arterial and venous blood saturation together with other related variables (pO2, pCO2, pH, HCO3 are also monitored. A drug model which allows the simulation of the effect of vasodilator and diuretic drugs is also implemented. Alarms are provided in order to check which variables (pressure, saturation, pH, urine flow) are out of the expected ranges during the ECC simulation. Consequently the possibility of modifying the control parameters of the virtual devices of the ECC in run-time mode offers an interaction mode between the operator and the virtual environment. PMID:9259211

  19. Plants and Photosynthesis: Level III, Unit 3, Lesson 1; The Human Digestive System: Lesson 2; Functions of the Blood: Lesson 3; Human Circulation and Respiration: Lesson 4; Reproduction of a Single Cell: Lesson 5; Reproduction by Male and Female Cells: Lesson 6; The Human Reproductive System: Lesson 7; Genetics and Heredity: Lesson 8; The Nervous System: Lesson 9; The Glandular System: Lesson 10. Advanced General Education Program. A High School Self-Study Program.

    ERIC Educational Resources Information Center

    Manpower Administration (DOL), Washington, DC. Job Corps.

    This self-study program for the high-school level contains lessons in the following subjects: Plants and Photosynthesis; The Human Digestive System; Functions of the Blood; Human Circulation and Respiration; Reproduction of a Single Cell; Reproduction by Male and Female Cells; The Human Reproductive System; Genetics and Heredity; The Nervous…

  20. A new look at cerebrospinal fluid circulation

    PubMed Central

    2014-01-01

    According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation. PMID:24817998

  1. [Circulating tumor cells in head and neck cancer].

    PubMed

    Guntinas-Lichius, O; Pachmann, K

    2015-06-01

    Circulating tumor cells are defined as tumor cells which are circulating in the peripheral blood of the cancer patient. While several large studies have investigated the role of circulating tumor cells in other solid tumors, the importance of these tumor cells in patients with head and neck cancer was turned into the focus not until the recent years. In other solid tumor the presence of circulating tumor cells often seems to be a negative prognostic marker and seems to be a marker for therapy response. The present article wants to give an overview about the knowledge on circulating tumor cells and their clinical relevance in head and neck cancer. The methodology to detect circulating tumor cells will be critically reflected. The future potential of the detection of circulating tumor cells in head and neck cancer patients will be discussed.

  2. Apparatus Circulates Sterilizing Gas

    NASA Technical Reports Server (NTRS)

    Cross, John H.; Schwarz, Ray P.

    1991-01-01

    Apparatus circulates sterilizing gas containing ethylene oxide and chlorofluorocarbon through laboratory or medical equipment. Confines sterilizing gas, circulating it only through parts to be treated. Consists of two units. One delivers ethylene oxide/chlorofluorocarbon gas mixture and removes gas after treatment. Other warms, humidifies, and circulates gas through equipment to be treated. Process provides reliable sterilization with negligible residual toxicity from ethylene oxide. Particularly suitable for sterilization of interiors of bioreactors, heart/lung machines, dialyzers, or other equipment including complicated tubing.

  3. [Abdominal cure procedures. Adequate use of Nobecutan Spray].

    PubMed

    López Soto, Rosa María

    2009-12-01

    Open abdominal wounds, complicated by infection and/or risk of eventration tend to become chronic and usually require frequent prolonged cure. Habitual changing of bandages develop into one of the clearest risk factors leading to the deterioration of perilesional cutaneous integrity. This brings with it new complications which draw out the evolution of the process, provoking an important deterioration in quality of life for the person who suffers this and a considerable increase in health costs. What is needed is a product and a procedure which control the risk of irritation, which protect the skin, which favor a patient's comfort and which shorten treatment requirements while lowering health care expenses. This report invites medical personnel to think seriously about the scientific rationale, and treatment practice, as to why and how to apply Nobecutan adequately, this reports concludes stating the benefits in the adequate use of this product. The objective of this report is to guarantee the adequate use of this product in treatment of complicated abdominal wounds. This product responds to the needs which are present in these clinical cases favoring skin care apt isolation and protection, while at the same time, facilitating the placement and stability of dressings and bandages used to cure wounds. In order for this to happen, the correct use of this product is essential; medical personnel must pay attention to precautions and recommendations for proper application. The author's experiences in habitual handling of this product during various years, included in the procedures for standardized cures for these wounds, corroborates its usefulness; the author considers use of this product to be highly effective while being simple to apply; furthermore, one succeeds in providing quality care and optimizes resources employed.

  4. Blood circulating microparticle species in relapsing–remitting and secondary progressive multiple sclerosis. A case–control, cross sectional study with conventional MRI and advanced iron content imaging outcomes

    PubMed Central

    Alexander, J.S.; Chervenak, R.; Weinstock-Guttman, B.; Tsunoda, I.; Ramanathan, M.; Martinez, N.E.; Omura, S.; Sato, F.; Chaitanya, G.V.; Minagar, A.; McGee, J.; Jennings, M.H.; Monceaux, C.; Becker, F.; Cvek, U.; Trutschl, M.; Zivadinov, R.

    2015-01-01

    Background Although multiple sclerosis (MS) is thought to represent an excessive and inappropriate immune response to several central nervous system (CNS) autoantigens, increasing evidence also suggests that MS may also be a neurovascular inflammatory disease, characterized by endothelial activation and shedding of cell membrane microdomains known as ‘microparticles’ into the circulation. Objective To investigate the relationships between these endothelial biomarkers and MS. Methods We examined the relative abundance of CD31+/PECAM-1, CD51+CD61+ (αV–β3) and CD54+ (ICAM-1) bearing microparticles in sera of healthy individuals, patients with relapsing–remitting MS, and secondary-progressive MS. We also investigated the correlation among circulating levels of different microparticle species in MS with conventional MRI (T2- and T1-lesion volumes and brain atrophy), as well as novel MR modalities [assessment of iron content on susceptibility-weighted imaging (SWI)-filtered phase]. Results Differences in circulating microparticle levels were found among MS groups, and several microparticle species (CD31+/CD51+/CD61+/CD54+) were found to correlate with conventional MRI and SWI features of MS. Conclusion These results indicate that circulating microparticles’ profiles in MS may support mechanistic roles for microvascular stress and injury which is an underlying contributor not only to MS initiation and progression, but also to pro-inflammatory responses. PMID:26073484

  5. Intestinal circulation during inhalation anesthesia

    SciTech Connect

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-04-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  6. Influence of simulated microgravity on clock genes expression rhythmicity and underlying blood circulating miRNAs-mRNA co-expression regulatory mechanism in C57BL/6J mice

    NASA Astrophysics Data System (ADS)

    Lv, Ke; Qu, Lina

    Purpose: It is vital for astronauts to maintain the optimal alertness and neurobehavioral function. Among various factors that exist in the space flight and long-duration mission environment, gravity changes may probably an essential environmental factor to interfere with internal circadian rhythms homeostasis and sleep quality, but the underlying mechanism is unclear. Mammals' biological clock is controlled by the suprachiasmatic nucleus (SCN), and peripheral organs adjust their own rhythmicity with the central signals. Nevertheless,the mechanism underlying this synchronizition process is still unknown. microRNAs (miRNAs) are about 19~22nt long regulatory RNAs that serve as critical modulators of post-transcriptional gene regulation. Recently, circulating miRNAs were found to have the regulatory role between cells and peripheral tissues, besides its function inside the cells. This study aims to investigate the regulatory signal transduction role of miRNAs between SCN and peripheral biological clock effecter tissues and to further decipher the mechanism of circadian disturbance under microgravity. Method: Firstly, based on the assumption that severe alterations in the expression of genes known to be involved in circadian rhythms may affect the expression of other genes, the labeled cDNA from liver and suprachiasmatic nucleus (SCN) of clock-knockout mice and control mice in different time points were cohybridized to microarrays. The fold change exceeding 2 (FC>2) was used to identify genes with altered expression levels in the knockout mice compared with control mice. Secondly, male C57BL/6J mice at 8 weeks of age were individually caged and acclimatized to the laboratory conditions (12h light/dark cycle) before being used for continuous core body temperature and activity monitoring. The mice were individually caged and tail suspended using a strip of adhesive surgical tape attached to a chain hanging from a pulley. Peripheral blood and liver tissues collection

  7. Cognitive problems related to vertebrobasilar circulation.

    PubMed

    Koçer, Abdulkadir

    2015-01-01

    Neurodegenerative disorders are characterized by decreased regional cerebral blood flow. Supporting this concept, both cognitive training exercises and physical activity promote blood flow increase and correlate with healthy cognitive aging. The terminal branches of the posterior circulation supply blood to areas of the brain, such as the thalamus, hippocampus, occipital lobe, and cerebellum, involved with important intellectual functions, particularly recent memory, visual-spatial functioning, and visuomotor adaptations. Amnesia and visual agnosia may be a complication of not only posterior circulation infarctions but also vertebrobasilar insufficiency (VBI) without accompanying structural infarcts. The cognitive impairment maybe a manifestation of transient attacks and may persist beyond resolution of symptoms related to ischemia. Early recognition of cognitive deficits in the VBI patient is important because several recent reports show stent placements or medical treatment may improve cognition. PMID:26738337

  8. Quantifying dose to the reconstructed breast: Can we adequately treat?

    SciTech Connect

    Chung, Eugene; Marsh, Robin B.; Griffith, Kent A.; Moran, Jean M.; Pierce, Lori J.

    2013-04-01

    To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V{sub 20}. Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.

  9. Tissue blood flow mapping

    NASA Astrophysics Data System (ADS)

    Nilsson, G. E.

    1997-01-01

    The operating principles of Laser Doppler Perfusion Imaging (LDPI) for visualization of the tissue blood perfusion are explained. Using this emerging technology skin perfusion has been investigated in healthy volunteers and in patients with various conditions that affect skin blood flow. LDPI is anticipated to be particularly useful in evaluation of peripheral circulation in diabetics, as an objective tool in irritancy patch testing, assessment of burnt skin and visualization of spot-wise hyperperfusion in breast skin in association with carcinoma.

  10. In vivo acoustic and photoacoustic focusing of circulating cells

    NASA Astrophysics Data System (ADS)

    Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.

    2016-03-01

    In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models.

  11. In vivo acoustic and photoacoustic focusing of circulating cells

    PubMed Central

    Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.

    2016-01-01

    In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models. PMID:26979811

  12. Choices for achieving adequate dietary calcium with a vegetarian diet.

    PubMed

    Weaver, C M; Proulx, W R; Heaney, R

    1999-09-01

    To achieve adequate dietary calcium intake, several choices are available that accommodate a variety of lifestyles and tastes. Liberal consumption of dairy products in the diet is the approach of most Americans. Some plants provide absorbable calcium, but the quantity of vegetables required to reach sufficient calcium intake make an exclusively plant-based diet impractical for most individuals unless fortified foods or supplements are included. Also, dietary constituents that decrease calcium retention, such as salt, protein, and caffeine, can be high in the vegetarian diet. Although it is possible to obtain calcium balance from a plant-based diet in a Western lifestyle, it may be more convenient to achieve calcium balance by increasing calcium consumption than by limiting other dietary factors.

  13. Genetic Modification of Preimplantation Embryos: Toward Adequate Human Research Policies

    PubMed Central

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo modification proposals might not receive adequate scientific and ethical scrutiny. This article describes current policy shortcomings and recommends policy actions designed to ensure that the investigational genetic modification of embryos meets accepted standards for research on human subjects. PMID:15016248

  14. [Clinical study on total intravenous anesthesia with droperidol, fentanyl, and ketamine--18. Effect on peripheral circulation as judged by core-peripheral temperature gradient].

    PubMed

    Ohkawa, H; Iwakawa, T; Ohtomo, N; Kitayama, M; Miyahara, A; Matsuki, A

    1993-04-01

    Effect of total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK) on peripheral circulation was studied by examining core-peripheral temperature gradient in twenty five patients who underwent abdominal surgery. A core temperature probe was attached on the forehead and peripheral probe on the palm of the hand of the side on which the blood pressure cuff was not applied. The temperature gradient was less than three degrees centigrade in 60% of the patients and the gradient was significantly less as compared with that of isoflurane anesthesia even at 300 minutes after the start of surgical operation. This advantage would have been caused by such factors as circulatory stimulating effect of ketamine, sympathetic blocking effect by droperidol and adequate postoperative analgesia by fentanyl and norketamine, a metabolite of ketamine. The results suggest that DFK would exert a beneficial effect on peripheral circulation, particularly during prolonged surgical procedures.

  15. Oxygen delivery: the principal role of the circulation.

    PubMed

    Wolff, Christopher B

    2013-01-01

    Autoregulation of blood flow to most individual organs is well known. The balance of oxygen supply relative to the rate of oxygen consumption ensures normal function. There is less reserve as regards oxygen supply than for any other necessary metabolite or waste product so oxygen supply is flow dependent. Reduced rate of supply compromises tissue oxygenation long before any other substance. The present report reiterates evidence from earlier studies demonstrating that the rate of oxygen delivery (DO2), for most individual tissues, is well sustained at a value bearing a ratio to oxygen consumption (VO2) which is specific for the organ concerned. For the brain DO2 is sustained at approximately three times the rate of oxygen consumption and for exercising skeletal muscle (below the anaerobic threshold), a ratio close to 1.5. The tissue-specific ratios are sustained in the face of alterations in local VO2 and lowered arterial oxygen content (CaO2). Tolerance varies between different organs. Hence, the role of the circulation is predominantly one of ensuring an adequate supply of oxygen. The precise values of the individual tissue DO2:VO2 ratios apply within physiological ranges which require further investigation. PMID:23852474

  16. Mountains and Tropical Circulation

    NASA Astrophysics Data System (ADS)

    Naiman, Z.; Goodman, P. J.; Krasting, J. P.; Malyshev, S.; Russell, J. L.; Stouffer, R. J.

    2015-12-01

    Observed tropical convection exhibits zonal asymmetries that strongly influence spatial precipitation patterns. The drivers of changes to this zonally-asymmetric Walker circulation on decadal and longer timescales have been the focus of significant recent research. Here we use two state-of-the-art earth system models to explore the impact of earth's mountains on the Walker circulation. When all land-surface topography is removed, the Walker circulation weakens by 33-59%. There is a ~30% decrease in global, large-scale upward vertical wind velocities in the middle of the troposphere, but only minor changes in global average convective mass flux, precipitation, surface and sea-surface temperatures. The zonally symmetric Hadley circulation is also largely unchanged. Following the spatial pattern of changes to large-scale vertical wind velocities, precipitation becomes less focused over the tropics. The weakening of the Walker circulation, but not the Hadley circulation, is similar to the behavior of climate models during radiative forcing experiments: in our simulations, the weakening is associated with changes in vertical wind velocities, rather than the hydrologic cycle. These results indicate suggest that mountain heights may significantly influence the Walker circulation on geologic time scales, and observed changes in tropical precipitation over millions of years may have been forced by changes in tropical orography.

  17. Using the Gamma-Poisson Model to Predict Library Circulations.

    ERIC Educational Resources Information Center

    Burrell, Quentin L.

    1990-01-01

    Argues that the gamma mixture of Poisson processes, for all its perceived defects, can be used to make predictions regarding future library book circulations of a quality adequate for general management requirements. The use of the model is extensively illustrated with data from two academic libraries. (Nine references) (CLB)

  18. Adequate Iodine Status in New Zealand School Children Post-Fortification of Bread with Iodised Salt.

    PubMed

    Jones, Emma; McLean, Rachael; Davies, Briar; Hawkins, Rochelle; Meiklejohn, Eva; Ma, Zheng Feei; Skeaff, Sheila

    2016-01-01

    Iodine deficiency re-emerged in New Zealand in the 1990s, prompting the mandatory fortification of bread with iodised salt from 2009. This study aimed to determine the iodine status of New Zealand children when the fortification of bread was well established. A cross-sectional survey of children aged 8-10 years was conducted in the cities of Auckland and Christchurch, New Zealand, from March to May 2015. Children provided a spot urine sample for the determination of urinary iodine concentration (UIC), a fingerpick blood sample for Thyroglobulin (Tg) concentration, and completed a questionnaire ascertaining socio-demographic information that also included an iodine-specific food frequency questionnaire (FFQ). The FFQ was used to estimate iodine intake from all main food sources including bread and iodised salt. The median UIC for all children (n = 415) was 116 μg/L (females 106 μg/L, males 131 μg/L) indicative of adequate iodine status according to the World Health Organisation (WHO, i.e., median UIC of 100-199 μg/L). The median Tg concentration was 8.7 μg/L, which was <10 μg/L confirming adequate iodine status. There was a significant difference in UIC by sex (p = 0.001) and ethnicity (p = 0.006). The mean iodine intake from the food-only model was 65 μg/day. Bread contributed 51% of total iodine intake in the food-only model, providing a mean iodine intake of 35 μg/day. The mean iodine intake from the food-plus-iodised salt model was 101 μg/day. In conclusion, the results of this study confirm that the iodine status in New Zealand school children is now adequate. PMID:27196925

  19. Adequate Iodine Status in New Zealand School Children Post-Fortification of Bread with Iodised Salt

    PubMed Central

    Jones, Emma; McLean, Rachael; Davies, Briar; Hawkins, Rochelle; Meiklejohn, Eva; Ma, Zheng Feei; Skeaff, Sheila

    2016-01-01

    Iodine deficiency re-emerged in New Zealand in the 1990s, prompting the mandatory fortification of bread with iodised salt from 2009. This study aimed to determine the iodine status of New Zealand children when the fortification of bread was well established. A cross-sectional survey of children aged 8–10 years was conducted in the cities of Auckland and Christchurch, New Zealand, from March to May 2015. Children provided a spot urine sample for the determination of urinary iodine concentration (UIC), a fingerpick blood sample for Thyroglobulin (Tg) concentration, and completed a questionnaire ascertaining socio-demographic information that also included an iodine-specific food frequency questionnaire (FFQ). The FFQ was used to estimate iodine intake from all main food sources including bread and iodised salt. The median UIC for all children (n = 415) was 116 μg/L (females 106 μg/L, males 131 μg/L) indicative of adequate iodine status according to the World Health Organisation (WHO, i.e., median UIC of 100–199 μg/L). The median Tg concentration was 8.7 μg/L, which was <10 μg/L confirming adequate iodine status. There was a significant difference in UIC by sex (p = 0.001) and ethnicity (p = 0.006). The mean iodine intake from the food-only model was 65 μg/day. Bread contributed 51% of total iodine intake in the food-only model, providing a mean iodine intake of 35 μg/day. The mean iodine intake from the food-plus-iodised salt model was 101 μg/day. In conclusion, the results of this study confirm that the iodine status in New Zealand school children is now adequate. PMID:27196925

  20. Dose Limits for Man do not Adequately Protect the Ecosystem

    SciTech Connect

    Higley, Kathryn A.; Alexakhin, Rudolf M.; McDonald, Joseph C.

    2004-08-01

    It has been known for quite some time that different organisms display differing degrees of sensitivity to the effects of ionizing radiations. Some microorganisms such as the bacterium Micrococcus radiodurans, along with many species of invertebrates, are extremely radio-resistant. Humans might be categorized as being relatively sensitive to radiation, and are a bit more resistant than some pine trees. Therefore, it could be argued that maintaining the dose limits necessary to protect humans will also result in the protection of most other species of flora and fauna. This concept is usually referred to as the anthropocentric approach. In other words, if man is protected then the environment is also adequately protected. The ecocentric approach might be stated as; the health of humans is effectively protected only when the environment is not unduly exposed to radiation. The ICRP is working on new recommendations dealing with the protection of the environment, and this debate should help to highlight a number of relevant issues concerning that topic.

  1. DARHT - an `adequate` EIS: A NEPA case study

    SciTech Connect

    Webb, M.D.

    1997-08-01

    The Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility Environmental Impact Statement (EIS) provides a case study that is interesting for many reasons. The EIS was prepared quickly, in the face of a lawsuit, for a project with unforeseen environmental impacts, for a facility that was deemed urgently essential to national security. Following judicial review the EIS was deemed to be {open_quotes}adequate.{close_quotes} DARHT is a facility now being built at Los Alamos National Laboratory (LANL) as part of the Department of Energy (DOE) nuclear weapons stockpile stewardship program. DARHT will be used to evaluate the safety and reliability of nuclear weapons, evaluate conventional munitions and study high-velocity impact phenomena. DARHT will be equipped with two accelerator-driven, high-intensity X-ray machines to record images of materials driven by high explosives. DARHT will be used for a variety of hydrodynamic tests, and DOE plans to conduct some dynamic experiments using plutonium at DARHT as well.

  2. ENSURING ADEQUATE SAFETY WHEN USING HYDROGEN AS A FUEL

    SciTech Connect

    Coutts, D

    2007-01-22

    Demonstration projects using hydrogen as a fuel are becoming very common. Often these projects rely on project-specific risk evaluations to support project safety decisions. This is necessary because regulations, codes, and standards (hereafter referred to as standards) are just being developed. This paper will review some of the approaches being used in these evolving standards, and techniques which demonstration projects can implement to bridge the gap between current requirements and stakeholder desires. Many of the evolving standards for hydrogen-fuel use performance-based language, which establishes minimum performance and safety objectives, as compared with prescriptive-based language that prescribes specific design solutions. This is being done for several reasons including: (1) concern that establishing specific design solutions too early will stifle invention, (2) sparse performance data necessary to support selection of design approaches, and (3) a risk-adverse public which is unwilling to accept losses that were incurred in developing previous prescriptive design standards. The evolving standards often contain words such as: ''The manufacturer shall implement the measures and provide the information necessary to minimize the risk of endangering a person's safety or health''. This typically implies that the manufacturer or project manager must produce and document an acceptable level of risk. If accomplished using comprehensive and systematic process the demonstration project risk assessment can ease the transition to widespread commercialization. An approach to adequately evaluate and document the safety risk will be presented.

  3. Quantifying variability within water samples: the need for adequate subsampling.

    PubMed

    Donohue, Ian; Irvine, Kenneth

    2008-01-01

    Accurate and precise determination of the concentration of nutrients and other substances in waterbodies is an essential requirement for supporting effective management and legislation. Owing primarily to logistic and financial constraints, however, national and regional agencies responsible for monitoring surface waters tend to quantify chemical indicators of water quality using a single sample from each waterbody, thus largely ignoring spatial variability. We show here that total sample variability, which comprises both analytical variability and within-sample heterogeneity, of a number of important chemical indicators of water quality (chlorophyll a, total phosphorus, total nitrogen, soluble molybdate-reactive phosphorus and dissolved inorganic nitrogen) varies significantly both over time and among determinands, and can be extremely high. Within-sample heterogeneity, whose mean contribution to total sample variability ranged between 62% and 100%, was significantly higher in samples taken from rivers compared with those from lakes, and was shown to be reduced by filtration. Our results show clearly that neither a single sample, nor even two sub-samples from that sample is adequate for the reliable, and statistically robust, detection of changes in the quality of surface waters. We recommend strongly that, in situations where it is practicable to take only a single sample from a waterbody, a minimum of three sub-samples are analysed from that sample for robust quantification of both the concentrations of determinands and total sample variability. PMID:17706740

  4. Structural Determination of Circulation.

    ERIC Educational Resources Information Center

    Blankenburg, William B.

    1981-01-01

    Analyzes the effects of both structural factors (demographics, economic conditions, and competition) and discretionary factors (content, design, and marketing techniques) and concludes that it is the former that determine a newspaper's circulation. (FL)

  5. Influence of simulated microgravity on clock genes expression rhythmicity and underlying blood circulating miRNAs-mRNA co-expression regulatory mechanism in C57BL/6J mice

    NASA Astrophysics Data System (ADS)

    Lv, Ke; Qu, Lina

    Purpose: It is vital for astronauts to maintain the optimal alertness and neurobehavioral function. Among various factors that exist in the space flight and long-duration mission environment, gravity changes may probably an essential environmental factor to interfere with internal circadian rhythms homeostasis and sleep quality, but the underlying mechanism is unclear. Mammals' biological clock is controlled by the suprachiasmatic nucleus (SCN), and peripheral organs adjust their own rhythmicity with the central signals. Nevertheless,the mechanism underlying this synchronizition process is still unknown. microRNAs (miRNAs) are about 19~22nt long regulatory RNAs that serve as critical modulators of post-transcriptional gene regulation. Recently, circulating miRNAs were found to have the regulatory role between cells and peripheral tissues, besides its function inside the cells. This study aims to investigate the regulatory signal transduction role of miRNAs between SCN and peripheral biological clock effecter tissues and to further decipher the mechanism of circadian disturbance under microgravity. Method: Firstly, based on the assumption that severe alterations in the expression of genes known to be involved in circadian rhythms may affect the expression of other genes, the labeled cDNA from liver and suprachiasmatic nucleus (SCN) of clock-knockout mice and control mice in different time points were cohybridized to microarrays. The fold change exceeding 2 (FC>2) was used to identify genes with altered expression levels in the knockout mice compared with control mice. Secondly, male C57BL/6J mice at 8 weeks of age were individually caged and acclimatized to the laboratory conditions (12h light/dark cycle) before being used for continuous core body temperature and activity monitoring. The mice were individually caged and tail suspended using a strip of adhesive surgical tape attached to a chain hanging from a pulley. Peripheral blood and liver tissues collection

  6. Atmospheric Circulation and Dynamics

    NASA Astrophysics Data System (ADS)

    Limaye, Sanjay S.; Rengel, Miriam

    The deep atmosphere of Venus ( ˜ 180 km including the thermosphere) presents both observational and modeling challenges. Its thick, nearly uniform global cloud cover makes it difficult to fathom the vertical structure of the global circulation through available techniques that are applied to Earth's atmosphere. Further, the slow rotation of the planet and the consequential prevailing cyclostrophic balance restricts easy inferences about the meridional flow and circulation (Gierasch et al. 1997, Read 1986, Schubert et al. 2007).

  7. [Changes of circulation, blood gases, acid-base-and metabolism during neurolept-analgesia with and without beta-receptor blockers in electro coagulation of Gasser's ganglion (author's transl)].

    PubMed

    Knitza, R; Olbermann, M; Fischer, F; Bässler, K H

    1978-05-01

    The cardiovascular, blood gas, acid-base and metabolic changes occurring during operative stress were studied in 10 elderly, metabolically healthy patients, suffering from idiopathic trigeminal neuralgia, who underwent electrocoagulation of the gasserian ganglion under neuroleptanalgesia. In a group of 12 patients undergoing the same operative procedure and anesthesthetic management, we investigated the effects of administration of a beta blocking agent on these parameters. Intraoperative rises of blood pressure and tachycardia were prevented by intravenous administration of 0.4 mg Pindolol (Visken), whereas increases in the blood glucose levels at the end of the operation were the same. The increase of glycerol, free fatty acids and ketone bodies was markedly reduced after pretreatment with the beta blocker compared with the controlgroup. In the patients without beta blocker treatment pH and standard bicarbonate at the end of the operation were lower as the result of the stimulation of ketogenesis. PMID:27127

  8. [Changes of circulation, blood gases, acid-base-and metabolism during neurolept-analgesia with and without beta-receptor blockers in electro coagulation of Gasser's ganglion (author's transl)].

    PubMed

    Knitza, R; Olbermann, M; Fischer, F; Bässler, K H

    1978-05-01

    The cardiovascular, blood gas, acid-base and metabolic changes occurring during operative stress were studied in 10 elderly, metabolically healthy patients, suffering from idiopathic trigeminal neuralgia, who underwent electrocoagulation of the gasserian ganglion under neuroleptanalgesia. In a group of 12 patients undergoing the same operative procedure and anesthesthetic management, we investigated the effects of administration of a beta blocking agent on these parameters. Intraoperative rises of blood pressure and tachycardia were prevented by intravenous administration of 0.4 mg Pindolol (Visken), whereas increases in the blood glucose levels at the end of the operation were the same. The increase of glycerol, free fatty acids and ketone bodies was markedly reduced after pretreatment with the beta blocker compared with the controlgroup. In the patients without beta blocker treatment pH and standard bicarbonate at the end of the operation were lower as the result of the stimulation of ketogenesis.

  9. Metastasis and Circulating Tumor Cells.

    PubMed

    van Dalum, Guus; Holland, Linda; Terstappen, Leon Wmm

    2012-10-01

    Cancer is a prominent cause of death worldwide. In most cases, it is not the primary tumor which causes death, but the metastases. Metastatic tumors are spread over the entire human body and are more difficult to remove or treat than the primary tumor. In a patient with metastatic disease, circulating tumor cells (CTCs) can be found in venous blood. These circulating tumor cells are part of the metastatic cascade. Clinical studies have shown that these cells can be used to predict treatment response and their presence is strongly associated with poor survival prospects. Enumeration and characterization of CTCs is important as this can help clinicians make more informed decisions when choosing or evaluating treatment. CTC counts are being included in an increasing number of studies and thus are becoming a bigger part of disease diagnosis and therapy management. We present an overview of the most prominent CTC enumeration and characterization methods and discuss the assumptions made about the CTC phenotype. Extensive CTC characterization of for example the DNA, RNA and antigen expression may lead to more understanding of the metastatic process.

  10. Metastasis and Circulating Tumor Cells

    PubMed Central

    van Dalum, Guus; Holland, Linda

    2012-01-01

    Cancer is a prominent cause of death worldwide. In most cases, it is not the primary tumor which causes death, but the metastases. Metastatic tumors are spread over the entire human body and are more difficult to remove or treat than the primary tumor. In a patient with metastatic disease, circulating tumor cells (CTCs) can be found in venous blood. These circulating tumor cells are part of the metastatic cascade. Clinical studies have shown that these cells can be used to predict treatment response and their presence is strongly associated with poor survival prospects. Enumeration and characterization of CTCs is important as this can help clinicians make more informed decisions when choosing or evaluating treatment. CTC counts are being included in an increasing number of studies and thus are becoming a bigger part of disease diagnosis and therapy management. We present an overview of the most prominent CTC enumeration and characterization methods and discuss the assumptions made about the CTC phenotype. Extensive CTC characterization of for example the DNA, RNA and antigen expression may lead to more understanding of the metastatic process. PMID:27683421

  11. Metastasis and Circulating Tumor Cells

    PubMed Central

    van Dalum, Guus; Holland, Linda

    2012-01-01

    Cancer is a prominent cause of death worldwide. In most cases, it is not the primary tumor which causes death, but the metastases. Metastatic tumors are spread over the entire human body and are more difficult to remove or treat than the primary tumor. In a patient with metastatic disease, circulating tumor cells (CTCs) can be found in venous blood. These circulating tumor cells are part of the metastatic cascade. Clinical studies have shown that these cells can be used to predict treatment response and their presence is strongly associated with poor survival prospects. Enumeration and characterization of CTCs is important as this can help clinicians make more informed decisions when choosing or evaluating treatment. CTC counts are being included in an increasing number of studies and thus are becoming a bigger part of disease diagnosis and therapy management. We present an overview of the most prominent CTC enumeration and characterization methods and discuss the assumptions made about the CTC phenotype. Extensive CTC characterization of for example the DNA, RNA and antigen expression may lead to more understanding of the metastatic process.

  12. Blood groups and filariasis.

    PubMed

    Kumar, H; Santhanam, S

    1989-01-01

    Only a little is known about the studies done with filariasis in relation to blood groups. The present communication reports the results of a preliminary study carried out to investigate any relationship of ABO and Rho(D) blood groups in persons with circulating microfilariae (mf) in blood and with disease manifestations compared with healthy normal controls within a population in similar epidemiological and ecological conditions. Blood groups ABO and Rho(D) were investigated among 271 persons with filarial disease and 172 normal subjects from an endemic area of bancroftian filariasis. No relationship was observed between infection and blood groups. It appeared that blood groups and filarial infection were independent of each other. Also the sex of the individual and stage of the infection, i.e. persons with circulating mf only without manifestations and persons with established manifestation without mf, has no bearing on blood group inheritance. There were 95.05% of Rh-positive and 4.95% of Rh-negative persons in the whole studied population. The observations are similar to other studies.

  13. On Adequate Comparisons of Antenna Phase Center Variations

    NASA Astrophysics Data System (ADS)

    Schoen, S.; Kersten, T.

    2013-12-01

    One important part for ensuring the high quality of the International GNSS Service's (IGS) products is the collection and publication of receiver - and satellite antenna phase center variations (PCV). The PCV are crucial for global and regional networks, since they introduce a global scale factor of up to 16ppb or changes in the height component with an amount of up to 10cm, respectively. Furthermore, antenna phase center variations are also important for precise orbit determination, navigation and positioning of mobile platforms, like e.g. the GOCE and GRACE gravity missions, or for the accurate Precise Point Positioning (PPP) processing. Using the EUREF Permanent Network (EPN), Baire et al. (2012) showed that individual PCV values have a significant impact on the geodetic positioning. The statements are further supported by studies of Steigenberger et al. (2013) where the impact of PCV for local-ties are analysed. Currently, there are five calibration institutions including the Institut für Erdmessung (IfE) contributing to the IGS PCV file. Different approaches like field calibrations and anechoic chamber measurements are in use. Additionally, the computation and parameterization of the PCV are completely different within the methods. Therefore, every new approach has to pass a benchmark test in order to ensure that variations of PCV values of an identical antenna obtained from different methods are as consistent as possible. Since the number of approaches to obtain these PCV values rises with the number of calibration institutions, there is the necessity for an adequate comparison concept, taking into account not only the numerical values but also stochastic information and computational issues of the determined PCVs. This is of special importance, since the majority of calibrated receiver antennas published by the IGS origin from absolute field calibrations based on the Hannover Concept, Wübbena et al. (2000). In this contribution, a concept for the adequate

  14. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment.

  15. Are women with psychosis receiving adequate cervical cancer screening?

    PubMed Central

    Tilbrook, Devon; Polsky, Jane; Lofters, Aisha

    2010-01-01

    ABSTRACT OBJECTIVE To investigate the rates of cervical cancer screening among female patients with psychosis compared with similar patients without psychosis, as an indicator of the quality of primary preventive health care. DESIGN A retrospective cohort study using medical records between November 1, 2004, and November 1, 2007. SETTING Two urban family medicine clinics associated with an academic hospital in Toronto, Ont. PARTICIPANTS A random sample of female patients with and without psychosis between the ages of 20 and 69 years. MAIN OUTCOME MEASURES Number of Papanicolaou tests in a 3-year period. RESULTS Charts for 51 female patients with psychosis and 118 female patients without psychosis were reviewed. Of those women with psychosis, 62.7% were diagnosed with schizophrenia, 19.6% with bipolar disorder, 17.6% with schizoaffective disorder, and 29.4% with other psychotic disorders. Women in both groups were similar in age, rate of comorbidities, and number of full physical examinations. Women with psychosis were significantly more likely to smoke (P < .0001), to have more primary care appointments (P = .035), and to miss appointments (P = .0002) than women without psychosis. After adjustment for age, other psychiatric illnesses, number of physical examinations, number of missed appointments, and having a gynecologist, women with psychosis were significantly less likely to have had a Pap test in the previous 3 years compared with women without psychosis (47.1% vs 73.7%, respectively; odds ratio 0.19, 95% confidence interval 0.06 to 0.58). CONCLUSION Women with psychosis are more than 5 times less likely to receive adequate Pap screening compared with the general population despite their increased rates of smoking and increased number of primary care visits. PMID:20393098

  16. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment. PMID:26068436

  17. Caffeine induced changes in cerebral circulation

    SciTech Connect

    Mathew, R.J.; Wilson, W.H.

    1985-09-01

    While the caffeine induced cerebral vasoconstriction is well documented, the effects of oral ingestion of the drug in a dose range comparable to the quantities in which it is usually consumed and the intensity and duration of the associated reduction in cerebral circulation are unknown. Cerebral blood flow was measured via the TTXenon inhalation technique before and thirty and ninety minutes after the oral administration of 250 mg of caffeine or a placebo, under double-blind conditions. Caffeine ingestion was found to be associated with significant reductions in cerebral perfusion thirty and ninety minutes later. The placebo group showed no differences between the three sets of cerebral blood flow values.

  18. [Hyperdynamic circulation in patients with liver cirrhosis and portal hypertension].

    PubMed

    Kim, Moon Young; Baik, Soon Koo

    2009-09-01

    Hyperdynamic circulation in patients with liver cirrhosis is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure and currently focused on understanding the pathogenesis because of possibility of developing novel treatment modality. Basically, these hemodynamic alternations arise from portal hypertension. Portosystemic collaterals develop to counterbalance the increased intrahepatic vascular resistance to portal blood flow and induce an increase in venous return to heart. Increased shear stress in vascular endothelial cell related high blood flow by portosystemic shunting contributes to this upregulation of eNOS resulting in NO overproduction. Additionally, bypassing through portosystemic collaterals and escaping degradation of over-produced circulating vasodilators in the diseased liver can promote the peripheral arterial vasodilation. Vasodilation of the systemic and splanchnic circulations lead to a reduced systemic vascular resistance, and increased cardiac output and splanchnic blood flow. Furthermore, neurohumoral vasoconstrictive systems including systemic nervous system, rennin angiotensin aldosterone system, and vasopressin are intensively activated secondary to vasodilation. However, hyperdynamic circulation would be more aggravated by the activated vasoconstrictive systems. With the progression of the cirrhotic process, hyperdynamic alternations can be more profound due to hyporesponsiveness to vasoconstrictors and increased shunt formation in conjunction with autonomic neuropathy. Eventually, splanchnic arterial vasodilation results in an increase portal venous inflow, maintaining the elevated portal venous pressure. Hyperdynamic circulation is intimately involved in portal hypertension with liver cirrhosis, therefore it is reasonable to have an interest in complete understanding of the pathogenesis of hyperdynamic circulation to develop novel treatment modality.

  19. Vomiting blood

    MedlinePlus

    ... first part of the small intestine, or esophagus Blood clotting disorders Defects in the blood vessels of the ... as a complete blood count (CBC), blood chemistries, blood clotting tests, and liver function tests Esophagogastroduodenoscopy (EGD) (placing ...

  20. Blood Disorders

    MedlinePlus

    ... liquid part, called plasma, is made of water, salts and protein. Over half of your blood is plasma. The solid part of your blood contains red blood cells, white blood cells and platelets. Blood disorders affect ...

  1. Blood bank regulations in India.

    PubMed

    Choudhury, Nabajyoti; Desai, Priti

    2012-06-01

    Successful blood services depend on legally empowered regulatory services. Blood transfusion services are important constituents of national health services. Blood transfusion services in India are regulated by the Drugs and Cosmetics Act, 1940 and its subsequent amendments. The Drugs and Cosmetics Act, 1940 specifies about accommodation, manpower, equipment, supplies and reagents, good manufacturing practices, and process control to be followed in Indian blood transfusion services.Regulatory affairs in the Indian blood banking system are controlled by central and provincial Drug Control authority under Drug Controller General of India. National AIDS Control Organization (NACO) acts as a facilitator to Indian blood transfusion services on behalf of the Ministry of Health and Family Welfare, Government of India,especially to the government sector. The National Blood Policy was published by the Government of India in 2002 and it provides objectives to provide safe, adequate quantity of blood, blood components, and products.

  2. [Are legal sanctions for improving traffic safety adequate?].

    PubMed

    Geppert, K

    1990-01-01

    Referring to the field of traffic legislation the author examines the different possibilities to improve the safety on the road, within the corresponding range of summary offence and criminal law; (1) As far as the rules of conduct are concerned he demands a uniform threshold value of at least 0.8% for blood alcohol within the limits of the German penal code Sections 315 c I, 316. He rejects the plan to introduce a criminal offence of considerable speeding if imminent danger is provoked. (2) On the level of sanctions the traditional measures of traffic legislation are to be supplied sensibly by supplementary training courses concerning alcohol abuse. The legal instruments of (temporary) suspension of a person's driving license on the part of criminal jurisdiction or public authorities ought to be utilized on a larger scale. The (Flensburg) repeated perpetration point system is to be improved with regard to special preventive measures. (3) To increase the risk of being caught the control of the traffic by the police is to be intensified--especially through a larger application of technical means. (4) The extension of the instruments of traffic legislation to immediate measures by the police--preliminary or "mini" suspension of a person's driving license by resort to preventive rights by the police?--meets with constitutional or legal scruples.

  3. Screening and identification of differentially expressed transcripts in circulating cells of prostate cancer patients using suppression subtractive hybridization

    PubMed Central

    Li, Xin; Wong, Carson; Mysel, Ralph; Slobodov, Gennady; Metwalli, Adam; Kruska, Jarrett; Manatt, C Scott; Culkin, Daniel J; Kropp, Bradley P; Lin, Hsueh-Kung

    2005-01-01

    Background Tumor metastasis and changes in host immunosurveillance are important components in cancer development. Tumor cell invasion into the bloodstream is an essential step for systemic metastasis. Currently, the detection of tumor cells in the circulation is mainly dependent upon the utilization of known epithelial cell markers. However, expression of these molecules is not limited to cancer patients; healthy people also have a small number of epithelial cells in their circulation. Utilizing these markers to detect circulating tumor cells (CTCs) cannot adequately explain the mechanisms of tumor cell survival or their development of metastatic potential in peripheral blood. The immune system can also evolve along with the cancer, actually promoting or selecting the outgrowth of tumor variants. Unfortunately, both metastasis and immunosurveillance remain mysterious and are debatable because we have yet to define the molecules that participate in these processes. We are interested in identifying the existence of expressed genes, or mRNA species, that are specifically associated with circulating cells of cancer-bearing patients using prostate cancer (PCa) as a model. Results We established two comprehensive subtracted cDNA libraries using a molecular technique called suppression subtractive hybridization. This technique selectively amplifies transcripts that are specifically expressed in circulating cells of either PCa patients or healthy men. Following sequencing reaction, we showed that 17 out of 23 (73.9%) sequenced clones did not match any mRNAs in the GenBank database. This result suggests that genes associated with alterations in circulating cells of cancer-bearing patients are largely unknown. Semi-quantitative RT-PCR confirmed that two genes are up-regulated in circulating cells of PCa patients, whereas another two genes are down-regulated in the same patients. Conclusion The comprehensive gene expression analysis is capable of identifying differentially

  4. Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility.

    PubMed

    Ignatiadis, Michail; Lee, Mark; Jeffrey, Stefanie S

    2015-11-01

    Recent technological advances have enabled the detection and detailed characterization of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) in blood samples from patients with cancer. Often referred to as a "liquid biopsy," CTCs and ctDNA are expected to provide real-time monitoring of tumor evolution and therapeutic efficacy, with the potential for improved cancer diagnosis and treatment. In this review, we focus on these opportunities as well as the challenges that should be addressed so that these tools may eventually be implemented into routine clinical care.

  5. On the North Atlantic circulation

    SciTech Connect

    Schmitz, W.J. Jr.; McCartney, M.S. )

    1993-02-01

    A summary for North Atlantic circulation is proposed to replace the circulation scheme hypothesized by Worthington in 1976. Divergences from the previous model are in thermohaline circulation, cross-equatorical transport and Florida Current sources, flow in the eastern Atlantic, circulation in the Newfoundland Basin, slope water currents, and flow pattern near the Bahamas. The circulation patterns presented here are consistent with the majority of of published accounts of flow components. 77 refs., 14 figs., 3 tabs.

  6. Adequate iron stores and the 'Nil nocere' principle.

    PubMed

    Hollán, S; Johansen, K S

    1993-01-01

    There is a need to change the policy of unselective iron supplementation during periods of life with physiologically increased cell proliferation. Levels of iron stores to be regarded as adequate during infancy and pregnancy are still not well established. Recent data support the view that it is not justified to interfere with physiological adaptations developed through millions of years by sophisticated and precisely coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regulates the expression of proteins with central importance in cellular iron metabolism (TfR, ferritin, and erythroid 5-aminolevulinic synthetase) in a coordinately controlled way through an iron dependent cytosolic mRNA binding protein, the iron regulating factor (IRF). This factor is simultaneously a sensor and a regulator of iron levels. The reduction of ferritin levels during highly increased cell proliferation is a mirror of the increased density of TfRs. An abundance of data support the vigorous competition for growth-essential iron between microbial pathogens and their vertebrate hosts. The highly coordinated regulation of iron metabolism is probably crucial in achieving a balance between the blockade of readily accessible iron to invading organisms and yet providing sufficient iron for the immune system of the host. The most evident adverse clinical effects of excess iron have been observed in immunodeficient patients in tropical countries and in AIDS patients. Excess iron also increases the risk of initiation and promotion of malignant processes by iron binding to DNA and by the iron-catalysed release of free radicals. Oxygen radicals were shown to damage critical biomolecules leading, apart from cancer, to a variety of human disease states, including inflammation and atherosclerosis. They are also involved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron

  7. Central and coronary circulation of the normal man during orthostatic and lower body negative pressure tests.

    PubMed

    Katkov, V E; Chestukhin, V V; Kakurin, L I; Babin, A M; Nikolaenko, E M

    1987-09-01

    The effects of the tilt test (at 60-70 degrees for 20 min) and LBNP test (at -30 and -60 mm Hg for 20 min each) on the basic parameters of central circulation (15 test subjects) and coronary circulation (11 test subjects) were investigated. The study was performed using thermistor-equipped catheters implanted into the pulmonary artery and coronary sinus and Teflon catheters implanted into the brachial artery. In the study, the basic parameters of central circulation (pressure in the right atrium and pulmonary artery, transmural pressure in these compartments, cardiac index, stroke index, etc.) and coronary circulation (blood flow in the coronary sinus, left ventricle oxygen consumption, coronary resistance, etc.) were measured. Correlation between circulation variations and metabolic requirements was assessed (with respect to changes in acid-base equilibrium of blood). The effect of the tilt test and LBNP test on the basic parameters of central and coronary circulation, blood acid-base equilibrium and oxygenation was compared.

  8. A probe for blood-vessel and spinal interiors

    NASA Technical Reports Server (NTRS)

    Frazer, R. E.

    1978-01-01

    Probe design allows insertion into lumen of blood vessels to perform oximetry and investigate plaque on interior vessel walls. Probe is more accurate than standard oximetry procedures of determining oxygenation of circulating blood.

  9. Synthesis of the blood circulating C-terminal fragment of insulin-like growth factor (IGF)-binding protein-4 in its native conformation. Crystallization, heparin and IGF binding, and osteogenic activity.

    PubMed

    Fernández-Tornero, Carlos; Lozano, Rosa M; Rivas, Germán; Jiménez, M Angeles; Ständker, Ludger; Díaz-Gonzalez, Diana; Forssmann, Wolf-Georg; Cuevas, Pedro; Romero, Antonio; Giménez-Gallego, Guillermo

    2005-05-13

    Insulin-like growth factor-binding proteins play a critical role in a wide variety of important physiological processes. It has been demonstrated that both an N-terminal and a C-terminal fragment of insulin-like growth factor-binding protein-4 exist and accumulate in the circulatory system, these fragments accounting for virtually the whole amino acid sequence of the protein. The circulating C-terminal fragment establishes three disulfide bridges, and the binding pattern of these has recently been defined. Here we show that the monodimensional 1H NMR spectrum of the C-terminal fragment is typical of a protein with a relatively close packed tertiary structure. This fragment can be produced in its native conformation in Escherichia coli, without the requirement of further refolding procedures, when synthesis is coupled to its secretion from the cell. The recombinant protein crystallizes with the unit cell parameters of a hexagonal system. Furthermore, it binds strongly to heparin, acquiring a well defined oligomeric structure that interacts with insulin-like growth factors, and promotes bone formation in cultures of murine calvariae.

  10. Arctic circulation regimes.

    PubMed

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L

    2015-10-13

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. PMID:26347536

  11. Arctic circulation regimes

    PubMed Central

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L.

    2015-01-01

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. PMID:26347536

  12. Circulation and Finding System.

    ERIC Educational Resources Information Center

    Pierce, A. R.

    This report describes an online minicomputer-based system, one combining library inventory control with catalog access, that was implemented at Virginia Tech's main library in order to meet the demands of increased circulation activity and rising staff costs. Following overviews of the institutional environment, the systems development department,…

  13. Portable oven air circulator

    DOEpatents

    Jorgensen, Jorgen A.; Nygren, Donald W.

    1983-01-01

    A portable air circulating apparatus for use in cooking ovens which is used to create air currents in the oven which transfer heat to cooking foodstuffs to promote more rapid and more uniform cooking or baking, the apparatus including a motor, fan blade and housing of metallic materials selected from a class of heat resistant materials.

  14. Circulation Aide Training Manual.

    ERIC Educational Resources Information Center

    Bergeson, Alan O.

    This training manual provides instruction on shelving and other duties for student assistants in the learning resources center at the College of Dupage, located in Illinois. It is noted that prospective student circulation aides are required to read the manual and pass a written test on policies and procedures before they are allowed to shelve…

  15. [Local blood circulation, uptake of 45Ca, 85Sr and 3H-proline and mineral levels in the tibia of female rats: comparison and changes after administration of estradiol].

    PubMed

    Kapitola, J; Andrle, J; Kubícková, J

    1993-01-01

    After six weeks' administration of estradiol benzoate (Agofollin Depot, 1 mg s.c. once a week) we determined in the first part of 70 days old female rats the uptake of 85Sr-microspheres and local blood flow in the tibia, in the second part 24 hours' incorporation of 45Ca and 3H-proline and in the third part 2 hours' uptake of 85Sr, bone density and ash weight related to 1 ml of bone volume. We observed the following statistically significant changes: decrease in the uptake of 85Sr-microspheres and local blood flow, decrease in the incorporation of 45Ca, 3H-proline and 85Sr, increase in the density and ash weight of the tibia. The rise of bone mineral content simultaneously with reduced indicators of bone formation and particularly of the mineralization seems to be in the connection with the suppression of bone resorption under the influence of estrogen. Qualitatively identical reactions of circulatory and metabolic indicators to the administration of estradiol may be a reflection of mutual physiological interconnections. PMID:7973417

  16. Particle-based methods for multiscale modeling of blood flow in the circulation and in devices: challenges and future directions. Sixth International Bio-Fluid Mechanics Symposium and Workshop March 28-30, 2008 Pasadena, California.

    PubMed

    Yamaguchi, Takami; Ishikawa, Takuji; Imai, Y; Matsuki, N; Xenos, Mikhail; Deng, Yuefan; Bluestein, Danny

    2010-03-01

    A major computational challenge for a multiscale modeling is the coupling of disparate length and timescales between molecular mechanics and macroscopic transport, spanning the spatial and temporal scales characterizing the complex processes taking place in flow-induced blood clotting. Flow and pressure effects on a cell-like platelet can be well represented by a continuum mechanics model down to the order of the micrometer level. However, the molecular effects of adhesion/aggregation bonds are on the order of nanometer. A successful multiscale model of platelet response to flow stresses in devices and the ensuing clotting responses should be able to characterize the clotting reactions and their interactions with the flow. This paper attempts to describe a few of the computational methods that were developed in recent years and became available to researchers in the field. They differ from traditional approaches that dominate the field by expanding on prevailing continuum-based approaches, or by completely departing from them, yielding an expanding toolkit that may facilitate further elucidation of the underlying mechanisms of blood flow and the cellular response to it. We offer a paradigm shift by adopting a multidisciplinary approach with fluid dynamics simulations coupled to biophysical and biochemical transport.

  17. Blood clotting

    MedlinePlus Videos and Cool Tools

    ... the external bleeding stops. Clotting factors in the blood cause strands of blood-borne material, called fibrin, to stick together and ... the inside of the wound. Eventually, the cut blood vessel heals, and the blood clot dissolves after ...

  18. Circulation in a Short Cylindrical Couette System

    SciTech Connect

    Akira Kageyama; Hantao Ji; Jeremy Goodman

    2003-07-08

    In preparation for an experimental study of magnetorotational instability (MRI) in liquid metal, we explore Couette flows having height comparable to the gap between cylinders, centrifugally stable rotation, and high Reynolds number. Experiments in water are compared with numerical simulations. The flow is very different from that of an ideal, infinitely long Couette system. Simulations show that endcaps co-rotating with the outer cylinder drive a strong poloidal circulation that redistributes angular momentum. Predicted toroidal flow profiles agree well with experimental measurements. Spin-down times scale with Reynolds number as expected for laminar Ekman circulation; extrapolation from two-dimensional simulations at Re less than or equal to 3200 agrees remarkably well with experiment at Re approximately equal to 106. This suggests that turbulence does not dominate the effective viscosity. Further detailed numerical studies reveal a strong radially inward flow near both endcaps. After turning vertically along the inner cylinder, these flows converge at the midplane and depart the boundary in a radial jet. To minimize this circulation in the MRI experiment, endcaps consisting of multiple, differentially rotating rings are proposed. Simulations predict that an adequate approximation to the ideal Couette profile can be obtained with a few rings.

  19. Immune Cells in Blood Recognize Tumors

    Cancer.gov

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  20. Circulating tumour cells and circulating nucleic acids as a measure of tumour dissemination in non-metastatic colorectal cancer surgery.

    PubMed

    Lim, S H; Spring, K J; de Souza, P; MacKenzie, S; Bokey, L

    2015-03-01

    There is accumulating evidence for circulating tumour cells (CTCs) and circulating tumour nucleic acids (ctNAs) as prognostic and predictive biomarkers in colorectal cancer. Their role in the perioperative setting is evolving. These blood-borne biomarkers can potentially demonstrate tumour dissemination at time of colorectal cancer surgery and estimate the completeness of a surgical resection. CTCs and circulating ctNA levels at time of surgery, and persistent levels post-surgery, may correlate with poorer patient outcomes. These biomarkers can be utilised to refine surgical techniques to minimise tumour dissemination and determine the need for adjuvant therapy.

  1. Determining median urinary iodine concentration that indicates adequate iodine intake at population level.

    PubMed Central

    Delange, François; de Benoist, Bruno; Burgi, Hans

    2002-01-01

    OBJECTIVE: Urinary iodine concentration is the prime indicator of nutritional iodine status and is used to evaluate population-based iodine supplementation. In 1994, WHO, UNICEF and ICCIDD recommended median urinary iodine concentrations for populations of 100- 200 micro g/l, assuming the 100 micro g/l threshold would limit concentrations <50 micro g/l to circulated to 29 scientific groups. FINDINGS: Nineteen groups reported data from 48 populations with median urinary iodine concentrations >100 micro g/l. The total population was 55 892, including 35 661 (64%) schoolchildren. Median urinary iodine concentrations were 111-540 (median 201) micro g/l for all populations, 100-199 micro g/l in 23 (48%) populations and >/=200 micro g/l in 25 (52%). The frequencies of values <50 micro g/l were 0-20.8 (mean 4.8%) overall and 7.2% and 2.5% in populations with medians of 100-199 micro g/l and >200 micro g/l, respectively. The frequency reached 20% only in two places where iodine had been supplemented for <2 years. CONCLUSION: The frequency of urinary iodine concentrations <50 micro g/l in populations with median urinary iodine concentrations >/=100 micro g/l has been overestimated. The threshold of 100 micro g/l does not need to be increased. In populations, median urinary iodine concentrations of 100-200 micro g/l indicate adequate iodine intake and optimal iodine nutrition. PMID:12219154

  2. Improved in vivo imaging of human blood circulation in the chorioretinal complex using phase variance method with new phase stabilized 1 μm swept-source optical coherence tomography (pv-SSOCT)

    NASA Astrophysics Data System (ADS)

    Poddar, Raju; Kim, Dae Yu; Werner, John S.; Zawadzki, Robert J.

    2014-02-01

    We demonstrate the feasibility of our newly developed phase stabilized high-speed (100 kHz A-scans/s) 1 μm sweptsource optical coherence tomography (SSOCT) system with the phase-variance based motion contrast method for visualization of human chorioretinal complex microcirculation. Compared to our previously reported spectral domain (spectrometer based) phase-variance (pv)-SDOCT system it has advantages of higher sensitivity, reduced fringe washout for high blood flow speeds and deeper penetration in choroid. High phase stability SSOCT imaging was achieved by using a computationally efficient phase stabilization approach. This process does not require additional calibration hardware and complex numerical procedures. Our phase stabilization method is simple and can be employed in a variety of SS-OCT systems. Examples of vasculature in the chorioretinal complex imaged by pv-SSOCT is presented and compared to retinal images of the same volunteers acquired with fluorescein angiography (FA) and indocyanine green angiography (ICGA).

  3. Circulating tumor cells in colorectal cancer patients.

    PubMed

    Torino, Francesco; Bonmassar, Enzo; Bonmassar, Laura; De Vecchis, Liana; Barnabei, Agnese; Zuppi, Cecilia; Capoluongo, Ettore; Aquino, Angelo

    2013-11-01

    The availability of sensitive methods has allowed the detailed study of circulating tumor cells only recently. Evolving evidence support the prognostic and predictive role of these cells in patients affected by several solid tumors, including colorectal cancer. Ongoing studies are aimed at confirming that the molecular characterization of circulating tumor cells in peripheral blood and in bone marrow of patients is a powerful tool to improve the patient risk-stratification, to monitor activity of the drugs, to develop more appropriate targeted therapies and tailored treatments. In parallel, results from these correlative studies promise to gain a better biological understanding of the metastatic process. The clinical utility of the detection of circulating tumor cells in patients affected by colorectal cancer is still hampered by a number of specific hurdles. Improvement in sensitivity and specificity of the available methods of detection, standardization of these methods and functional characterization of circulating tumor cells in well designed and statistically well powered studies are the key steps to reach these ambitious objectives in colorectal cancer patients as well.

  4. [Circulating "tumor markers" in gastrointestinal tumors].

    PubMed

    Borlinghaus, P; Lamerz, R

    1991-09-01

    Tumor markers (TM) of the neoplastic cell can be divided into non-shedded substances and antigens shedded in blood, urine or other body fluids. For clinicians circulating TM are more important. All relevant circulating TM are not useful in screening of asymptomatic patients because of insufficient sensitivity and specificity. With caution they are useful in the observation of risk groups. Circulating TM have their main significance as additional parameters in monitoring symptomatic patients with malignancies. Several follow up determinations are more important than one single measurement. During follow up of tumor patients TM should not be checked automatically if there are no diagnostic or therapeutical consequences. The clinically most important circulating TM in non-hormone secreting tumors of the gastrointestinal tract are the oncofetal antigens CEA and AFP and antigens defined by monoclonal antibodies e. g. CA 19-9 and CA 72-4. AFP is the primary TM in hepatocellular carcinoma, often elevated in hepatoblastoma and always normal in cholangiocellular carcinoma. CEA is the TM of first choice in patients with colorectal carcinomas and liver metastasis. CA 19-9 is TM of first choice in pancreatic carcinoma and additionally of diagnostic value in cholangiocellular carcinoma and tumors of the bile ducts. In cancer of the stomach CA 19-9 and CEA are secondary TM in combination with CA 72-4 as primary TM. Care should be taken that slight and moderate elevations of TM can be observed in benign diseases of liver, pancreas and bowel.

  5. Circulation-Enhancing Device Improves CPR

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Advanced Circulatory Systems, Inc. and NASA's Kennedy Space Center collaborated for five years on impedance threshold device technology. The resulting technology is encapsulated in a device called the ResQPOD Circulatory Enhancer, which improves the standard of care provided to patients with a variety of clinical conditions due to low blood flow. ResQPOD generates negative intrathoracic pressure during respiration to increase blood flow to the body's vital organs. It is unique in that it non-invasively enhances the body's biophysical performance without depending on pharmaceutical or other outside agents. ResQPOD uses the relationship of the heart, brain, lungs and chest cavity in a manner similar to a bellows to increase venous blood return to the heart. Multiple studies have shown a significant improvement in cardiac output and blood flow to the brain with the use of the impedance threshold device, as well as the device's ability to prevent shock secondary to blood loss. ResQPOD has been added to the set of medical equipment that is available for returning astronaut crews, and commercial applications have fallen into two categories: Non-spontaneously breathing patients who can benefit from enhanced circulation, and spontaneously breathing patients who suffer from transient hypotension or low blood pressure.

  6. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  7. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  8. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  9. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  10. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  11. Circulating Tumor Cells.

    PubMed

    Paoletti, Costanza; Hayes, Daniel F

    2016-01-01

    Circulating Tumor Cells (CTC) are shed from primary or secondary tumors. Prior studies have demonstrated that enumeration of CTC is a robust independent prognostic factor of progression free and overall survival in patients with early and metastatic breast cancer. CTC, as well as other circulating tumor markers, have the appealing advantages over tissue biopsy of (1) ease of collection, (2) serial evaluation, and (3) interrogation of the entire tumor burden instead of just a limited part of the tumor. Advances have been recently made in phenotyping and genotyping of CTC, which should provide insights into the predictive role of CTC for sensitivity or resistance to therapies. In addition, CTC phenotypic marker changes during the course of treatment may serve as pharmacodynamic monitoring tools. Therefore, CTC may be considered "liquid biopsies," providing prognostic and predictive clinical information as well as additional understanding of tumor heterogeneity.

  12. Ocean circulation studies

    NASA Technical Reports Server (NTRS)

    Koblinsky, C. J.

    1984-01-01

    Remotely sensed signatures of ocean surface characteristics from active and passive satellite-borne radiometers in conjunction with in situ data were utilized to examine the large scale, low frequency circulation of the world's oceans. Studies of the California Current, the Gulf of California, and the Kuroshio Extension Current in the western North Pacific were reviewed briefly. The importance of satellite oceanographic tools was emphasized.

  13. Circulating cancer stem cells: the importance to select

    PubMed Central

    Yang, Ming-Hsin; Imrali, Ahmet

    2015-01-01

    It has been demonstrated that even localized tumors without clinically apparent metastasis give rise to circulating tumor cells (CTCs). A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients’ outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, ‘liquid biopsy’, which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis-initiating capabilities based on their stemness properties and invasiveness and thus are critical for the patients’ clinical outcome. As compared to non-tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and

  14. Twenty-Four-Hour Urine Osmolality as a Physiological Index of Adequate Water Intake

    PubMed Central

    Perrier, Erica T.; Buendia-Jimenez, Inmaculada; Vecchio, Mariacristina; Armstrong, Lawrence E.; Tack, Ivan; Klein, Alexis

    2015-01-01

    While associations exist between water, hydration, and disease risk, research quantifying the dose-response effect of water on health is limited. Thus, the water intake necessary to maintain optimal hydration from a physiological and health standpoint remains unclear. The aim of this analysis was to derive a 24 h urine osmolality (UOsm) threshold that would provide an index of “optimal hydration,” sufficient to compensate water losses and also be biologically significant relative to the risk of disease. Ninety-five adults (31.5 ± 4.3 years, 23.2 ± 2.7 kg·m−2) collected 24 h urine, provided morning blood samples, and completed food and fluid intake diaries over 3 consecutive weekdays. A UOsm threshold was derived using 3 approaches, taking into account European dietary reference values for water; total fluid intake, and urine volumes associated with reduced risk for lithiasis and chronic kidney disease and plasma vasopressin concentration. The aggregate of these approaches suggest that a 24 h urine osmolality ≤500 mOsm·kg−1 may be a simple indicator of optimal hydration, representing a total daily fluid intake adequate to compensate for daily losses, ensure urinary output sufficient to reduce the risk of urolithiasis and renal function decline, and avoid elevated plasma vasopressin concentrations mediating the increased antidiuretic effort. PMID:25866433

  15. Modulation of splanchnic circulation: Role in perioperative management of liver transplant patients.

    PubMed

    Mukhtar, Ahmed; Dabbous, Hany

    2016-01-28

    Splanchnic circulation is the primary mechanism that regulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods (e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure. PMID:26819524

  16. Migration and circulation in Ecuador.

    PubMed

    Brea, J A

    1991-01-01

    "This study investigates labor mobility in Ecuador as a function of the socioeconomic structure of places and personal attributes of migrants and circulators (short-term movers).... Particular attention is given to the role of agrarian change in altering established migration and circulation patterns." The author finds that "circulation may significantly alter family organization and the role of women in many Ecuadorian communities."

  17. Library Circulation Systems: An Overview

    ERIC Educational Resources Information Center

    Surace, Cecily J.

    1972-01-01

    The model circulation system outlined is an on-line real time system in which the circulation file is created from the shelf list. The model extends beyond the operational limits of most existing circulation systems and can be considered a reflection of the current state of the art. (36 references) (Author/NH)

  18. Influence of age, systemic blood pressure, smoking, and blood viscosity on orbital blood velocities.

    PubMed Central

    Williamson, T H; Lowe, G D; Baxter, G M

    1995-01-01

    The influence of multiple systemic factors upon the blood velocities obtained from the orbital circulations was investigated. The velocities obtained by colour Doppler imaging from the ophthalmic artery, central retinal artery, and vein from 95 ophthalmologically healthy volunteers were analyzed. The effects of age, systemic blood pressure, and smoking habit were examined. In 24 volunteers blood viscosity was also measured and its relation with blood velocity assessed. Age was weakly negatively correlated with the blood velocities in the ophthalmic artery and weakly positively correlated with resistance to flow in the retinal circulation. Systolic blood pressure showed a positive correlation with the peak systolic velocities in the arteries while cigarette smoking was associated with lower ophthalmic artery velocities. Increased haematocrit and viscosity were positively correlated with resistance to flow proximal to the ophthalmic artery and red cell rigidity negatively correlated with the pulsatility of flow in the retinal vein. These results help to identify the roles of systemic conditions in the ocular circulation. The influence of blood viscosity on retinal venous flow may be relevant to the pathogenetic mechanisms of conditions such as central retinal vein occlusion. Images PMID:7880783

  19. Molecular diagnosis of toxoplasmosis: value of the buffy coat for the detection of circulating Toxoplasma gondii.

    PubMed

    Brenier-Pinchart, Marie-Pierre; Capderou, Elodie; Bertini, Rose-Laurence; Bailly, Sébastien; Fricker-Hidalgo, Hélène; Varlet-Marie, Emmanuelle; Murat, Jean-Benjamin; Sterkers, Yvon; Touafek, Fériel; Bastien, Patrick; Pelloux, Hervé

    2015-08-01

    Early detection of Toxoplasma tachyzoites circulating in blood using PCR is recommended for immunosuppressed patients at high risk for disseminated toxoplasmosis. Using a toxoplasmosis mouse model, we show that the sensitivity of detection is higher using buffy coat isolated from a large blood volume than using whole blood for this molecular monitoring.

  20. Venous waterfalls in coronary circulation.

    PubMed

    Gosselin, R E; Kaplow, S M

    1991-03-21

    Several studies of flow through collapsible tubing deformed by external pressures have led to a concept known as the "vascular waterfall". One hallmark of this state is a positive zero-flow pressure intercept (Pe) in flow-pressure curves. This intercept is commonly observed in the coronary circulation, but in blood-perfused beating hearts a vascular waterfall is not the only putative cause. To restrict the possibilities, we have measured flow-pressure curves in excised non-beating rabbit hearts in which the coronary arteries were perfused in a non-pulsatile way with a newtonian fluid (Ringers solution) containing potent vasodilator drugs. Under these circumstances, vascular waterfalls are believed to be the only tenable explanation for Pe. In physical terms the waterfall is a region where the vessel is in a state of partial collapse with a stabilized intraluminal fluid pressure (Pw). It is argued that the most probable site of this collapse was the intramural veins just before they reached the epicardial surface. In accord with the waterfall hypothesis, Pe increased as the heart became more edematous, but flow-pressure curves also became flatter, implying multiple waterfalls with differing Pws, leading to complete collapse of some of the venous channels. The principal compressive force is believed to have been the interstitial fluid pressure as registered through a needle (Pn) implanted in the left ventricular wall, but a small additional force (Ps) was probably due to swelling of interstitial gels. A method is presented for estimating Ps and Pw. Unlike rubber tubing, blood vessels are both collapsible and porous. Apparently because of increased capillary filtration, Pn was found to increase linearly with the perfusion pressure. Thus, Pw was not the same at all points on the flow-pressure curve. This finding has interesting implications with respect to the concept of coronary resistance. PMID:2062096