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Sample records for promoting blood circulation

  1. [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.

  2. [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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Effect of acupoint catgut embedding therapy combined with Chinese medicine for nourishing the kidneys and promoting blood circulation and improving blood glucose and lipid levels as well as the pregnancy rate in obese PCOS patients with infertility

    PubMed Central

    Qin, Wenmin; Zhao, Kai; Yang, Haiyan

    2016-01-01

    In this study, we explored the effect of acupoint catgut embedding combined with Chinese medicine for nourishing kidney and promoting blood circulation as well as improving the glucose and lipid levels and pregnancy rate in obese polycystic ovary syndrome (PCOS) patients with infertility. A total of 62 obese patients with PCOS were randomly divided into three groups, 21 of whom were treated with acupoint catgut embedding combined with Chinese medicine, another 21 with catgut embedding therapy, and 20 only with Chinese medicine. We compared the improvement of clinical symptoms and the glucose and lipid levels in the three groups three months after surgery. We found that the effective rate of obesity treatment, body mass index and waist-to-hip ratio of acupuncture-drug group and catgut embedding group were significantly lower than those of the Chinese medicine group (P<0.05). A comparison between the acupuncture-drug group and catgut embedding group was not statistically significant (P>0.05). The triglyceride (TG) and high-density lipoprotein cholesterol (HDL) levels of the three groups were significantly decreased and increased, respectively, following treatment, with the total cholesterol (TC) level being decreased significantly only in the acupuncture-drug group (P<0.05), and the LDL level showing no significant difference (P>0.05). The fast insulins, HOMA-IR, TG, TC levels and periodic cancellation rate of the acupuncture-drug group was significantly reduced compared to those of the catgut embedding group and Chinese medicine group after treatment, whereas the HDL levels, periodic ovulation rate and clinical pregnancy rate were higher (P<0.05). However, a comparison between Chinese medicine group and catgut embedding group was not statistically significant (P>0.05). The incidence rate of luteinized unruptured follicle and ovarian hyper-stimulation syndrome of the three groups showed no statistical difference (P>0.05). In conclusion, the study has shown that

  10. [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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. [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.

  16. 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.

  17. 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…

  18. 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.

  19. [Blood circulation of cauda equina and nerve root].

    PubMed

    Kobayashi, Shigeru; Baba, Hisatoshi; Uchida, Kenzo; Kokubo, Yasuo; Yayama, Takafumi; Takeno, Kenichi; Negoro, Kohei

    2005-03-01

    It is generally considered that the genesis of radiculopathy associated with pathologic conditions of the spine, such as lumbar disc herniaton and lumbarl canal stenosis, may result from both mechanical compression and vascular problems. In this article, we have reviewed about the blood circulation of cauda equina and nerve root under normal and pathologic conditions.

  20. Origins of circulating endothelial cells and endothelial outgrowth from blood

    PubMed Central

    Lin, Yi; Weisdorf, Daniel J.; Solovey, Anna; Hebbel, Robert P.

    2000-01-01

    Normal adults have a small number of circulating endothelial cells (CEC) in peripheral blood, and endothelial outgrowth has been observed from cultures of blood. In this study we seek insight into the origins of CEC and endothelial outgrowth from cultures of blood. Fluorescence in situ hybridization analysis of blood samples from bone marrow transplant recipients who had received gender-mismatched transplants 5–20 months earlier showed that most CEC in fresh blood had recipient genotype. Endothelial outgrowth from the same blood samples after 9 days in culture (5-fold expansion) was still predominantly of the recipient genotype. In contrast, endothelial outgrowth after ∼1 month (102-fold expansion) was mostly of donor genotype. Thus, recipient-genotype endothelial cells expanded only ∼20-fold over this period, whereas donor-genotype endothelial cells expanded ∼1000-fold. These data suggest that most CEC in fresh blood originate from vessel walls and have limited growth capability. Conversely, the data indicate that outgrowth of endothelial cells from cultures of blood is mostly derived from transplantable marrow-derived cells. Because these cells have more delayed outgrowth but a greater proliferative rate, our data suggest that they are derived from circulating angioblasts. PMID:10619863

  1. 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

  2. Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

    PubMed Central

    Wood, Katherine C.; Cortese-Krott, Miriam M.; Kovacic, Jason C.; Noguchi, Audrey; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Boehm, Manfred; Kato, Gregory J.; Kelm, Malte; Gladwin, Mark T.

    2013-01-01

    Objective Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. While the current paradigm holds that this bioactivity derives specifically from expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted WT and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate L-Arginine, and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-Arginine into 14C-Citrulline in a NOS-dependent fashion. Conclusions These are the first studies to definitively establish a role for a blood borne eNOS, using cross transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect. PMID:23702660

  3. Blood circulation in the ascidian tunicate Corella inflata (Corellidae)

    PubMed Central

    2016-01-01

    The body of the ascidian tunicate Corella inflata is relatively transparent. Thus, the circulatory system can be visualized by injecting high molecular weight fluorescein labeled dextran into the heart or the large vessels at the ends of the heart without surgery to remove the body wall. In addition, after staining with neutral red, the movement of blood cells can be easily followed to further characterize the circulatory system. The heart is two gently curved concentric tubes extending across the width of the animal. The inner myocardial tube has a partial constriction approximately in the middle. As in other tunicates, the heart is peristaltic and periodically reverses direction. During the branchial phase blood leaves the anterior end of the heart by two asymmetric vessels that connect to the two sides of the branchial basket. Blood then flows in both transverse directions through a complex system of ducts in the basket into large ventral and dorsal vessels which carry blood back to the visceral organs in the posterior of the animal. During the visceral phase blood leaves the posterior end of the heart in two vessels that repeatedly bifurcate and fan into the stomach and gonads. Blood velocity, determined by following individual cells in video frames, is high and pulsatory near the heart. A double peak in velocity at the maximum may be due to the constriction in the middle of the heart tube. Blood velocity progressively decreases with distance from the heart. In peripheral regions with vessels of small diameter blood cells frequently collide with vessel walls and cell motion is erratic. The estimated volume of blood flow during each directional phase is greater than the total volume of the animal. Circulating blood cells are confined to vessels or ducts in the visible parts of the animal and retention of high molecular weight dextran in the vessels is comparable to that seen in vertebrates. These are characteristics of a closed circulatory system. PMID:27994977

  4. Blood circulation in the ascidian tunicate Corella inflata (Corellidae).

    PubMed

    Konrad, Michael W

    2016-01-01

    The body of the ascidian tunicate Corella inflata is relatively transparent. Thus, the circulatory system can be visualized by injecting high molecular weight fluorescein labeled dextran into the heart or the large vessels at the ends of the heart without surgery to remove the body wall. In addition, after staining with neutral red, the movement of blood cells can be easily followed to further characterize the circulatory system. The heart is two gently curved concentric tubes extending across the width of the animal. The inner myocardial tube has a partial constriction approximately in the middle. As in other tunicates, the heart is peristaltic and periodically reverses direction. During the branchial phase blood leaves the anterior end of the heart by two asymmetric vessels that connect to the two sides of the branchial basket. Blood then flows in both transverse directions through a complex system of ducts in the basket into large ventral and dorsal vessels which carry blood back to the visceral organs in the posterior of the animal. During the visceral phase blood leaves the posterior end of the heart in two vessels that repeatedly bifurcate and fan into the stomach and gonads. Blood velocity, determined by following individual cells in video frames, is high and pulsatory near the heart. A double peak in velocity at the maximum may be due to the constriction in the middle of the heart tube. Blood velocity progressively decreases with distance from the heart. In peripheral regions with vessels of small diameter blood cells frequently collide with vessel walls and cell motion is erratic. The estimated volume of blood flow during each directional phase is greater than the total volume of the animal. Circulating blood cells are confined to vessels or ducts in the visible parts of the animal and retention of high molecular weight dextran in the vessels is comparable to that seen in vertebrates. These are characteristics of a closed circulatory system.

  5. 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.

  6. Circulating blood volume determination using electronic spin resonance spectroscopy.

    PubMed

    Facorro, Graciela; Bianchin, Ana; Boccio, José; Hager, Alfredo

    2006-09-01

    There have been numerous methods proposed to measure the circulating blood volume (CBV). Nevertheless, none of them have been massively and routinely accepted in clinical diagnosis. This study describes a simple and rapid method, on a rabbit model, using the dilution of autologous red cells labeled with a nitroxide radical (Iodoacetamide-TEMPO), which can be detected by electronic spin resonance (ESR) spectroscopy. Blood samples were withdrawn and re-injected using the ears' marginal veins. The average CBV measured by the new method/body weight (CBV(IAT)/BW) was 59 +/- 7 mL/kg (n = 33). Simultaneously, blood volume determinations using the nitroxide radical and (51)Cr (CBV(Cr)) were performed. In the plot of the difference between the methods (CBV(IAT) - CBV(Cr)) against the average (CBV(IAT) + CBV(Cr))/2, the mean of the bias was -1.1 +/- 6.9 mL and the limits of agreement (mean difference +/-2 SD) were -14.9 and 12.7 mL. Lin's concordance correlation coefficient p(c) = 0.988. Thus, both methods are in close agreement. The development of a new method that allows a correct estimation of the CBV without using radioactivity, avoiding blood manipulation, and decreasing the possibility of blood contamination with similar accuracy and precision of that of the "gold standard method" is an innovative proposal.

  7. [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.

  8. 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'…

  9. Prolonged blood circulation of methotrexate by modulation of liposomal composition.

    PubMed

    Hong, M S; Lim, S J; Lee, M K; Kim, Y B; Kim, C K

    2001-01-01

    Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmacokinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX.

  10. Do circulating blood cells contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period?

    PubMed

    Fujiwara, Hiroshi

    2009-06-01

    In early pregnancy, human chorionic gonadotrophin (HCG) stimulates the corpus luteum (CL) of pregnancy to produce progesterone, which in turn maintains human embryo implantation in the uterus. In addition to this embryo-maternal cross-talk via the endocrine systems through blood circulation, accumulating evidence suggests that circulating blood cells also play an important role in embryo implantation. Peripheral blood mononuclear cells (PBMC) derived from pregnant women increased the progesterone production by luteal cells and promoted the invasion of embryos in vitro. Recombinant-HCG increased chemokine production by PBMC through lectin-glycan interaction and enhanced the effects of PBMC on embryo invasion. Later, it was shown that not only PBMC, but also circulating platelets were possible sources of these chemokines that promote extravillous trophoblast invasion to reconstruct maternal endometrial artery. Circulating platelets were also proposed to induce neovascularization during CL formation. Furthermore, intrauterine administration of autologous PBMC effectively improved live birth, pregnancy and implantation rates in patients with repeated (four or more) implantation failures during in vitro fertilization therapy. These findings suggest that circulating blood cells positively contribute to maternal tissue remodeling and embryo-maternal cross-talk around the implantation period in cooperation with the endocrine system.

  11. 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.

  12. Nanostructured Substrates for Capturing Circulating Tumor Cells in Whole Blood

    NASA Astrophysics Data System (ADS)

    Tseng, Hsian-Rong

    2009-03-01

    Over the past decade, circulating tumor cells (CTCs) has become an emerging ``biomarker'' for detecting early-stage cancer metastasis, predicting patient prognosis, as well as monitoring disease progression and therapeutic outcomes. However, isolation of CTCs has been technically challenging due to the extremely low abundance (a few to hundreds per ml) of CTCs among a high number of hematologic cells (109 per mL) in the blood. Our joint research team at UCLA has developed a new cell capture technology for quantification of CTCs in whole blood samples. Similar to most of the existing approaches, epithelial cell adhesion molecule antibody (anti-EpCAM) was grafted onto the surfaces to distinguish CTCs from the surrounding hematologic cells. The uniqueness of our technology is the use of nanostructured surfaces, which facilitates local topographical interactions between CTCs and substrates at the very first cell/substrate contacting time point. We demonstrated the ability of these nanostructured substrates to capture CTCs in whole blood samples with significantly improved efficiency and selectivity. The successful demonstration of this cell capture technology using brain, breast and prostate cancer cell lines encouraged us to test this approach in clinical setting. We have been able to bond our first validation study with a commercialized technology based on the use of immunomagnetic nanoparticles. A group of clinically well-characterized prostate cancer patients at UCLA hospital have been recruited and tested in parallel by these two technologies.

  13. [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

  14. [The analysis of tincture for improvement of blood circulation].

    PubMed

    Bernatoniene, Rūta; Bernatoniene, Jurga; Ramanauskiene, Kristina

    2004-01-01

    The article describes qualitative and quantitative analysis of tincture for improvement of blood circulation. Flavonoids have been qualitatively determined by methods of thin-layer chromatography, high-pressure liquid chromatography and color reaction with magnesium powder and concentrated hydrochloric acid. Ferments were identified with ferric ammonium sulphate solution; glycosides--with dimethylaminobenzaldehyde solution in sulphur acid; saponin--with lead subacetate solution; reductive materials - with silver nitrate ammoniacal solution; albumen--with ninhydrin solution; and caffeic acid--by method of thin-layer chromatography. An optimal spectrophotometrical method for determining the quantity of quercetin was applied. The refractive index, relative density, loss of drying and ethanol concentration were determined according to European Pharmacopoeia Requirements.

  15. [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".

  16. Renalase Lowers Ambulatory Blood Pressure by Metabolizing Circulating Adrenaline

    PubMed Central

    Desir, Gary V.; Tang, LieQi; Wang, Peili; Li, Guoyong; Sampaio‐Maia, Benedita; Quelhas‐Santos, Janete; Pestana, Manuel; Velazquez, Heino

    2012-01-01

    Background Blood pressure is acutely regulated by the sympathetic nervous system through the action of vasoactive hormones such as epinephrine, norepinephrine, and dopamine. Renalase, a recently described, secreted flavoprotein, acutely decreases systemic pressure when administered in vivo. Single‐nucleotide polymorphisms present in the gene are associated with hypertension, cardiac disease, and diabetes. Although renalase's crystal structure was recently solved, its natural substrate(s) remains undefined. Methods and Results Using in vitro enzymatic assays and in vivo administration of recombinant renalase, we show that the protein functions as a flavin adenine dinucleotide– and nicotinamide adenine dinucleotide–dependent oxidase that lowers blood pressure by degrading plasma epinephrine. The enzyme also metabolizes the dopamine precursor l‐3,4‐dihydroxyphenylalanine but has low activity against dopamine and does not metabolize norepinephrine. To test if epinephrine and l‐3,4‐dihydroxyphenylalanine were renalase's only substrates, 17 246 unique small molecules were screened. Although the search revealed no additional, naturally occurring compounds, it identified dobutamine, isoproterenol, and α‐methyldopa as substrates of renalase. Mutational analysis was used to test if renalase's hypotensive effect correlated with its enzymatic activity. Single–amino acid mutations that decrease its enzymatic activity to varying degrees comparably reduce its hypotensive effect. Conclusions Renalase metabolizes circulating epinephrine and l‐3,4‐dihydroxyphenylalanine, and its capacity to decrease blood pressure is directly correlated to its enzymatic activity. These findings highlight a previously unrecognized mechanism for epinephrine metabolism and blood pressure regulation, expand our understanding of the sympathetic nervous system, and could lead to the development of novel therapeutic modalities for the treatment of hypertension. (J Am Heart Assoc

  17. [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.

  18. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation.

    PubMed

    Uhrin, Pavel; Zaujec, Jan; Breuss, Johannes M; Olcaydu, Damla; Chrenek, Peter; Stockinger, Hannes; Fuertbauer, Elke; Moser, Markus; Haiko, Paula; Fässler, Reinhard; Alitalo, Kari; Binder, Bernd R; Kerjaschki, Dontscho

    2010-05-13

    During embryonic development, lymph sacs form from the cardinal vein, and sprout centrifugally to form mature lymphatic networks. Separation of the lymphatic from the blood circulation by a hitherto unknown mechanism is essential for the homeostatic function of the lymphatic system. O-glycans on the lymphatic endothelium have recently been suggested to be required for establishment and maintenance of distinct blood and lymphatic systems, primarily by mediating proper function of podoplanin. Here, we show that this separation process critically involves platelet activation by podoplanin. We found that platelet aggregates build up in wild-type embryos at the separation zone of podoplanin(+) lymph sacs and cardinal veins, but not in podoplanin(-/-) embryos. Thus, podoplanin(-/-) mice develop a "nonseparation" phenotype, characterized by a blood-filled lymphatic network after approximately embryonic day 13.5, which, however, partially resolves in postnatal mice. The same embryonic phenotype is also induced by treatment of pregnant mice with acetyl salicylic acid, podoplanin-blocking antibodies, or by inactivation of the kindlin-3 gene required for platelet aggregation. Therefore, interaction of endothelial podoplanin of the developing lymph sac with circulating platelets from the cardinal vein is critical for separating the lymphatic from the blood vascular system.

  19. 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)

  20. Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells

    PubMed Central

    Terai, Mizue; Mu, Zhaomei; Eschelman, David J.; Gonsalves, Carin F.; Kageyama, Ken; Chervoneva, Inna; Orloff, Marlana; Weight, Ryan; Mastrangelo, Michael J.; Cristofanilli, Massimo; Sato, Takami

    2015-01-01

    Background CTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients. Methods Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements. Finding CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases. Interpretation Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs. PMID:26870807

  1. 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.

  2. [Cord blood circulating endothelial progenitors: perspectives for clinical use in cardiovascular diseases].

    PubMed

    Uzan, Georges; Vanneaux, Valérie; Delmau, Catherine; Ayoubi, Fida; Gluckman, Eliane; Larghero, Jérôme

    2009-03-01

    The discovery of circulating endothelial progenitor cells (EPCs) in adult peripheral blood has opened up many exciting possibilities in vascular biology. Several studies have confirmed the existence of EPCs, as well as their bone marrow origin and their ability to integrate into vascular structures at sites of neoangiogenesis. EPCs appear to be naturally involved in the prevention of ischemia by participating directly in the vascularization process. Given their tropism for sites of neoangiogenesis, EPCs have clear therapeutic potential for treating ischemic diseases. If associated with other cell therapy products, they could improve tissue regeneration by promoting graft vascularization. However, the use of EPCs as a cell therapy product is limited by their rarity in peripheral blood. Cord blood contains many more EPCs, which are functional and can be expanded in culture. Their clinical use will require expansion in strictly controlled conditions and rigorous validation in preclinical models. EPCs could also serve as a quality markerforfrozen cord blood, showing the presence of non hematopoietic stem cells.

  3. Differential uptake of grepafloxacin by human circulating blood neutrophils and those exudated into tissues.

    PubMed

    Niwa, M; Hotta, K; Kanamori, Y; Matsuno, H; Kozawa, O; Hirota, M; Uematsu, T

    2001-09-28

    The uptake of the antimicrobial quinolone agent, grepafloxacin, both by human circulating blood neutrophils and by those exudated into tissues, was evaluated in vitro by comparing the intracellular drug concentrations. In circulating blood neutrophils, the uptake of grepafloxacin was rapid and saturable at 37 degrees C. The uptake of grepafloxacin into circulating blood neutrophils was reduced by lowering the environmental temperature or by the presence of metabolic inhibitors, suggesting the involvement of an active transport mechanism. Furthermore, the uptake of grepafloxacin by tissue (salivary) neutrophils was also partially temperature-dependent and was significantly greater than that by circulating blood neutrophils, i.e. exudation of neutrophils into tissue results in a markedly enhanced transport mechanism for grepafloxacin. This phenomenon may be related to the higher defense activity against infection seen in exudated tissue neutrophils.

  4. Potential donor segregation to promote blood donation.

    PubMed

    Martín-Santana, Josefa D; Beerli-Palacio, Asunción

    2008-04-01

    This work is set in the field of social marketing and more specifically in the context of blood donation. Its principal objective focuses on segregating potential donors by using the inhibitors or barriers to a blood donation behaviour as criteria. Moreover, an analysis of the predisposition to donate blood, the intrinsic and extrinsic motivations for donating blood, and the incentives that may stimulate their donation conduct was conducted for each of the four identified groups. The results reveal that the four segments differ significantly in their predisposition to donate, in their motivations and in the incentives that encourage them to donate blood.

  5. New data on the process of circulation and blood oxygenation in the lungs under physiological conditions.

    PubMed

    Ivanov, K P

    2013-02-01

    Blood flow through the human lungs weighing 600 g is about 5 to 6 liters per minute. Blood capacity of human lung is about 500 ml. Therefore, 500 ml blood is oxygenated for 5 sec. Questions arise how such a large volume of blood passes through such a small mass of the lungs and what causes very rapid blood oxygenation. Since the structure of the lungs in mammals is almost the same, the work was carried out on rats (in rats 20-22 ml of blood per minute passes through the lungs weighing 1.5-2.0 g). Intensive blood circulation was proved to be linked with a large diameter pulmonary arterioles and high blood flow velocity in them. The oxygenation rate is explained by special structure of the alveoli and special blood flow conditions, which creates ideal conditions for oxygen diffusion.

  6. Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells

    PubMed Central

    de Wolski, Karen; Fu, Xiaoyoun; Dumont, Larry J.; Roback, John D.; Waterman, Hayley; Odem-Davis, Katherine; Howie, Heather L.; Zimring, James C.

    2016-01-01

    Transfusion of red blood cells is a very common inpatient procedure, with more than 1 in 70 people in the USA receiving a red blood cell transfusion annually. However, stored red blood cells are a non-uniform product, based upon donor-to-donor variation in red blood cell storage biology. While thousands of biological parameters change in red blood cells over storage, it has remained unclear which changes correlate with function of the red blood cells, as opposed to being co-incidental changes. In the current report, a murine model of red blood cell storage/transfusion is applied across 13 genetically distinct mouse strains and combined with high resolution metabolomics to identify metabolic changes that correlated with red blood cell circulation post storage. Oxidation in general, and peroxidation of lipids in particular, emerged as changes that correlated with extreme statistical significance, including generation of dicarboxylic acids and monohydroxy fatty acids. In addition, differences in anti-oxidant pathways known to regulate oxidative stress on lipid membranes were identified. Finally, metabolites were identified that differed at the time the blood was harvested, and predict how the red blood cells perform after storage, allowing the potential to screen donors at time of collection. Together, these findings map out a new landscape in understanding metabolic changes during red blood cell storage as they relate to red blood cell circulation. PMID:26921359

  7. Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells.

    PubMed

    de Wolski, Karen; Fu, Xiaoyoun; Dumont, Larry J; Roback, John D; Waterman, Hayley; Odem-Davis, Katherine; Howie, Heather L; Zimring, James C

    2016-05-01

    Transfusion of red blood cells is a very common inpatient procedure, with more than 1 in 70 people in the USA receiving a red blood cell transfusion annually. However, stored red blood cells are a non-uniform product, based upon donor-to-donor variation in red blood cell storage biology. While thousands of biological parameters change in red blood cells over storage, it has remained unclear which changes correlate with function of the red blood cells, as opposed to being co-incidental changes. In the current report, a murine model of red blood cell storage/transfusion is applied across 13 genetically distinct mouse strains and combined with high resolution metabolomics to identify metabolic changes that correlated with red blood cell circulation post storage. Oxidation in general, and peroxidation of lipids in particular, emerged as changes that correlated with extreme statistical significance, including generation of dicarboxylic acids and monohydroxy fatty acids. In addition, differences in anti-oxidant pathways known to regulate oxidative stress on lipid membranes were identified. Finally, metabolites were identified that differed at the time the blood was harvested, and predict how the red blood cells perform after storage, allowing the potential to screen donors at time of collection. Together, these findings map out a new landscape in understanding metabolic changes during red blood cell storage as they relate to red blood cell circulation.

  8. [The reaction of the pulpal blood circulation to thermal stimuli].

    PubMed

    Gängler, P

    1976-01-01

    The present paper characterizes the reactions of the systemcirculation and microcirculation of the pulpa to the effects of temperature changes from--30 degrees C to +55 degrees C. In the range between 25 degrees C and 50 degrees C an increase of the blood flow rate can be observed. By long-standing action of temperatures above 40 degrees C and below 25 degrees C a dilatation of the blood vessels and a decrease of the blood flow rate are caused, thus leading to aggregations, capillary stoppage, and finally to thrombosis of entire pulpa sections. In addition to the outline of the critical initial alterations of the microcirculation in the course of inflammation the clinical conclusions towards crown and cavity preparation by means of water spray cooling, concerning thermal sensibility tests, and cryo-surgical operations are discussed.

  9. 3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood.

    PubMed

    Zheng, Siyang; Lin, Henry K; Lu, Bo; Williams, Anthony; Datar, Ram; Cote, Richard J; Tai, Yu-Chong

    2011-02-01

    Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.

  10. 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.

  11. 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

  12. [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.

  13. 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

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

    PubMed

    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

    2016-04-19

    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.

  15. 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…

  16. Fast multi-spectral imaging technique for detection of circulating endothelial cells in human blood samples

    NASA Astrophysics Data System (ADS)

    Berezhnyy, Ihor V.; Berezhna, Svitlana Y.

    2012-08-01

    The appearance of non-blood cells circulating in human peripheral bloodstream indicates an abnormal condition. One important category of these cells is circulating endothelial cells (CECs) shed by compromised blood vessels. Clinical applications that measure the blood level of CECs are hindered due to a lack of standardized instruments. The major challenge in detecting circulating non-blood cells is their extreme scarcity; 1 in 106 to 107. Described here is a new method for detection of rare cells in blood samples deposited on the adhesive microscopic slides and immunostained with distinct fluorescent markers. The key novelty of the proposed approach is an intelligent search principle and a dual-mode scanner to implement this principle. To begin, a fast scanning that uses a single beam is performed in the spectral channel where only rare cells produce florescence. Once a target cell is registered, the scanner switches on the imaging mode, auto-focuses and then records images in multiple spectral channels at the selected area. The instrument runs in repetitive cycles until the entire slide is scanned. The technology has been validated via detection of human umbilical vein endothelial cells spiked into human blood samples. In addition, the operational principle can be adapted for detection of other types of rare cells in blood.

  17. [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.

  18. 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.

  19. Device to determine the level of peripheral blood circulation and saturation

    NASA Astrophysics Data System (ADS)

    Kozlovska, Tetyana I.; Sander, Sergii V.; Zlepko, Sergii M.; Vasilenko, Valentina B.; Pavlov, Volodymyr S.; Dumenko, Victoria P.; Klapouschak, Andrii Yu.; Maciejewski, Marcin; DzierŻak, RóŻa; Surtel, Wojciech

    2016-09-01

    The paper evaluated the diagnostic value of laser photoplethysmography when examining patients with chronic lower limb ischemia. A statistical analysis of the research results was made, and diagrams of relationship between the degrees of ischemia and blood flow are presented. Development of the device to determine the level of peripheral blood circulation and saturation was presented. Also additional accessories in the form of optical fibers for different applications were suggested.

  20. The history of the theory of the circulation of the blood.

    PubMed

    Rampling, M W

    2016-01-01

    An obvious candidate for the seminal event in the history of haemorheology is Harvey's presentation of the concept of the circulation of the blood. Prior to this, the ideas concerning the movement of blood were based, in Europe and Middle East, largely on the principles laid down by Galen, and these had been, in effect, dogma for nearly a millennium and a half. These principles were basically that blood is formed in the liver, thence it travels to the bodily organs and is consumed -hence there is one-way flow and no circulation of the blood at all. Harvey's revolutionary idea that blood circulates repeatedly around the cardiovascular system laid the foundation for haemorheology because once that idea was accepted then the fluidity of the blood immediately became potentially of crucial importance - and haemorheology was conceived. In this paper the ideas that preceded Harvey will be presented, i.e. those of Galen, Ibn al-Nafis, Vesalius, Fabricius and Colombo etc. Harvey's awareness of this background, due mainly to time spent in Padua, triggered his many experimental investigations and discoveries. Ultimately, these led to his astonishing insights published in De Mortu Cordis in 1628 which changed the understanding of the cardio-vascular system forever.

  1. A rapid, automated surface protein profiling of single circulating exosomes in human blood

    PubMed Central

    Kibria, Golam; Ramos, Erika K.; Lee, Katelyn E.; Bedoyan, Sarah; Huang, Simo; Samaeekia, Ravand; Athman, Jaffre J.; Harding, Clifford V.; Lötvall, Jan; Harris, Lyndsay; Thompson, Cheryl L.; Liu, Huiping

    2016-01-01

    Circulating exosomes provide a promising approach to assess novel and dynamic biomarkers in human disease, due to their stability, accessibility and representation of molecules from source cells. However, this potential has been stymied by lack of approaches for molecular profiling of individual exosomes, which have a diameter of 30–150 nm. Here we report a rapid analysis approach to evaluate heterogeneous surface protein expression in single circulating exosomes from human blood. Our studies show a differential CD47 expression in blood-derived individual circulating exosomes that is correlated with breast cancer status, demonstrating a great potential of individual exosome profiles in biomarker discovery. The sensitive and high throughput platform of single exosome analysis can also be applied to characterizing exosomes derived from other patient fluids. PMID:27819324

  2. Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation

    SciTech Connect

    Molloy, Janelle A.

    2010-11-15

    Purpose: Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these ''sequential'' techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Methods: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than {+-}10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times

  3. 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…

  4. [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.

  5. 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

  6. [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.

  7. 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

  8. Requirement of vasculogenesis and blood circulation in late stages of liver growth in zebrafish

    PubMed Central

    Korzh, Svetlana; Pan, Xiufang; Garcia-Lecea, Marta; Winata, Cecilia Lanny; Pan, Xiaotao; Wohland, Thorsten; Korzh, Vladimir; Gong, Zhiyuan

    2008-01-01

    Background Early events in vertebrate liver development have been the major focus in previous studies, however, late events of liver organogenesis remain poorly understood. Liver vasculogenesis in vertebrates occurs through the interaction of endoderm-derived liver epithelium and mesoderm-derived endothelial cells (ECs). In zebrafish, although it has been found that ECs are not required for liver budding, how and when the spatio-temporal pattern of liver growth is coordinated with ECs remains to be elucidated. Results To study the process of liver development and vasculogenesis in vivo, a two-color transgenic zebrafish line Tg(lfabf:dsRed; elaA:EGFP) was generated and named LiPan for liver-specific expression of DsRed RFP and exocrine pancreas-specific expression of GFP. Using the LiPan line, we first followed the dynamic development of liver from live embryos to adult and showed the formation of three distinct yet connected liver lobes during development. The LiPan line was then crossed with Tg(fli1:EGFP)y1 and vascular development in the liver was traced in vivo. Liver vasculogenesis started at 55–58 hpf when ECs first surrounded hepatocytes from the liver bud surface and then invaded the liver to form sinusoids and later the vascular network. Using a novel non-invasive and label-free fluorescence correction spectroscopy, we detected blood circulation in the liver starting at ~72 hpf. To analyze the roles of ECs and blood circulation in liver development, both cloche mutants (lacking ECs) and Tnnt2 morphants (no blood circulation) were employed. We found that until 70 hpf liver growth and morphogenesis depended on ECs and nascent sinusoids. After 72 hpf, a functional sinusoidal network was essential for continued liver growth. An absence of blood circulation in Tnnt2 morphants caused defects in liver vasculature and small liver. Conclusion There are two phases of liver development in zebrafish, budding and growth. In the growth phase, there are three distinct

  9. 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.

  10. A strategy to identify genes associated with circulating solid tumor cell survival in peripheral blood.

    PubMed Central

    Fournier, M. V.; Carvalho, M. G.; Pardee, A. B.

    1999-01-01

    Efforts in metastasis research have centered on the phenotypic and genetic differences between primary site and metastatic site tumors. However, genes that may be used as molecular markers of metastasis in circulating tumor cells remain unidentified. Genes regulating the dissemination and survival of solid tumor cells in the blood, as well as their adaptation to new environments, could be candidates for unique metastatic tumor markers. Differential display (DD) was conducted to compare the blood of tumor-free individuals with the blood of patients with lung, breast, and colon cancers. Twenty-one up-expressed genes in the tumor patient blood samples but none in the tumor-free donor blood samples were identified. Nine of these samples were isolated, amplified, and directly sequenced. A gene AB-1 homologous to a Bcl-2 family member, which might function as an apoptosis inhibitor, was identified. The overexpression of an apoptosis inhibitor in blood from patients with metastatic tumors might be correlated with the capability of solid tumor cells to survive in peripheral blood. This is the first demonstration of the usefulness of comparing control and patient blood samples by DD to find novel potential genetic markers identifying metastasis in the blood. http://link.springer-ny. com/link/service/journals/00020/bibs/5n5p313.html Images Fig. 1 Fig. 2 Fig. 3 PMID:10390547

  11. Health Promotion to Reduce Blood Pressure Level among Older Blacks.

    ERIC Educational Resources Information Center

    Haber, David

    1986-01-01

    Low-income Black elders completed a 10-week health promotion program for the purpose of lowering or stabilizing blood pressure levels. Comparisons were made between classes that met weekly versus three times a week, and between yoga and aerobics formats. A peer-led program was developed that continued for 10 months after the professionally-led…

  12. 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.

  13. Optical aggregometry of red blood cells associated with the blood-clotting reaction in extracorporeal circulation support.

    PubMed

    Sakota, Daisuke; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu

    2016-09-01

    The aggregability of red blood cell (RBCs) is associated with the contribution of plasma proteins, such as fibrinogen and lipoproteids, to blood-clotting. Hence, we hypothesized that RBC aggregability reflects the blood-clotting reaction. A noninvasive optical monitoring method to measure RBC aggregability for the assessment of blood-clotting stage during mechanical circulatory support was developed. An in vitro thrombogenic test was conducted with a rotary blood pump using heparinized fresh porcine blood. Near-infrared laser light at a wavelength of 785 nm was guided by an optical fiber. The fibers for detecting incident, forward-, and backward-scattered light were fixed on the circuit tubing with an inner diameter of 1/4 inch. Because there is substantial RBC aggregation at low shear flow rates, a pulsatile flow was generated by controlling the pump rotational speed. The flow rate was changed from 0 to 8.5 L/min at a period of 40 s. The intensities of forward- and backward-scattered light changed dramatically when the flow stopped. The aggregability was evaluated by the increase ratio of the transmitted light intensity from the flow stopping in the low-flow condition. The experiment started when the anticoagulation was stopped by the addition of protamine into the circulating blood. Reduction in RBC aggregability was associated with a decrease in the amount of fibrinogen and the number of platelets. Continuous, noninvasive monitoring of thrombosis risk is possible using optical measurements combining pulsatile flow control of a rotary blood pump. RBC aggregometry is a potential label-free method for evaluating blood-clotting risk.

  14. 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.

  15. 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

  16. Effect of a deproteinized blood extract on the recovery of blood circulation in an ischaemic skin lesion.

    PubMed Central

    Smahel, J.

    1982-01-01

    An experimental model was used to study the revascularization of an ischaemic skin lesion and the effect on this process of the blood extract Solcoseryl. Under the conditions given in the experiment, restoration of the circulation was by 2 modes--re-flow in the original vessels, and neovascularization. Solcoseryl given daily i.p. encouraged the re-flow phenomenon and therefore, by improving the microcirculation and nutrition, the healing of the ischaemic lesions. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:6176254

  17. 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).

  18. 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.

  19. 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.

  20. Circulating Aneuploid Cells Detected in the Blood of Patients with Infectious Lung Diseases

    PubMed Central

    Kim, Hongsun; Cho, Jong Ho; Sonn, Chung-Hee; Kim, Jae-Won; Choi, Yul; Lee, Jinseon; Kim, Jhingook

    2017-01-01

    The identification of circulating tumor cells (CTCs) is clinically important for diagnosing cancer. We have previously developed a size-based filtration platform followed by epithelial cell adhesion molecule immunofluorescence staining for detecting CTCs. To characterize CTCs independently of cell surface protein expression, we incorporated a chromosomal fluorescence in situ hybridization (FISH) assay to detect abnormal copy numbers of chromosomes in cells collected from peripheral blood samples by the size-based filtration platform. Aneuploid cells were detected in the peripheral blood of patients with lung cancer. Unexpectedly, aneuploid cells were also detected in the control group, which consisted of peripheral blood samples from patients with benign lung diseases, such as empyema necessitatis and non-tuberculous mycobacterial lung disease. These findings suggest that chromosomal abnormalities are observed not only in tumor cells, but also in benign infectious diseases. Thus, our findings present new considerations and bring into light the possibility of false positives when using FISH for cancer diagnosis. PMID:28382274

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients via RT-qPCR

    PubMed Central

    Andergassen, Ulrich; Kölbl, Alexandra C.; Hutter, Stefan; Friese, Klaus; Jeschke, Udo

    2013-01-01

    Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment. PMID:24202442

  6. The Role of Circulating Tight Junction Proteins in Evaluating Blood Brain Barrier Disruption following Intracranial Hemorrhage.

    PubMed

    Jiao, Xiaoyang; He, Ping; Li, Yazhen; Fan, Zhicheng; Si, Mengya; Xie, Qingdong; Chang, Xiaolan; Huang, Dongyang

    2015-01-01

    Brain injury after intracranial hemorrhage (ICH) results in significant morbidity and mortality. Blood brain barrier (BBB) disruption is a hallmark of ICH-induced brain injury; however, data mirroring BBB disruption in human ICH are scarce. The aim of this study was to assess the significance of circulating biomarkers in evaluating BBB disruption after ICH. Twenty-two patients with ICH were recruited in this study. Concentrations of the tight junction proteins (TJs) Claudin-5 (CLDN5), Occludin (OCLN), and zonula occludens 1 (ZO-1) and vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were measured by using enzyme-linked immunosorbent assay in serum and cerebrospinal fluid (CSF) samples obtained from patients with ICH. The white blood cell (WBC) count in blood and CSF, albumin (ALB) levels in the CSF (ALBCSF), and the BBB ratio were significantly higher in the ICH than in controls (p < 0.05). Significantly higher levels of CLDN5, OCLN, ZO-1, MMP-9, and VEGF in CSF were observed in the ICH group; these biomarkers were also positively associated with BBB ratio (p < 0.05). Our data revealed that circulating TJs could be considered the potential biomarkers reflecting the integrity of the BBB in ICH.

  7. The Role of Circulating Tight Junction Proteins in Evaluating Blood Brain Barrier Disruption following Intracranial Hemorrhage

    PubMed Central

    Jiao, Xiaoyang; He, Ping; Li, Yazhen; Fan, Zhicheng; Si, Mengya; Xie, Qingdong; Chang, Xiaolan; Huang, Dongyang

    2015-01-01

    Brain injury after intracranial hemorrhage (ICH) results in significant morbidity and mortality. Blood brain barrier (BBB) disruption is a hallmark of ICH-induced brain injury; however, data mirroring BBB disruption in human ICH are scarce. The aim of this study was to assess the significance of circulating biomarkers in evaluating BBB disruption after ICH. Twenty-two patients with ICH were recruited in this study. Concentrations of the tight junction proteins (TJs) Claudin-5 (CLDN5), Occludin (OCLN), and zonula occludens 1 (ZO-1) and vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were measured by using enzyme-linked immunosorbent assay in serum and cerebrospinal fluid (CSF) samples obtained from patients with ICH. The white blood cell (WBC) count in blood and CSF, albumin (ALB) levels in the CSF (ALBCSF), and the BBB ratio were significantly higher in the ICH than in controls (p < 0.05). Significantly higher levels of CLDN5, OCLN, ZO-1, MMP-9, and VEGF in CSF were observed in the ICH group; these biomarkers were also positively associated with BBB ratio (p < 0.05). Our data revealed that circulating TJs could be considered the potential biomarkers reflecting the integrity of the BBB in ICH. PMID:26586924

  8. Highly sensitive transient absorption imaging of graphene and graphene oxide in living cells and circulating blood.

    PubMed

    Li, Junjie; Zhang, Weixia; Chung, Ting-Fung; Slipchenko, Mikhail N; Chen, Yong P; Cheng, Ji-Xin; Yang, Chen

    2015-07-23

    We report a transient absorption (TA) imaging method for fast visualization and quantitative layer analysis of graphene and GO. Forward and backward imaging of graphene on various substrates under ambient condition was imaged with a speed of 2 μs per pixel. The TA intensity linearly increased with the layer number of graphene. Real-time TA imaging of GO in vitro with capability of quantitative analysis of intracellular concentration and ex vivo in circulating blood were demonstrated. These results suggest that TA microscopy is a valid tool for the study of graphene based materials.

  9. [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.

  10. The role of circulating mesenchymal progenitor cells, fibrocytes, in promoting pulmonary fibrosis.

    PubMed

    Strieter, Robert M; Keeley, Ellen C; Burdick, Marie D; Mehrad, Borna

    2009-01-01

    The resident fibroblast has been traditionally viewed as the primary cell involved in promoting pulmonary fibrosis. However, contemporary findings now support the concept of a circulating cell (fibrocyte) that also contributes to pulmonary fibrosis. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of cell surface markers related to leukocytes, hematopoietic progenitor cells and fibroblasts. Fibrocytes are unique in that they are capable of differentiating into fibroblasts and myofibroblasts, as well as adipocytes. In this review, we present data supporting the critical role these cells play in the pathogenesis of pulmonary fibrosis.

  11. 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

  12. Optical properties of circulating human blood in the wavelength range 400-2500 nm

    NASA Astrophysics Data System (ADS)

    Roggan, Andre; Friebel, Moritz; Doerschel, Klaus; Hahn, Andreas; Mueller, Gerhard J.

    1999-01-01

    Knowledge about the optical properties (mu) a, (mu) s, and g of human blood plays an important role for many diagnostic and therapeutic applications in laser medicine and medical diagnostics. They strongly depend on physiological parameters such as oxygen saturation, osmolarity, flow conditions, haematocrit, etc. The integrating sphere technique and inverse Monte Carlo simulations were applied to measure (mu) a, (mu) s, and g of circulating human blood. At 633 nm the optical properties of human blood with a haematocrit of 10% and an oxygen saturation of 98% were found to be 0.210 +/- 0.002 mm-1 for (mu) a, 77.3 +/- 0.5 mm-1 for (mu) s, and 0.994 +/- 0.001 for the g factor. An increase of the haematocrit up to 50% lead to a linear increase of absorption and reduced scattering. Variations in osmolarity and wall shear rate led to changes of all three parameters while variations in the oxygen saturation only led to a significant change of the absorption coefficient. A spectrum of all three parameters was measured in the wavelength range 400 - 2500 nm for oxygenated and deoxygenated blood, showing that blood absorption followed the absorption behavior of haemoglobin and water. The scattering coefficient decreased for wavelengths above 500 nm with approximately (lambda) -1.7; the g factor was higher than 0.9 over the whole wavelength range.

  13. 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.

  14. [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.

  15. Increased Blood Pressure Variability Is Associated with Worse Neurologic Outcome in Acute Anterior Circulation Ischemic Stroke

    PubMed Central

    Bennett, Alicia; Stoddard, Gregory J.; Smith, Gordon; Wang, Haimei; Wold, Jana; Chung, Lee; Tirschwell, David L.; Majersik, Jennifer J.

    2016-01-01

    Background. Although research suggests that blood pressure variability (BPV) is detrimental in the weeks to months after acute ischemic stroke, it has not been adequately studied in the acute setting. Methods. We reviewed acute ischemic stroke patients from 2007 to 2014 with anterior circulation stroke. Mean blood pressure and three BPV indices (standard deviation, coefficient of variation, and successive variation) for the intervals 0–24, 0–72, and 0–120 hours after admission were correlated with follow-up modified Rankin Scale (mRS) in ordinal logistic regression models. The correlation between BPV and mRS was further analyzed by terciles of clinically informative stratifications. Results. Two hundred and fifteen patients met inclusion criteria. At all time intervals, increased systolic BPV was associated with higher mRS, but the relationship was not significant for diastolic BPV or mean blood pressure. This association was strongest in patients with proximal stroke parent artery vessel occlusion and lower mean blood pressure. Conclusion. Increased early systolic BPV is associated with worse neurologic outcome after ischemic stroke. This association is strongest in patients with lower mean blood pressure and proximal vessel occlusion, often despite endovascular or thrombolytic therapy. This hypothesis-generating dataset suggests potential benefit for interventions aimed at reducing BPV in this patient population. PMID:27974991

  16. 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.

  17. 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. PMID:27626049

  18. 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.

  19. [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.

  20. Development of a new control device for stabilizing blood level in reservoir during extracorporeal circulation.

    PubMed

    Momose, Naoki; Yamakoshi, Rie; Kokubo, Ryo; Yasuda, Toru; Iwamoto, Norio; Umeda, Chinori; Nakajima, Itsuro; Yanagisawa, Mitsunobu; Tomizawa, Yasuko

    2010-03-01

    We developed a simple device that stabilizes the blood level in the reservoir of the extracorporeal circulation open circuit system by measuring the hydrostatic pressure of the reservoir to control the flow rate of the arterial pump. When the flow rate of the venous return decreases, the rotation speed of the arterial pump is automatically slowed down. Consequently, the blood level in the reservoir is stabilized quickly between two arbitrarily set levels and never falls below the pre-set low level. We conducted a basic experiment to verify the operation of the device, using a mock circuit with water. Commercially available pumps and reservoir were used without modification. The results confirmed that the control method effectively regulates the reservoir liquid level and is highly reliable. The device possibly also functions as a safety device.

  1. 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.

  2. 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.

  3. 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

  4. [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.

  5. 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

    2009-04-08

    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.

  6. 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.

  7. Aptamers Selected to Postoperative Lung Adenocarcinoma Detect Circulating Tumor Cells in Human Blood

    PubMed Central

    Zamay, Galina S; Kolovskaya, Olga S; Zamay, Tatiana N; Glazyrin, Yury E; Krat, Alexey V; Zubkova, Olga; Spivak, Ekaterina; Wehbe, Mohammed; Gargaun, Ana; Muharemagic, Darija; Komarova, Mariia; Grigorieva, Valentina; Savchenko, Andrey; Modestov, Andrey A; Berezovski, Maxim V; Zamay, Anna S

    2015-01-01

    Circulating tumor cells (CTCs) are rare cells and valuable clinical markers of prognosis of metastasis formation and prediction of patient survival. Most CTC analyses are based on the antibody-based detection of a few epithelial markers; therefore miss an important portion of mesenchymal cancer cells circulating in blood. In this work, we selected and identified DNA aptamers as specific affinity probes that bind to lung adenocarcinoma cells derived from postoperative tissues. The unique feature of our selection strategy is that aptamers are produced for lung cancer cell biomarkers in their native state and conformation without previous knowledge of the biomarkers. The aptamers did not bind to normal lung cells and lymphocytes, and had very low affinity to A549 lung adenocarcinoma culture. We applied these aptamers to detect CTCs, apoptotic bodies, and microemboli in clinical samples of peripheral blood of lung cancer and metastatic lung cancer patients. We identified aptamer-associated protein biomarkers for lung cancer such as vimentin, annexin A2, annexin A5, histone 2B, neutrophil defensin, and clusterin. Tumor-specific aptamers can be produced for individual patients and synthesized many times during anticancer therapy, thereby opening up the possibility of personalized diagnostics. PMID:26061649

  8. Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

    PubMed Central

    Gabizon, A; Papahadjopoulos, D

    1988-01-01

    The rapid clearance of circulating liposomes from the bloodstream, coupled with their high uptake by liver and spleen, has thus far been an obstacle to any attempts at targeting to tumors. We have assessed the impact of liposome composition on their clearance from the circulation in normal and tumor-bearing mice and on their uptake by tumors and various normal tissues. By selective changes in lipid composition, while maintaining a mean particle diameter of approximately equal to 100 nm, we have achieved up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. injection. Concomitantly, there was a decrease by a factor of 4 of the recovered dose localizing in the liver and spleen, the major organs of the reticuloendothelial system. Parallel experiments in tumor-bearing mice demonstrated a 25-fold increase of the liposome concentration in the tumor when formulations with long and short blood residence time were compared. The most favorable results were obtained with liposomes containing a small molar fraction of a negatively charged glycolipid, such as monosialoganglioside or phosphatidylinositol, and a solid-phase neutral phospholipid as the bulk component. The bio-distribution of such formulations is of considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizing the likelihood of toxicity to the reticuloendothelial system. PMID:3413128

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

    PubMed

    Jiang, Chunling; Qian, Hong; Luo, Shuhua; Lin, Jing; Yu, Jerry; Li, Yajiao; An, Qi; Luo, Nanfu; Du, Lei

    2017-05-01

    Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 μg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 μg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

  14. 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

  15. Umbilical Cord Blood Circulating Progenitor Cells and Endothelial Colony-Forming Cells Are Decreased in Preeclampsia.

    PubMed

    Gumina, Diane L; Black, Claudine P; Balasubramaniam, Vivek; Winn, Virginia D; Baker, Christopher D

    2016-01-01

    Preeclampsia (PE) is a pregnancy-specific disease characterized by the new onset of hypertension and proteinuria. Mothers with PE are known to develop endothelial dysfunction, but its effect on infants has been understudied, as newborns are often asymptomatic. Recent studies indicate that infants born from preeclamptic pregnancies develop endothelial dysfunction including higher blood pressure during childhood and an increased risk of stroke later in life. We hypothesize that PE reduces the number and function of fetal angiogenic progenitor cells and may contribute to this increased risk. We quantified 2 distinct types of angiogenic progenitors, pro-angiogenic circulating progenitor cells (CPCs) and endothelial colony-forming cells (ECFCs), from the umbilical cord blood of preeclamptic pregnancies and normotensive controls. Pro-angiogenic and nonangiogenic CPCs were enumerated via flow cytometry and ECFCs by cell culture. Additionally, we studied the growth, migration, and tube formation of ECFCs from PE and gestational age-matched normotensive control pregnancies. We found that PE resulted in decreased cord blood pro-angiogenic CPCs and ECFCs. Nonangiogenic CPCs were also decreased. Preeclamptic ECFCs demonstrated decreased growth and migration but formed tube-like structures in vitro similar to controls. Our results suggest that the preeclamptic environment alters the number and function of angiogenic progenitor cells and may increase the risk of later vascular disease.

  16. A compact centrifugal blood pump for extracorporeal circulation: design and performance.

    PubMed

    Tanaka, S; Yamamoto, S; Yamakoshi, K; Kamiya, A

    1987-08-01

    A new compact centrifugal blood pump driven by a miniature DC servomotor has been designed for use for short-term extra corporeal and cardiac-assisted circulation. The impeller of the pump was connected directly to the motor by using a simple-gear coupling. The shaft for the impeller was sealed from blood by both a V-ring and a seal bearing. Either pulsatile or nonpusatile flow was produced by controlling the current supply to the motor. The pump characteristics and the degree of hemolysis were evaluated with regard to the configuration of the impeller with a 38-mm outer diameter in vitro tests; the impeller having the blade angles at the inlet of 20 deg and at the outlet of 50 deg was the most appropriate as a blood pump. The performance in an operation, hemolysis and thrombus formation in the pump were assessed by a left ventricular bypass experiment in dogs. It was suggested by this study that this prototype pump appears promising for use not only in animal experiments but also in clinical application.

  17. Gravity, blood circulation, and the adaptation of form and function in lower vertebrates.

    PubMed

    Lillywhite, H B

    Gravitational force influences musculoskeletal systems, fluid distribution, and hydrodynamics of the circulation, especially in larger terrestrial vertebrates. The disturbance to hydrodynamics and distribution of body fluids relates largely to the effects of hydrostatic pressure gradients acting in vertical blood columns. These, in turn, are linked to the evolution of adaptive countermeasures involving modifications of structure and function. Comparative studies of snakes suggest there are four generalizations concerning adaptive countermeasures to gravity stress that seem relevant to lower vertebrates generally. First, increasing levels of regulated arterial blood pressure are expected to evolve with some relation to gravitational stresses incurred by the effects of height and posture on vertical blood columns above the heart. Second, aspects of gross anatomical organization are expected to evolve in relation to gravitational influence incurred by habitat and behavior. Third, natural selection coupled to gravitational stresses has favored morphological features that reduce the compliance of perivascular tissues and provide an anatomical "antigravity suit." Fourth, natural selection has produced gradients or regional differences of vascular characteristics in tall or elongated vertebrates that are active in high gravity stress environments. Consideration or awareness of these principles should be incorporated into interpretations of structure and function in lower vertebrates.

  18. The promotion of endothelial progenitor cells recruitment by nerve growth factors in tissue-engineered blood vessels.

    PubMed

    Zeng, Wen; Yuan, Wei; Li, Li; Mi, Jianhong; Xu, Shangcheng; Wen, Can; Zhou, Zhenhua; Xiong, Jiaqiang; Sun, Jiansen; Ying, Dajun; Yang, Mingcan; Li, Xiaosong; Zhu, Chuhong

    2010-03-01

    Endothelial progenitor cells (EPCs) mobilization and homing are critical to the development of an anti-thrombosis and anti-stenosis tissue-engineered blood vessel. The growth and activation of blood vessels are supported by nerves. We investigated whether nerve growth factors (NGF) can promote EPCs mobilization and endothelialization of tissue-engineered blood vessels. In vitro, NGF promoted EPCs to form more colonies, stimulated human EPCs to differentiate into endothelial cells, and significantly enhanced EPCs migration. Flow cytometric analysis revealed that NGF treatment increased the number of EPCs in the peripheral circulation of C57BL/6 mice. Furthermore, the treatment of human EPCs with NGF facilitated their homing into wire-injured carotid arteries after injection into mice. Decellularized rat blood vessel matrix was incubated with EDC cross-linked collagen and bound to NGF protein using the bifunctional coupling agent N-succinmidyl3-(2-pyridyldit-hio) propionate (SPDP). The NGF-bound tissue-engineered blood vessel was implanted into rat carotid artery for 1 week and 1 month. NGF-bound blood vessels possessed significantly higher levels of endothelialization and patency than controls did. These results demonstrated that NGF can markedly increase EPCs mobilization and homing to vascular grafts. Neurotrophic factors such as NGF have a therapeutic potential for the construction of tissue-engineered blood vessels in vivo.

  19. ALLERGIC PULMONARY INFLAMMATION PROMOTES THE RECRUITMENT OF CIRCULATING TUMOR CELLS TO THE LUNG

    PubMed Central

    Taranova, Anna G.; Maldonado, David; Vachon, Celine M.; Jacobsen, Elizabeth A.; Abdala-Valencia, Hiam; McGarry, Michael P.; Ochkur, Sergei I.; Protheroe, Cheryl A.; Doyle, Alfred; Grant, Clive S.; Cook-Mills, Joan; Birnbaumer, Lutz; Lee, Nancy A.; Lee, James J.

    2010-01-01

    Allergen-induced respiratory inflammation facilitates and/or elicits the extravasation of proinflammatory leukocytes by well understood mechanisms that mediate the movement of multiple cell types. The non-specific character of these pathways led us to hypothesize that circulating cancer cells use similar mechanisms, promoting secondary tumor formation at distal sites. To test this hypothesis, the frequency of metastasis to the lung as a function of allergic pulmonary inflammation was assessed following the intravenous injection of B16-F10 melanoma cells in mice. These studies demonstrated that allergen-induced pulmonary inflammation resulted in a >3-fold increase in lung metastases. This increase was dependent on CD4+ T cell activities; however, it occurred independent of the induced eosinophilia associated with allergen provocation. Interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the enhanced pulmonary recruitment of cancer cells from circulation. Additional mechanistic studies further suggested that the ability of circulating cancer cells to extravasate to surrounding lung tissues was linked to the activation of the vascular endothelium via one or more Gαi-coupled receptors. Interestingly, a survey of a clinical breast cancer surgical database showed that the incidence of asthma was higher among patients with lung metastases. Thus, our data demonstrate that allergic respiratory inflammation may represent a risk factor for the development of lung metastases and suggests that amelioration of the pulmonary inflammation associated with asthma will have a direct and immediate benefit to the 7–8% of breast cancer patients with this lung disease. PMID:18922934

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

    PubMed Central

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

    2014-01-01

    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 and coworkers (Ottesen et al., 2003; Olufsen et al., 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 ≥ 50µm. 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 of circulatory diseases within the lung. PMID:24610385

  1. Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes

    PubMed Central

    Fujisawa, Takeshi; Wang, Keqing; Niu, Xi-Lin; Egginton, Stuart; Ahmad, Shakil; Hewett, Peter; Kontos, Christopher D.; Ahmed, Asif

    2017-01-01

    Aims Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse. Methods and results Apo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced. Conclusions Ang-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis. PMID:28069704

  2. [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.

  3. Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo.

    PubMed

    Nissinen, Tuomo; Näkki, Simo; Laakso, Hanne; Kučiauskas, Dalius; Kaupinis, Algirdas; Kettunen, Mikko I; Liimatainen, Timo; Hyvönen, Mervi; Valius, Mindaugas; Gröhn, Olli; Lehto, Vesa-Pekka

    2016-12-07

    Drug carrier systems based on mesoporous inorganic nanoparticles generally face the problem of fast clearance from bloodstream thus failing in passive and active targeting to cancer tissue. To address this problem, a specific dual PEGylation (DPEG) method for mesoporous silicon (PSi) was developed and studied in vitro and in vivo. The DPEG coating changed significantly the behavior of the nanoparticles in vivo, increasing the circulation half-life from 1 to 241 min. Furthermore, accumulation of the coated particles was mainly taking place in the spleen whereas uncoated nanoparticles were rapidly deposited in the liver. The protein coronas of the particles differed considerably from each other. The uncoated particles had substantially more proteins adsorbed including liver and immune active proteins, whereas the coated particles had proteins capable of suppressing cellular uptake. These reasons along with agglomeration observed in blood circulation were concluded to cause the differences in the behavior in vivo. The biofate of the particles was monitored with magnetic resonance imaging by incorporating superparamagnetic iron oxide nanocrystals inside the pores of the particles making dynamic imaging of the particles feasible. The results of the present study pave the way for further development of the porous inorganic delivery system in the sense of active targeting as the carriers can be easily chemically modified allowing also magnetically targeted delivery and diagnostics.

  4. [The dynamics of blood circulation in marginal gingiva after crown preparation by different ledge locations].

    PubMed

    Shcherbakov, A S; Kuznetsova, M B; Kuznetsov, D L; Ivanova, S B

    2013-01-01

    The periodontal tissue level may change after gingival margin retraction and tooth preparation. The aim of the study was to assess the influence of these manipulations on the condition of free gingival margin. The study included 53 persons (29 women and 24 men) divided into 4 groups followed-up for 6 to 8 weeks. Blood circulation in marginal gingiva of 118 teeth with healthy periodontal tissues was assessed by ultrasonic Doppler evaluation to reveal the circulation impairments in cervical margin after teeth crown preparation. The first group included 39 teeth, in which the gum was retracted by Roeko stay put non impregna cords ("Langenau", Germany). The second group included 39 teeth with shoulders prepared at the gingival margin; in the third group (40 teeth) the shoulder was located subgingivally. The fourth group (40 teeth) was control. The changes in recovery indices have been analyzed. The linear values were established as most significant and demonstrative. The indices variations and recovery period length depended on the coronal edge location. Statistically significant differences were found among all the groups (p>0.05). The results may be used to improve crown preparation for fixed dentures and decrease the recession rate of free gingival margin.

  5. [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.

  6. [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.

  7. Effects of Therapeutic Ultrasound on Intramuscular Blood Circulation and Oxygen Dynamics

    PubMed Central

    Karasuno, Hiroshi; Yokoi, Yuka; Morozumi, Kazunori; Ogihara, Hisayoshi; Ito, Toshikazu; Fujiwara, Takayuki; Fujimoto, Tetsuya; Abe, Koji

    2014-01-01

    Purpose: This study aimed to clarify the effects of therapeutic ultrasound on intramuscular local blood circulation (and oxygen dynamics) using near-infrared spectroscopy (NIRS). Participants: The participants were 11 healthy males. Methods: All participants performed all three trials; (1) the ultrasound (US group), (2) without powered ultrasound (placebo group), and (3) rest (control group). Ultrasound was applied at 3 MHz, 1.0 W/cm2, and 100% duty cycle for 10 minutes. Evaluation index were oxygenated, deoxygenated, and total hemoglobin (Hb) concentrations in the intramuscular and skin surface temperature (SST). The experimental protocol was a total of 40 minutes, that is, 10 minutes before trial (rest), 10 minutes during the trial (ultrasound, placebo, and control), and 20 minutes after trial (rest). The NIRS and SST data collected before and after the trial were divided into 5 minutes intervals for further analysis. Results: Oxygenated and total hemoglobin levels were significantly higher in the US group than in the placebo and control groups for the 20 minutes after ultrasound (p < 0.01). The SST was significantly higher in the US group than in the control for 15 minutes after ultrasound (p < 0.05), while it was significantly lower in the placebo group than in the US and control groups for 20 minutes after the trials (p < 0.01). Conclusion: The effects of ultrasound were maintained for 20 minutes after the trial on intramuscular blood circulation and oxygen dynamics. These effects were caused by a combination of thermal and mechanical effects of the ultrasound. PMID:25792902

  8. Administration of Traditional Chinese Blood Circulation Activating Drugs for Microvascular Complications in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    He, Lisha; Wang, Han; Gu, Chengjuan; He, Xinhui

    2016-01-01

    Traditional Chinese medicine (TCM) is an important complementary strategy for treating diabetes mellitus (DM) in China. Traditional Chinese blood circulation activating drugs are intended to guide an overall approach to the prevention and treatment of microvascular complications of DM. The core mechanism is related to the protection of the vascular endothelium and the basement membrane. Here, we reviewed the scientific evidence underpinning the use of blood circulation activating drugs to prevent and treat DM-induced microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR). Furthermore, we summarized the effects and mechanism of TCM on improving blood rheology, inhibiting aggregation of platelet, forming advanced glycation end products (AGEs), regulating oxidative stress, reducing blood fat, and improving lipid metabolism. The paper provides a new theoretical basis for the clinical practice of TCM in the prevention and treatment of DM and its microvascular complications. PMID:27830156

  9. 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

  10. 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.

  11. 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

  12. Separation of breast cancer cells from peripherally circulating blood using antibodies fixed in microchannels

    NASA Astrophysics Data System (ADS)

    Feng, Juan; Soper, Steven A.; McCarley, Robin L.; Murphy, Michael C.

    2004-07-01

    Bio-Micro Electro Mechanical System (Bio-MEMS) technology was applied to the problem of early breast cancer detection and diagnosis. A micro-device is being developed to identify and specifically collect tumor cells of low abundance (1 tumor cell among 107 normal blood cells) from circulating whole blood. By immobilizing anti-EpCAM (Epithelial Cell Adhesion Molecule) antibodies on polymer micro-channel walls by chemically modifying the surface of the PMMA, breast cancer cells from the MCF-7 cell line, which over-express EpCAM, were selected from a sample volume by the strong binding affinity between the antibody and antigen. To validate the capture of the breast cancer cells, three fluorochrome markers, each identified by a separate color, were used to reliably identify the cancer cells. The cancer cells were defined by DAPI+ (blue), CD45- and the FITC-cell membrane linker+ (green). White blood cells, which may interfere in the detection of the cancer cells, were identified by DAPI+ (blue), CD45+ (red), and the FITC-cell membrane linker+ (green). EpCAM/anti-EpCAM binding models from the literature were used to estimate an optimal velocity, 2mm/sec, for maximizing the number of cells binding and the critical binding force. At higher velocities, shear forces (> 0.48 dyne) will break existing bonds and prevent the formation of new ones. This detection micro-device can be assembled with other lab-on-a-chip components for follow-up gene and protein analysis.

  13. 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...

  14. 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.…

  15. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans

    PubMed Central

    Gladwin, Mark T.; Shelhamer, James H.; Schechter, Alan N.; Pease-Fye, Margaret E.; Waclawiw, Myron A.; Panza, Julio A.; Ognibene, Frederick P.; Cannon, Richard O.

    2000-01-01

    To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso-albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and S-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress. PMID:11027349

  16. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans.

    PubMed

    Gladwin, M T; Shelhamer, J H; Schechter, A N; Pease-Fye, M E; Waclawiw, M A; Panza, J A; Ognibene, F P; Cannon, R O

    2000-10-10

    To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso-albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and S-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress.

  17. Stability of Circulating Blood-Based MicroRNAs – Pre-Analytic Methodological Considerations

    PubMed Central

    Boddum, Kim; Jabbari, Reza; Jabbari, Javad; Risgaard, Bjarke; Tomsits, Philipp; Hildebrand, Bianca; Kääb, Stefan; Wakili, Reza; Jespersen, Thomas; Tfelt-Hansen, Jacob

    2017-01-01

    Background and aim The potential of microRNAs (miRNA) as non-invasive diagnostic, prognostic, and predictive biomarkers, as well as therapeutic targets, has recently been recognized. Previous studies have highlighted the importance of consistency in the methodology used, but to our knowledge, no study has described the methodology of sample preparation and storage systematically with respect to miRNAs as blood biomarkers. The aim of this study was to investigate the stability of miRNAs in blood under various relevant clinical and research conditions: different collection tubes, storage at different temperatures, physical disturbance, as well as serial freeze-thaw cycles. Methods Blood samples were collected from 12 healthy donors into different collection tubes containing anticoagulants, including EDTA, citrate and lithium-heparin, as well as into serum collection tubes. MiRNA stability was evaluated by measuring expression changes of miR-1, miR-21 and miR-29b at different conditions: varying processing time of whole blood (up to 72 hours (h)), long-term storage (9 months at -80°C), physical disturbance (1 and 8 h), as well as in a series of freeze/thaw cycles (1 and 4 times). Results Different collection tubes revealed comparable concentrations of miR-1, miR-21 and miR-29b. Tubes with lithium-heparin were found unsuitable for miRNA quantification. MiRNA levels were stable for at least 24 h at room temperature in whole blood, while separated fractions did show alterations within 24 h. There were significant changes in the miR-21 and miR-29b levels after 72 h incubation of whole blood at room temperature (p<0.01 for both). Both miR-1 and miR-21 showed decreased levels after physical disturbance for 8 h in separated plasma and miR-1 in serum whole blood, while after 1 h of disturbance no changes were observed. Storage of samples at -80°C extended the miRNA stability remarkably, however, miRNA levels in long-term stored (9 months) whole blood samples were

  18. Circulating tumor cell is a common property of brain glioma and promotes the monitoring system

    PubMed Central

    Gao, Faliang; Cui, Yong; Jiang, Haihui; Sui, Dali; Wang, Yonggang; Jiang, Zhongli; Zhao, Jizong; Lin, Song

    2016-01-01

    Brain glioma is the most common primary intracranial tumor characterized by dismal prognosis and frequent recurrence, yet a real-time and reliable biological approach to monitor tumor response and progression is still lacking. Recently, few studies have reported that circulating tumor cells (CTCs) could be detected in glioblastoma multiform (GBM), providing the possibility of its application in brain glioma monitoring system. But its application limits still exist, because the detection rate of CTCs is still low and was exclusively limited to high- grade gliomas. Here, we adopted an advanced integrated cellular and molecular approach of SE-iFISH to detect CTCs in the peripheral blood (PB) of patients with 7 different subtypes of brain glioma, uncovering the direct evidences of glioma migration. We identified CTCs in the PB from 24 of 31 (77%) patients with glioma in all 7 subtypes. No statistical difference of CTC incidence and count was observed in different pathological subtypes or WHO grades of glioma. Clinical data revealed that CTCs, to some extent, was superior to MRI in monitoring the treatment response and differentiating radionecrosis from recurrence of glioma. Conclusively, CTCs is a common property of brain gliomas of various pathological subtypes, which has provided an ultimate paradox for the hypothesis “soil and seed”. It can be used to monitor the microenvironment of gliomas dynamically, which will be a meaningful complement to radiographic imaging. PMID:27517490

  19. Patient-specific computational modeling of blood flow in the pulmonary arterial circulation.

    PubMed

    Kheyfets, Vitaly O; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J; Finol, Ender A

    2015-07-01

    Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right Heart Catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R(2)=0.77, P<0.05) and arterial compliance (C) (R(2)=0.63, P<0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained

  20. Patient-Specific Computational Modeling of Blood Flow in the Pulmonary Arterial Circulation

    PubMed Central

    Kheyfets, Vitaly O.; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J.; Finol, Ender A.

    2015-01-01

    Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right heart catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear Stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R2 = 0.77, P < 0.05) and arterial compliance (C) (R2 = 0.63, P < 0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained

  1. 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.

  2. 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.

  3. A new rotary blood pump for versatile extracorporeal circulation: the DeltaStream.

    PubMed

    Göbel, C; Arvand, A; Rau, G; Reul, H; Meyns, B; Flameng, W; Eilers, R; Marseille, O

    2002-09-01

    Today, rotary pumps are routinely used for extracorporeal circulation in different clinical settings and applications. A review of these applications and specific limitations in extracorporeal perfusion was performed and served as a basis for the development of the DeltaStream. The DeltaStreams is a miniaturized rotary blood pump of a new and unique design with an integrated drive unit. Despite its small design, the pump maintains a sufficient hydraulic capacity, which makes the DeltaStream very flexible for intra- and perioperative applications. It also opens the field for short-term ventricular assist devices (VAD) applications or use as a component in extracorporeal life support systems (ECLS). The DeltaStream and, specifically, its impeller design have been optimized with respect to haemolysis and nonthrombogenicity. Also, the pump facilitates an effective pulse generation in VAD applications and simulates heart action in a more physiological way than other rotary pumps or roller pumps. Hydraulic and haematological properties have been tested in vitro and in vivo. In a series of seven animal experiments in two different setups, the pump demonstrated its biocompatibility and applicability. Basic aspects of the DeltaStream pump concept as well as important console features are presented. A summary of the final investigation of this pump is given with focus on hydraulic capabilities and results from animal studies.

  4. 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.

  5. 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.

  6. 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.

  7. Circulating microRNAs as stable blood-based markers for cancer detection

    PubMed Central

    Mitchell, Patrick S.; Parkin, Rachael K.; Kroh, Evan M.; Fritz, Brian R.; Wyman, Stacia K.; Pogosova-Agadjanyan, Era L.; Peterson, Amelia; Noteboom, Jennifer; O'Briant, Kathy C.; Allen, April; Lin, Daniel W.; Urban, Nicole; Drescher, Charles W.; Knudsen, Beatrice S.; Stirewalt, Derek L.; Gentleman, Robert; Vessella, Robert L.; Nelson, Peter S.; Martin, Daniel B.; Tewari, Muneesh

    2008-01-01

    Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small (≈22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer. PMID:18663219

  8. Circulating microRNAs as stable blood-based markers for cancer detection.

    PubMed

    Mitchell, Patrick S; Parkin, Rachael K; Kroh, Evan M; Fritz, Brian R; Wyman, Stacia K; Pogosova-Agadjanyan, Era L; Peterson, Amelia; Noteboom, Jennifer; O'Briant, Kathy C; Allen, April; Lin, Daniel W; Urban, Nicole; Drescher, Charles W; Knudsen, Beatrice S; Stirewalt, Derek L; Gentleman, Robert; Vessella, Robert L; Nelson, Peter S; Martin, Daniel B; Tewari, Muneesh

    2008-07-29

    Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small ( approximately 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.

  9. 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

  10. 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.

  11. Elevated circulating CD14(low)CD16(+) monocyte subset in primary biliary cirrhosis correlates with liver injury and promotes Th1 polarization.

    PubMed

    Peng, Anping; Ke, Peifeng; Zhao, Rong; Lu, Xinyi; Zhang, Cheng; Huang, Xianzhang; Tian, Guangjun; Huang, Jun; Wang, Jinli; Invernizzi, Pietro; Chen, Qubo; Zhuang, Junhua

    2016-11-01

    Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease in which monocytes/macrophages infiltration and skewed T helper type (Th) 1 and Th17 cell responses participate in the development of the disease. Human peripheral blood monocytes are heterogeneous and can be divided into classical CD14(high)CD16(-), intermediate CD14(high)CD16(+), and nonclassical CD14(low)CD16(+) monocyte subsets. Compared to classical monocytes, CD16(+) monocytes are generally termed pro-inflammatory monocytes and play an important pathogenic role in autoimmune diseases. However, little is known about the immunophenotype and immunopathogenic role of peripheral blood CD16(+) monocytes in PBC. Thus, we investigated the phenotype and function of these circulating monocyte subsets from PBC patients. The frequencies of circulating CD14(high)CD16(+) and CD14(low)CD16(+) subpopulation were increased in disease compared with healthy controls. Among them, CD14(low)CD16(+) monocyte subset positively correlated with disease progress, liver damage indicators and serum C-reactive protein, respectively. Furthermore, the frequencies of Th1 and Th17 cells were upregulated and CD14(low)CD16(+) monocyte subset was also positively associated with Th1 cell frequency in PBC. Using a vitro coculture model, we further found that CD14(low)CD16(+) monocytes promoted Th1 cell polarization compared to classical monocytes. Interleukin-12 (IL-12) and direct contact of patient CD4(+)T cell and CD14(low)CD16(+) monocytes, were responsible for CD14(low)CD16(+) monocytes promotion of Th1 cells polarization in PBC. Our study demonstrated that the enhanced CD14(low)CD16(+) monocyte subset participated in fostering liver damage and inflammatory responses, and promoted Th1 cells skewing in PBC.

  12. [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.

  13. Enrichment of circulating tumor cells in tumor-bearing mouse blood by a deterministic lateral displacement microfluidic device.

    PubMed

    Okano, Hiromasa; Konishi, Tomoki; Suzuki, Toshihiro; Suzuki, Takahiro; Ariyasu, Shinya; Aoki, Shin; Abe, Ryo; Hayase, Masanori

    2015-01-01

    Concentration of real tumor cells leaking into blood from cancer was attempted by a deterministic lateral displacement (DLD) microfluidic device. Spiked cultured cell line tumor cells are often used to verify performance of the circulating tumor cells (CTCs) separation methods. Cultured tumor cells are obviously larger than most of hematocytes and considered not to be appropriate as CTC mimics, while there is uncertainty in identifying real CTCs from clinical samples and there is no practical way to examine CTCs leakage into benign cells during the sorting. In this work, blood samples were prepared from tumor-bearing mice whose tumors were induced by implanting cells with GFP expression to living mice. Therefore, CTCs were identified by their fluorescence emission. We succeeded in the enrichment of tumor cells to 0.05% from the blood, in which CTCs were negligibly detected among three million blood cells, and little loss of CTCs was observed.

  14. High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension.

    PubMed

    de Haro Moraes, C; Figueiredo, V N; de Faria, A P C; Barbaro, N R; Sabbatini, A R; Quinaglia, T; Ferreira-Melo, S E; Martins, L C; Demacq, C; Júnior, H M

    2013-04-01

    Leptin and aldosterone have been associated with the pathophysiological mechanisms of hypertension. However, despite studies showing the association of leptin with intima-media thickness, arterial distensibility and sympathetic nerve activation, the relationship between leptin and blood pressure (BP) in resistant hypertension (RHTN) is unknown. We aimed to assess the correlation of plasma leptin and aldosterone levels with BP in uncontrolled controlled RHTN (UCRHTN) and CRHTN patients. Plasma leptin and aldosterone levels, office BP, ambulatory BP monitoring and heart rate were measured in 41 UCRHTN, 39 CRHTN and 31 well-controlled HTN patients. No differences were observed between the three groups regarding gender, body mass index and age. The UCRHTN group had increased leptin when compared with CRHTN and well-controlled HTN patients (38.2±21.4, 19.6±8.7 and 20.94±13.9 ng ml(-1), respectively; P<0.05). Aldosterone levels values were also statistically different when comparing RHTN, CRHTN and well-controlled HTN patients (9.6±3.8, 8.1±5.0 and 8.0±4.7 ng dl(-1), respectively; P<0.05). As expected, UCRHTN patients had higher heart rate values compared with CRHTN and well-controlled HTN patients (86.2±7.2, 83.5±6.7 and 83.4±8.5, respectively; P<0.05). Plasma leptin positively correlated with systolic (SBP) and diastolic BP (DBP), and aldosterone (r=0.43, 0.35 and 0.47, respectively; all P<0.05) in UCRHTN, but neither in the CRHTN nor in the HTN group. Simple linear regression showed that SBP, DBP and aldosterone may be predicted by leptin (r(2)=0.16, 0.15 and 0.19, respectively; all P<0.05) only in the UCRHTN subgroup. In conclusion, UCRHTN patients have higher circulating leptin levels associated with increased plasma aldosterone and BP levels when compared with CRHTN and HTN subjects.

  15. The Association between Whole Blood Viscosity and Coronary Collateral Circulation in Patients with Chronic Total Occlusion

    PubMed Central

    Ozcan Cetin, Elif Hande; Balcı, Kevser Gülcihan; Aydin, Selahattin; Ediboglu, Emek; Bayraktar, Muhammed Fatih; Balcı, Mustafa Mücahit; Maden, Orhan; Temizhan, Ahmet; Aydogdu, Sinan

    2016-01-01

    Background and Objectives Coronary collateral circulation (CCC) has been attributed as inborn bypass mechanisms supporting ischemic myocardium. Various factors have been postulated in CCC. Whole blood viscosity (WBV) has been an underappreciated entity despite close relationships between multiple cardiovascular diseases. WBV can be calculated with a validated equation from hematocrit and total plasma protein levels for a low and high shear rate. On the grounds, we aimed to evaluate the association between WBV and CCC in patients with chronic total occlusion. Subjects and Methods A total of 371 patients diagnosed as having at least one major, chronic total occluded coronary artery were included. 197 patients with good CCC (Rentrop 2 and 3) composed the patient group. The poor collateral group consisted of 174 patients (Rentrop grade 0 and 1). Results Patients with poor CCC had higher WBV values for a low-shear rate (LSR) (69.5±8.7 vs. 60.1±9.8, p<0.001) and high-shear rate (HSR) (17.0±2.0 vs. 16.4±1.8, p<0.001) than the good collateral group. Correlation analysis demonstrated a significant negative correlation between the grade of CCC and WBV for LSR (β=0.597, p<0.001) and HSR (β=0.494, p<0.001). WBV for LSR (β=0.476, p<0.001) and HSR (β=0.407, p<0.001) had a significant correlation with the synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score. A multivariate analysis showed that the WBV for both shear rates were independent risk factors of poor CCC (WBV at LSR, OR: 1.362 CI 95%: 1.095-1.741 p<0.001 and WBV at HSR, 1.251 CI 95%: 1.180-1.347 p<0.001). Conclusion WBV has been demonstrated as the overlooked predictor of poor coronary collateralization. WBV seemed to be associated with microvascular perfusion and angiogenesis process impairing CCC development. PMID:27826336

  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. Tiny magnetic wireless pump: Fabrication of magnetic impeller and magnetic wireless manipulation for blood circulation in legs

    NASA Astrophysics Data System (ADS)

    Kim, Sung Hoon; Yu, Chang Ho; Ishiyama, K.

    2015-05-01

    This paper introduces a wireless pump that uses magnetic wireless manipulation to pump blood in the legs. A compact size and sufficient hydrodynamic performance were the most important requirements. Because the bonded magnet technique allows for a complex shape and various magnetization orientations, we fabricated a magnetic impeller from magnetic SmFeN powder. The impellers demonstrated a magnetic moment of 2772.64 emu and coercive force of 7.55 kOe. Using the impeller, we developed a tiny blood pump with a diameter of 22 mm and height of 6 mm. The pump allows for a maximum flow rate of 2.7 l/min and maximum pump head of approximately 170 mm Hg at a rotating speed of 6000 rpm. This level of hydrodynamic performance is sufficient to circulate blood in the legs. In this paper, we present the magnetic properties of the magnetic impeller and the hydrodynamic performance with wireless operation.

  18. 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.

  19. Measurement of anterior and posterior circulation flow contributions to cerebral blood flow. An ultrasound-derived volumetric flow analysis.

    PubMed

    Boyajian, R A; Schwend, R B; Wolfe, M M; Bickerton, R E; Otis, S M

    1995-01-01

    Ultrasound-derived volumetric flow analysis may be useful in answering questions of basic physiological interest in the cerebrovascular circulation. Using this technique, the authors have sought to describe quantitatively the complete concurrent flow relations among all four arteries supplying the brain. The aim of this study of normal subjects was to determine the relative flow contributions of the anterior (internal carotid arteries) and posterior (vertebral arteries) cerebral circulation. Comparisons between the observed and theoretically expected anterior and posterior flow distribution would provide an opportunity to assess traditional rheological conceptions in vivo. Pulsed color Doppler ultrasonography was used to measure mean flow rates in the internal carotid and vertebral arteries in 21 normal adults. The anterior circulation (internal carotid arteries bilaterally) carried 82% of the brain's blood supply and comprised 67% of the total vascular cross-sectional area. These values demonstrate precise concordance between observations in vivo and the theoretically derived (Hagen-Poiseuille) expected flow distribution. These cerebrovascular findings support the traditional conception of macroscopic blood flow. Further studies using ultrasound-derived volumetric analysis of the brain's arterial flow relations may illuminate the vascular pathophysiology underlying aging, cerebral ischemia, and dementias.

  20. Potentials of the circulating pruritogenic mediator lysophosphatidic acid in development of allergic skin inflammation in mice: role of blood cell-associated lysophospholipase D activity of autotaxin.

    PubMed

    Shimizu, Yoshibumi; Morikawa, Yoshiyuki; Okudaira, Shinichi; Kimoto, Shigenobu; Tanaka, Tamotsu; Aoki, Junken; Tokumura, Akira

    2014-05-01

    Itching and infiltration of immune cells are important hallmarks of atopic dermatitis (AD). Although various studies have focused on peripheral mediator-mediated mechanisms, systemic mediator-mediated mechanisms are also important in the pathogenesis and development of AD. Herein, we found that intradermal injection of lysophosphatidic acid (LPA), a bioactive phospholipid, induces scratching responses by Institute of Cancer Research mice through LPA1 receptor- and opioid μ receptor-mediating mechanisms, indicating its potential as a pruritogen. The circulating level of LPA in Naruto Research Institute Otsuka Atrichia mice, a systemic AD model, with severe scratching was found to be higher than that of control BALB/c mice, probably because of the increased lysophospholipase D activity of autotaxin (ATX) in the blood (mainly membrane associated) rather than in plasma (soluble). Heparan sulfate proteoglycan was shown to be involved in the association of ATX with blood cells. The sequestration of ATX protein on the blood cells by heparan sulfate proteoglycan may accelerate the transport of LPA to the local apical surface of vascular endothelium with LPA receptors, promoting the hyperpermeability of venules and the pathological uptake of immune cells, aggravating lesion progression and itching in Naruto Research Institute Otsuka Atrichia mice.

  1. Disruption of circulation by ethanol promotes fetal alcohol spectrum disorder (FASD) in medaka (Oryzias latipes) embryogenesis.

    PubMed

    Hu, Yuhui; Khan, Ikhlas A; Dasmahapatra, Asok K

    2008-09-01

    Japanese medaka (Oryzias latipes) embryos exposed to ethanol have developed craniofacial, cardiovascular and skeletal defects which can be compared with the phenotypic features of fetal alcohol spectrum disorder (FASD) observed in human. The present experiment was designed to show that the disruption in circulation by ethanol during embryogenesis is a potential cause of FASD. Fertilized eggs were exposed to ethanol (0, 100 and/or 400 mM) for 24 or 48 h at various developmental stages (Iwamatsu stages 4-30) and were analyzed at 6 day post fertilization (dpf). It was observed that controls and the embryos exposed to 100 mM ethanol were in circulating state; however, a significant number of embryos of stages 4-24 exposed to 400 mM ethanol had disrupted circulation. Compared to controls, protein and RNA contents were significantly reduced in non-circulating embryos. Lipid peroxidation (LPO) analysis was made at 3, 6, 24, 48, 96 and 144 hour post fertilization (hpf). LPO was increased with the advancement of morphogenesis; however, ethanol or the circulation status had no effect. We further analyzed alcohol dehydrogenase (Adh 5 and adh8) and aldehyde dehydrogenase (Aldh9A and Aldh1A2) enzyme mRNAs in the embryos exposed to 400 mM ethanol for 24 h. A developmental stage-specific reduction in these enzyme mRNAs by ethanol was observed. We conclude that ethanol-induced disruption in circulation during embryogenesis is a potential cause of the development of FASD features in medaka.

  2. 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.

  3. 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

  4. Superparamagnetic anisotropic nano-assemblies with longer blood circulation in vivo: a highly efficient drug delivery carrier for leukemia therapy.

    PubMed

    Xiong, Fei; Tian, Jilai; Hu, Ke; Zheng, Xiawen; Sun, Jianfei; Yan, Caiyun; Yao, Juan; Song, Lina; Zhang, Yu; Gu, Ning

    2016-10-06

    Leukemia, unlike solid tumors, has no definite shape and spreads throughout the whole circulatory system, therefore the therapy of leukemia requires medication to stay longer in the circulatory system. Anisotropic nanoparticles, showing longer blood circulating life than that of isotropic nanoparticles reported in previous research, meet the demands of leukemia therapy. Based on this strategy, superparamagnetic anisotropic nano-assemblies (SANs) were fabricated and loaded with vincristine (VCR) to form VCR-SANs. When compared to the same dose of VCR-loaded isotropic nano-assemblies (SINs), the decrease in the leukocytes count and the positive expression ratio of CD13 in the VCR-SANs group were 19.38% and 16.4%, respectively, which indicated the improved anti-leukemia activity of the VCR-SANs. From the results of the pharmacokinetics study, the VCR-SANs remarkably held the amount of drug removed from the whole body per unit time half of the isotropic group and the concentration of drug in blood plasma against time was 2.1 times the isotropic group, demonstrating the rapid and sustained release behavior and longer blood circulation when combined with the results of in vivo tissue distribution studies. In summary, anisotropic nano-assemblies were found to be more promising than isotropic nano-assemblies via our in vivo and in vitro examinations.

  5. 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

  6. 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.

  7. [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.

  8. 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

  9. Contribution of Circulating Blood Cells to Survival of Mice Experiencing Endotoxemia

    DTIC Science & Technology

    1976-09-01

    challenged animals. Cortisone reduc ate damage in the liver. Cortisone apparently protects sites of endotoxin action other than blood components . Zinc, in...challenged with endotoxin through action on blood components . Furthermore, the reduction of platelets and leukocytes in 13 irradiated animals appears to...zinc, cortisone has actions on blood components and at other sites. Since cortisone protects irradiated mice from endotoxin, it is probable that it

  10. The molecular basis for the prolonged blood circulation of lipidated incretin peptides: Peptide oligomerization or binding to serum albumin?

    PubMed

    Wang, Ying; Lomakin, Aleksey; Kanai, Sonoko; Alex, Rainer; Belli, Sara; Donzelli, Massimiliano; Benedek, George B

    2016-11-10

    Hybrid incretin peptides are a new generation of drugs for the treatment of diabetes and obesity. Despite their biological potency, the effectiveness of these peptides as drugs is limited by their short circulation time in blood (typically within minutes). In this work, we show that lipid conjugated forms of a GLP-1/GIP/glucagon hybrid peptides stay in circulation for hours. We studied the oligomerization and albumin-binding of the unconjugated hybrid peptide as well as its lipidated variants. These lipidated peptides differ in the N-terminal mutation, the position of lipidation and the linkage to lipid. We found that these lipidated peptides form stable oligomers at concentrations above 1mg/mL. This concentration range is relevant to formulation and storage of the peptides. We observed no binding between the peptide oligomers and human serum albumin. However, at the expected therapeutic concentration range (~10-100ng/mL), the oligomers dissociate into monomers. The monomers of lipidated peptides bind to albumin. We have determined the dissociation constants of binding between the lipidated peptides and serum albumin. The dissociation constants of albumin-binding of our lipidated peptides are all very close and similar to that of the fatty acid binding of albumin. Our findings suggest that the monomeric lipidated peptides bind to HSA mainly by the fatty acid chain. Therefore, albumin binding is likely to be a universal mechanism of the prolonged circulating duration of lipidated pharmaceutical peptides.

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

    PubMed

    Papp, Lajos

    2008-08-03

    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.

  12. [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.

  13. Fast isolation and ex vivo culture of circulating tumor cells from the peripheral blood of lung cancer patients.

    PubMed

    Wenjun, Wu; Zhihua, Wang; Zhuo, Wang; Yuliang, Deng; Qihui, Shi

    2017-01-20

    Circulating tumor cells (CTCs) are free tumor cells shed from tumor site and enter into blood circulation. CTCs represent a reliable source of tumor cells for the molecular characteristics of the original tumor. However, the extraordinary rarity of CTCs makes the subsequent molecular and functional analysis technically challenging. Here, we describe a one-step microfludics-based immunomagnetic isolation method to isolate CTCs directly from the whole blood of lung adenocarcinoma patients. This method avoids harsh sample preparation and enrichment steps, and therefore preserves the viability (>90%) of CTCs during the in vitro isolation. The isolated CTCs are enriched in small volume (80 μL) and cultured ex vivo that leads to successful ex vivo expansion. The expanded CTCs can be frozen and thawed, which shows cell line property. Genetic sequencing on EGFR、KRAS、PIK3CA、TP53 and BRAF and metabolic assay (2-NBDG) are utilized to characterize the expanded CTCs. Our results demostrated that this method is suitable for ex vivo expansion of CTCs facilitates. The genomic, proteomic and metabolic analyses of CTCs have guiding significance in tumor precise treatment.

  14. 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.

  15. 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.

  16. 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.

  17. IL-33 promotes the migration and proliferation of circulating fibrocytes from patients with allergen-exacerbated asthma

    SciTech Connect

    Bianchetti, Lorenza; Marini, Maurizio A.; Isgro, Mirko; Bellini, Alberto; Schmidt, Matthias; Mattoli, Sabrina

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer IL-33 is considered a new therapeutic target for reducing inflammation in asthma. Black-Right-Pointing-Pointer This study shows that IL-33 is a potent chemoattractant for fibrocytes in asthma. Black-Right-Pointing-Pointer IL-33 also promotes fibrocyte proliferation without reducing collagen production. Black-Right-Pointing-Pointer The study uncovers a novel non-inflammatory, profibrotic function of IL-33. -- Abstract: The release of IL-33 increases in the bronchial mucosa of asthmatic patients in relation to disease severity and several studies have demonstrated that IL-33 may enhance airway inflammation in asthma. This study tested the hypothesis that IL-33 may also contribute to the development of irreversible structural changes in asthma by favoring the airway recruitment and profibrotic function of circulating fibrocytes during episodes of allergen-induced asthma exacerbation. The circulating fibrocytes from patients with allergen-exacerbated asthma (PwAA) showed increased expression of the specific IL-33 receptor component ST2L in comparison with the cells from non-asthmatic individuals (NAI). Recombinant IL-33 induced the migration of circulating fibrocytes from PwAA at clinically relevant concentrations and stimulated their proliferation in a concentration-dependent manner between 0.1 and 10 ng/ml, without affecting the constitutive release of type I collagen. The recombinant protein did not induce similar responses in circulating fibrocytes from NAI. This study uncovers an important mechanism through which fibrocytes may accumulate in the airways of allergic asthmatics when their disease is not adequately controlled by current treatment and provides novel information on the function of IL-33 in asthma.

  18. [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.

  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. [The effect of a dimenhydrinate combination of the cardiovascular system and cerebral blood circulation in the anaesthetized dog].

    PubMed

    Hahn, N; Felix, R; Sonnenfeld, A; Babour, A; Heidari, S

    1975-02-01

    The influence of Vertigo-Vomex (VV) and Vertigo-Vomex Retard (VVR) on the perfusion rate of the a. carotis interna and on the peripheral circulation was tested in 30 anaesthetized dogs. These drugs represent beta-dimethylamino-ethyl-benzhydrylether-1,3-dimethyl-8-chloroxanthine (dimenhydrinate, Vomex A) with the addition of pyridine-3-carbonic acid (nicotinic acid, niacin) and pyridoxine-HCl (vitamin B6) and its retard preparation. A) Angiographic researches of the brain vessels after i.v. injection of VV. B) Perfusion rate in the a. carotis int. by electromagnetic flowmeter; measurements of blood pressure, heart rate, and acid-base balance; reactions after injection of niacin, dimenhydrinate, and pyridoxine-HCl as well as after a combination of both. C) Same measurements as in B but after oral application. In one out of four cases there was a dilation of the brain vessels, in two cases there was a small one, in one case there was none. Niacin induces a short-lasting augmentation of the perfusion rate in the a. carotis int. simultaneously with rising aortic blood pressure. Dimenhydrinate with pyridoxine-HCl slightly increases the heart rate. Combined with niacin the perfusion rate shortly increases immediately after injection of niacin without any rise of blood pressure but combined with a fall in blood pH and standard bicarbonate. After oral application of VVR there was a slight but not significant augmentation of the perfusion rate in the a. carotis int. combined with rising blood pressure but with no change of the blood pH. Therefore the certain intivertigineous effect of VV and VVR cannot be explained by a rise of the perfusion rate in the inner ear or in the brain. In view of our results the central effect of dimenhydrinate combined with niacin and pyridoxine-HCl hypothetically may be improved by metabolic influences on the cells and their membranes.

  1. Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients

    PubMed Central

    Traykova, Daniela; Schneider, Beacher

    2017-01-01

    Background Recently, a complex microbiome was comprehensibly characterized in the serum and ascitic fluid of cirrhotic patients. In the current study, we investigated for the first time the induction of inflammatory pathways and Nitric Oxide, as well as the systemic hemodynamics in conjunction with the blood microbiome in a Child-Pugh class B cirrhotic cohort. Methods and Findings We used the Intestinal Infections Microbial DNA qPCR Array to screen for 53 bacterial DNA from the gut in the blood. Assays were designed using the 16S rRNA gene as a target, and PCR amplification primers (based on the Human Microbiome Project) and hydrolysis-probe detection. Eighteen systemic hemodynamic parameters were measured non-invasively by impedance cardiography using the BioZ ICG monitor. The inflammatory response was assessed by measuring blood cytokines, Nitric Oxide RNA arrays, and Nitric Oxide. In the blood of this cirrhotic cohort, we detected 19 of 53 bacterial species tested. The number of bacterial species was markedly increased in the blood of cirrhotic patients compared to control individuals (0.2+/-0.4 vs 3.1+/-2.3; 95% CI: 1.3 to 4.9; P = 0.0030). The total bacterial DNA was also increased in the blood of cirrhotic subjects compared to control subjects (0.2+/- 1.1 vs 41.8+/-132.1; 95% CI: 6.0 to 77.2; P = 0.0022). In the cirrhotic cohort, the Cardiac Output increased by 37% and the Systemic Vascular Resistance decreased by 40% (P< 0.00001 for both compared to control subjects). Systemic Vascular Resistance was inversely correlated to blood bacterial DNA quantity (- 0.621; 95% CI -0.843 to -0.218; P = 0.0060), blood bacterial species number (- 0.593; 95% CI -0.83 to -0.175; P = 0.0095; logistic regression: Chi Square = 5.8877; P = 0.0152), and serum Nitric Oxide (- 0.705; 95% CI -0.881 to -0.355; P = 0.0011). Many members of the Nitric Oxide signaling pathway gene family were increased in cirrhotic subjects. Conclusions Our study identified blood bacterial DNA in ~ 90

  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. 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

  4. Disease management to promote blood pressure control among African Americans.

    PubMed

    Brennan, Troyen; Spettell, Claire; Villagra, Victor; Ofili, Elizabeth; McMahill-Walraven, Cheryl; Lowy, Elizabeth J; Daniels, Pamela; Quarshie, Alexander; Mayberry, Robert

    2010-04-01

    African Americans have a higher prevalence of hypertension and poorer cardiovascular and renal outcomes than white Americans. The objective of this study was to determine whether a telephonic nurse disease management (DM) program designed for African Americans is more effective than a home monitoring program alone to increase blood pressure (BP) control among African Americans enrolled in a national health plan. A prospective randomized controlled study (March 2006-December 2007) was conducted, with 12 months of follow-up on each subject. A total of 5932 health plan members were randomly selected from the population of self-identified African Americans, age 23 and older, in health maintenance organization plans, with hypertension; 954 accepted, 638 completed initial assessment, and 485 completed follow-up assessment. The intervention consisted of telephonic nurse DM (intervention group) including educational materials, lifestyle and diet counseling, and home BP monitor vs. home BP monitor alone (control group). Measurements included proportion with BP < 120/80, mean systolic BP, mean diastolic BP, and frequency of BP self-monitoring. Results revealed that systolic BP was lower in the intervention group (adjusted means 123.6 vs. 126.7 mm Hg, P = 0.03); there was no difference for diastolic BP. The intervention group was 50% more likely to have BP in control (odds ratio [OR] = 1.50, 95% confidence interval [CI] 0.997-2.27, P = 0.052) and 46% more likely to monitor BP at least weekly (OR 1.46, 95% CI 1.07-2.00, P = 0.02) than the control group. A nurse DM program tailored for African Americans was effective at decreasing systolic BP and increasing the frequency of self-monitoring of BP to a greater extent than home monitoring alone. Recruitment and program completion rates could be improved for maximal impact.

  5. Prolonged blood circulation and enhanced tumor accumulation of folate-targeted dendrimer-polymer hybrid nanoparticles.

    PubMed

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

    2014-10-10

    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 50-200nm in diameter) allow for passive tumor accumulation, but hinder efficient intratumoral penetration. Conversely, smaller, actively targeted NPs (<20nm 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 (~5nm in diameter) into larger poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) NPs (~70nm). 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.

  6. The spindle pump. Development of a nonpulsatile blood pump for assisted circulation.

    PubMed

    Hager, J; Brandstaetter, F; Koller, I; Unger, F

    1989-01-01

    The spindle pump is a combined working nonpulsatile blood pump, i.e., a centrifugally propelling device. This special concept was chosen to tackle the main problems of nonpulsatile pumps, such as thromboembolic complications, sealing difficulties, and traumatic hemolysis. The first two of these problems were relatively simple to solve compared with the third problem--traumatic hemolysis. Various modifications and constructive steps of the spindle pump were necessary to keep stress on blood components within adequate limits. The actual prototype--tested in three acute experiments and eight experiments with a longer pumping duration (the longest lasting 63 hours)--is described in extenso, and its development is discussed.

  7. Mobilization of Neural Precursors in the Circulating Blood of Patients with Multiple Sclerosis

    DTIC Science & Technology

    2013-09-01

    Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002-5012. Zanotti C, Chiarini M, Serana F, Capra R...Chiarini M, Serana F, Capra R, Rottoli M, Rovaris M, Cavaletti G, Clerici R, Rezzonico M, Caimi L, Imberti L (2011) Opposite effects of interferon

  8. 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...

  9. SELEX aptamer used as a probe to detect circulating tumor cells in peripheral blood of pancreatic cancer patients.

    PubMed

    Zhang, Jinqiang; Li, Shaohua; Liu, Fang; Zhou, Lanping; Shao, Ningsheng; Zhao, Xiaohang

    2015-01-01

    Many studies have shown that the quantity and dynamics of circulating tumor cells (CTCs) in peripheral blood of patients afflicted with solid tumours have great relevance in therapeutic efficacy and prognosis. Different methods based on various strategies have been developed to isolate and identify CTCs, but their efficacy needs to be improved because of the rarity and complexity of CTCs. This study was designed to examine the possibility of using a SELEX aptamer (BC-15) as a probe to identify rare CTCs out of background nucleated cells. Aptamer BC-15 was selected from a random oligonucleotide library screened against human breast cancer tissue. Fluorescence staining showed that BC-15 had a high affinity for nuclei of human cancer cell lines of various origins as well as CTCs isolated from pancreatic cancer patients, whereas its binding capacity for non-tumor breast epithelial cells and leukocytes was almost undetectable. BC-15+/CD45- cells in cancer patient blood were also found to be cytokeratins 18-positive and aneuploid by immunofluorescence staining and fluorescent in situ hybridization, respectively. Finally, the aptamer method was compared with the well-established anti-cytokeratin method using 15 pancreatic cancer patient blood samples, and enumeration indicated no difference between these two methods. Our study establishes a novel way to identify CTCs by using a synthetic aptamer probe. This new approach is comparable with the anti-cytokeratin-based CTC identification method.

  10. 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).

  11. Correlation of Serum and Dried Blood Spot Results for Quantitation of Schistosoma Circulating Anodic Antigen: a Proof of Principle

    PubMed Central

    Downs, Jennifer A.; Corstjens, Paul L.A.M.; Mngara, Julius; Lutonja, Peter; Isingo, Raphael; Urassa, Mark; Kornelis, Dieuwke; van Dam, Govert J.

    2015-01-01

    Circulating Anodic Antigen (CAA) testing is a powerful, increasingly-used tool for diagnosis of active schistosome infection. We sought to determine the feasibility and reliability of measuring CAA in blood spots collected on Whatman 903 Protein Saver cards, which are the predominant filter papers used worldwide for dried blood spot (DBS) research and clinical care. CAA was eluted from blood spots collected from 19 individuals onto Whatman 903 cards in Mwanza, Tanzania, and the assay was optimized to achieve CAA ratios comparable to those obtained from the spots’ corresponding serum samples. The optimized assay was then used to determine the correlation of serum samples (n=16) with DBS from cards that had been stored for 8 years at ambient temperature.Using a DBS volume equivalent to approximately four times the quantity of serum, CAA testing in DBS had a sensitivity of 76% and a specificity of 79% compared to CAA testing in serum. CAA testing was reliable in samples eluted from Whatman 903 cards that had been stored for 8 years at ambient temperature. The overall kappa coefficient was 0.53 (standard error 0.17, p<0.001). We conclude that CAA can be reliably and accurately measured in DBS collected onto the filter paper that is most commonly used for clinical care and research, and that can be stored for prolonged periods of time. This finding opens new avenues for future work among more than 700 million individuals living in areas worldwide in which schistosomes are endemic. PMID:26149541

  12. 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.

  13. CIRCULATING MICROPARTICLES, BLOOD CELLS, AND ENDOTHELIUM INDUCE PROCOAGULANT ACTIVITY IN SEPSIS THROUGH PHOSPHATIDYLSERINE EXPOSURE.

    PubMed

    Zhang, Yan; Meng, Huan; Ma, Ruishuang; He, Zhangxiu; Wu, Xiaoming; Cao, Muhua; Yao, Zhipeng; Zhao, Lu; Li, Tao; Deng, Ruijuan; Dong, Zengxiang; Tian, Ye; Bi, Yayan; Kou, Junjie; Thatte, Hemant S; Zhou, Jin; Shi, Jialan

    2016-03-01

    Sepsis is invariably accompanied by altered coagulation cascade; however, the precise role of phosphatidylserine (PS) in inflammation-associated coagulopathy in sepsis has not been well elucidated. We explored the possibility of exposed PS on microparticles (MPs), blood cells, as well as on endothelium, and defined its role in procoagulant activity (PCA) in sepsis. PS-positive MPs and cells were detected by flow cytometry, while PCA was assessed with clotting time, purified coagulation complex, and fibrin formation assays. Plasma levels of PS MPs derived from platelets, leukocytes (including neutrophils, monocytes, and lymphocytes), erythrocytes, and endothelial cells were elevated by 1.49-, 1.60-, 2.93-, and 1.53-fold, respectively, in septic patients. Meanwhile, PS exposure on blood cells was markedly higher in septic patients than in controls. Additionally, we found that the endothelial cells (ECs) treated with septic serum in vitro exposed more PS than with healthy serum. Isolated MPs/blood cells from septic patients and cultured ECs treated with septic serum in vitro demonstrated significantly shortened coagulation time, greatly enhanced intrinsic/extrinsic FXa generation, and increased thrombin formation. Importantly, confocal imaging of MPs or septic serum-treated ECs identified binding sites for FVa and FXa to form prothrombinase, and further supported fibrin formation in the area where PS exposure was abundant. Pretreatment with lactadherin blocked PS on MPs/blood cells/ECs, prolonged coagulation time by at least 25%, reduced FXa/thrombin generation, and inhibited fibrin formation by approximately 85%. Our findings suggest a key role for PS exposed on MPs, blood cells, and endothelium in augmenting coagulation in sepsis. Therefore, therapies targeting PS may be of particular importance.

  14. Chemically modified, non-anticoagulant heparin derivatives are potent galectin-3 binding inhibitors and inhibit circulating galectin-3-promoted metastasis.

    PubMed

    Duckworth, Carrie A; Guimond, Scott E; Sindrewicz, Paulina; Hughes, Ashley J; French, Neil S; Lian, Lu-Yun; Yates, Edwin A; Pritchard, D Mark; Rhodes, Jonathan M; Turnbull, Jeremy E; Yu, Lu-Gang

    2015-09-15

    Concentrations of circulating galectin-3, a metastasis promoter, are greatly increased in cancer patients. Here we show that 2- or 6-de-O-sulfated, N-acetylated heparin derivatives are galectin-3 binding inhibitors. These chemically modified heparin derivatives inhibited galectin-3-ligand binding and abolished galectin-3-mediated cancer cell-endothelial adhesion and angiogenesis. Unlike standard heparin, these modified heparin derivatives and their ultra-low molecular weight sub-fractions had neither anticoagulant activity nor effects on E-, L- or P-selectin binding to their ligands nor detectable cytotoxicity. Intravenous injection of such heparin derivatives (with cancer cells pre-treated with galectin-3 followed by 3 subcutaneous injections of the derivatives) abolished the circulating galectin-3-mediated increase in lung metastasis of human melanoma and colon cancer cells in nude mice. Structural analysis using nuclear magnetic resonance and synchrotron radiation circular dichroism spectroscopies showed that the modified heparin derivatives bind to the galectin-3 carbohydrate-recognition domain. Thus, these chemically modified, non-anticoagulant, low-sulfated heparin derivatives are potent galectin-3 binding inhibitors with substantial potential as anti-metastasis/cancer drugs.

  15. Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells

    PubMed Central

    Kornek, Miroslaw; Popov, Yury; Libermann, Towia A.; Afdhal, Nezam H.; Schuppan, Detlef

    2010-01-01

    Microparticles (MP) are small cell membrane vesicles which are released from cells during apoptosis or activation. While circulating platelet MP have been studied in some detail, the existence and functional role of T cell MP remain elusive. We show that blood from patients with active hepatitis C (ALT>100 IU/ml) contains elevated numbers of T cell MP compared to patients with mild hepatitis C (ALT<40 IU/ml) and healthy controls. T cell MP fuse with cell membranes of hepatic stellate cells (HSC), the major effector cells for excess matrix deposition in liver fibrosis and cirrhosis. MP uptake is partly ICAM-1 dependent and leads to activation of NFkB and ERK1/2 and subsequent upregulation of fibrolytic genes in HSC, to downregulation of procollagen α1(I) mRNA, and blunting of profibrogenic activities of TGFβ1. Ex vivo the induced fibrolytic activity is evident in MP derived from activated CD4+ T cells, and highest with MP from activated and apoptotic CD8+ T cells. Mass spectrometry, FACS analysis and function blocking antibodies revealed CD147/Emmprin as candidate transmembrane molecule in HSC fibrolytic activation by CD8+ T cell MP. We conclude that 1) circulating T cell MP are a novel diagnostic marker for inflammatory liver diseases, and 2) in vivo induction of T cell MP may be a novel strategy to induce regression of liver fibrosis. PMID:20979056

  16. Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer.

    PubMed

    Theodoropoulos, Panayiotis A; Polioudaki, Hara; Agelaki, Sofia; Kallergi, Galatea; Saridaki, Zacharenia; Mavroudis, Dimitris; Georgoulias, Vassilis

    2010-02-01

    The CD44(+)/CD24(-/low) and ALDH1(+) cell phenotypes are associated with stemness and enhanced tumorigenic potential in breast cancer. We assessed the expression of CD44, CD24 and ALDH1 on tumor cells circulating in the peripheral blood (CTCs) of patients with metastatic breast cancer using triple-marker immunofluorescence microscopy. Among a total of 1439 CTCs identified in 20 (66.7%) out of 30 patients, 35.2% had the stem-like/tumorigenic phenotype CD44(+)/CD24(-/low), whereas 17.7% of the CTCs analyzed in seven patients, were ALDH1(high)/CD24(-/low). In conclusion, we report the existence of a subpopulation of CTCs with putative stem cell progenitor phenotypes in patients with metastatic breast cancer.

  17. Molecular Detection of Peripheral Blood Breast Cancer mRNA Transcripts as a Surrogate Biomarker for Circulating Tumor Cells

    PubMed Central

    Lasa, Adriana; Garcia, Arnal; Alonso, Carmen; Millet, Pilar; Cornet, Mónica; Cajal, Teresa Ramón y; 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. PMID:24058517

  18. Brain damage in dogs immediately following pulsatile and non-pulsatile blood flows in extracorporeal circulation

    PubMed Central

    Sanderson, J. M.; Wright, G.; Sims, F. W.

    1972-01-01

    The brains of dogs subjected to total cardiac bypass were examined for early signs of ischaemic nerve cell changes. Diffuse nerve cell changes were found immediately following two- and three-hour non-pulsatile perfusions but not following pulsatile perfusions of the same durations. The nerve cell changes found in the brains were acute cell swelling and early ischaemic cell change. Acute cell swelling was found only in the cerebellar Purkinje cells. Ischaemic cell change was found in several regions of the brain but the cerebral cortex and cerebellar Purkinje cells were most frequently affected. Diffuse nerve cell changes are attributed to non-pulsatile blood flow but some complicating factors are recognized. Focal lesions found in three brains may have been due to embolism by blood cell aggregates and/or gas microbubbles. Images PMID:5039442

  19. [Detection of fetal nucleated red blood cells in the maternal circulation by Kleihauer test].

    PubMed

    Liu, Wei-Yu; Jin, Chun-Lian; Liu, Li-Ying; Lin, Chang-Kun; Wang, Yan; Sun, Kai-Lai

    2007-03-01

    Maternal blood was obtained from 18 pregnant women at 7 to 25 weeks of gestation. After Percoll discontinuous density gradient centifugation, the fetal nucleated red blood cells (NRBCs) were stained with Kleihauer test. Positive fetal cells appeared with an intense red cytoplasmic staining while maternal cells with adult haemoglobin were colourless. Individual positive NRBC was collected by micromanipulator and whole genome amplification was then performed to determine sex and STR status. This allowed the simultaneous verification of the fetal origin of NRBC and prenatal diagnosis of genetic diseases. The non-invasive prenatal genetic diagnosis of 9 fetuses at high risk of Duchenne muscular dystrophy (DMD) was completed successfully. The Kleihauer test is a rapid, simple and direct chemical staining method to select fetal cells and can be applied in prenatal diagnosis.

  20. 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.

  1. 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.

  2. [The action of emoxipin, lithium oxybutyrate and pikamilon on the blood circulation of the ischemic brain].

    PubMed

    Pogorelyĭ, V E; Gaevyĭ, M D

    1999-01-01

    Acute experiments were conducted on rats under nembutal anesthesia to compare the efficacy of emoxipin with that of lithium oxybutyrate and picamilon in the postischemic period after preventive and therapeutic injections in various doses. Emoxipin proved to be most effective in prevention of postischemic non-restoration of the flow of blood in the brain and in preservation of the autoregulation responses of the cerebral vessels. The possible mechanisms of the effect of the drug are discussed.

  3. 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

  4. Feasibility of a miniature centrifugal rotary blood pump for low-flow circulation in children and infants.

    PubMed

    Takatani, Setsuo; Hoshi, Hideo; Tajima, Kennichi; Ohuchi, Katsuhiro; Nakamura, Makoto; Asama, Junichio; Shimshi, Tadahiko; Yoshikawa, Masaharu

    2005-01-01

    In this study, a seal-less, tiny centrifugal rotary blood pump was designed for low-flow circulatory support in children and infants. The design was targeted to yield a compact and priming volume of 5 ml with a flow rate of 0.5-4 l/min against a head pressure of 40-100 mm Hg. To meet the design requirements, the first prototype had an impeller diameter of 30 mm with six straight vanes. The impeller was supported with a needle-type hydrodynamic bearing and was driven with a six-pole radial magnetic driver. The external pump dimensions included a pump head height of 20 mm, diameter of 49 mm, and priming volume of 5 ml. The weight was 150 g, including the motor driver. In the mock circulatory loop, using fresh porcine blood, the pump yielded a flow of 0.5-4.0 l/min against a head pressure of 40-100 mm Hg at a rotational speed of 1800-4000 rpm using 1/4" inflow and outflow conduits. The maximum flow and head pressure of 5.25 l/min and 244 mm Hg, respectively, were obtained at a rotational speed of 4400 rpm. The maximum electrical-to-hydraulic efficiency occurred at a flow rate of 1.5-3.5 l/min and at a rotational speed of 2000-4400 rpm. The normalized index of hemolysis, which was evaluated using fresh porcine blood, was 0.0076 g/100 l with the impeller in the down-mode and a bearing clearance of 0.1 mm. Further refinement in the bearing and magnetic coupler are required to improve the hemolytic performance of the pump. The durability of the needle-type hydrodynamic bearing and antithrombotic performance of the pump will be performed before clinical applications. The tiny centrifugal blood pump meets the flow requirements necessary to support the circulation of pediatric patients.

  5. 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

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

    2011-10-01

    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 (Indocyanine Green [ICG], Methylene Blue [MB], and Trypan Blue [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 Crystal Violet and Brilliant Green 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, and 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.

  6. Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis.

    PubMed

    Zhu, Jing-Cheng; Si, Meng-Ya; Li, Ya-Zhen; Chen, Huan-Zhu; Fan, Zhi-Cheng; Xie, Qing-Dong; Jiao, Xiao-Yang

    2016-03-21

    The aim of this study was to evaluate the clinical significance of circulating tight junction (TJ) proteins as biomarkers reflecting of leukaemia central nervous system (CNS) metastasis. TJs [claudin5 (CLDN5), occludin (OCLN) and ZO-1] concentrations were measured in serum and cerebrospinal fluid (CSF) samples obtained from 45 leukaemia patients. Serum ZO-1 was significantly higher (p < 0.05), but CSF ZO-1 levels were not significantly higher in the CNS leukaemia (CNSL) compared to the non-CNSL. The CNSL patients also had a lower CLDN5/ZO1 ratio in both serum and CSF than in non-CNSL patients (p < 0.05). The TJ index was negatively associated with WBCCSF , ALBCSF and BBB values in leukaemia patients. Among all of the parameters studied, CLDN5CSF had the highest specificity in discriminating between CNSL and non-CNSL patients. Therefore, analysing serum and CSF levels of CLDN5, OCLN and the CLDN5/ZO1 ratio is valuable in evaluating the potential of leukaemia CNS metastasis. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Detection and preliminary evaluation of circulating tumor cells in the peripheral blood of patients with eight types of cancer using a telomerase-specific adenovirus.

    PubMed

    Yabusaki, Mina; Sato, Jun; Kohyama, Atsushi; Kojima, Takashi; Nobuoka, Daisuke; Yoshikawa, Toshiaki; Sawada, Yu; Murakami, Katsuhiro; Gohda, Keigo; Okegawa, Takatsugu; Nakamura, Masaru; Takamatsu, Kiyoshi; Ito, Masaaki; Kaneko, Kazuhiro; Nakatsura, Tetsuya

    2014-11-01

    We developed a detection method for circulating tumor cells (CTCs) using the telomerase-specific adenovirus OBP-401. This recombinant virus has a telomerase promoter at the 5'-end of the viral genome and GFP at the 3'-end. To date, CTC enumeration using OBP-401 has shown prognostic impact for gastric and small cell lung cancer patients. In the present study, peripheral blood samples from patients with eight types of cancer, including some cancers previously untested with OBP-401 (i.e., esophagus, pancreas, and prostate cancers) were subjected to this method in order to evaluate its versatility. It was recently discovered that some white blood cells (WBCs) false-positively react with OBP-401. Although anti-CD45 antibodies can absorb these adverse cells from peripheral blood, the simplicity of the OBP-401 method would be diminished by the introduction of antibody treatment. Therefore, we evaluated another approach to minimize the false positivity of WBCs. Seven anti-CD antibodies were employed to stain the species of WBCs that false-positively reacted with OBP-401. We revealed that the false-positively reacted WBCs were monocytes in the peripheral blood of both healthy subjects and cancer patients. Based on a size distribution analysis of the GFP-positive monocytes, the size criterion for CTCs using OBP-401 was defined to be a cellular diameter>8.4 µm. In total, 43% of 86 cancer patients examined in the present study were CTC-positive using this definition. CTCs were enumerated from peripheral blood samples collected from patients with each of the eight types of cancer; the detectability of CTCs for esophagus, pancreas and prostate cancers by the OBP-401 method was confirmed for the first time in the present study. However, no clear correlation between CTC positivity and the clinical characteristics of patients with any type of cancer was observed because of the small number of patients with each type of cancer. An additional clinical study will be conducted to

  8. Blood circulating tumor DNA for non-invasive genotyping of colon cancer patients.

    PubMed

    Siravegna, Giulia; Bardelli, Alberto

    2016-03-01

    Most solid tumors, including colorectal cancers, shed cell-free DNA (ctDNA) in the blood. ctDNA can be analyzed to generate molecular profiles which capture the heterogeneity of the disease more comprehensively then tumor tissue biopsies. This approach commonly called 'liquid biopsy' can be applied to monitor response to therapy, to assess minimal residual disease and to uncover the emergence of drug resistance. This review will discuss current and future developments of ctDNA analysis in the clinical management of colorectal cancer patients.

  9. [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.

  10. Encapsulation of FITC to monitor extracellular pH: a step towards the development of red blood cells as circulating blood analyte biosensors.

    PubMed

    Ritter, Sarah C; Milanick, Mark A; Meissner, Kenith E

    2011-07-01

    A need exists for a long-term, minimally-invasive system to monitor blood analytes. For certain analytes, such as glucose in the case of diabetics, a continuous system would help reduce complications. Current methods suffer significant drawbacks, such as low patient compliance for the finger stick test or short lifetime (i.e., 3-7 days) and required calibrations for continuous glucose monitors. Red blood cells (RBCs) are potential biocompatible carriers of sensing assays for long-term monitoring. We demonstrate that RBCs can be loaded with an analyte-sensitive fluorescent dye. In the current study, FITC, a pH-sensitive fluorescent dye, is encapsulated within resealed red cell ghosts. Intracellular FITC reports on extracellular pH: fluorescence intensity increases as extracellular pH increases because the RBC rapidly equilibrates to the pH of the external environment through the chloride-bicarbonate exchanger. The resealed ghost sensors exhibit an excellent ability to reversibly track pH over the physiological pH range with a resolution down to 0.014 pH unit. Dye loading efficiency varies from 30% to 80%. Although complete loading is ideal, it is not necessary, as the fluorescence signal is an integration of all resealed ghosts within the excitation volume. The resealed ghosts could serve as a long-term (>1 to 2 months), continuous, circulating biosensor for the management of diseases, such as diabetes.

  11. 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.

  12. [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.

  13. A STUDY OF THE CIRCULATION, BLOOD PRESSURE, AND RESPIRATION OF SHARKS.

    PubMed

    Lyon, E P

    1926-01-04

    The average branchial blood pressure in sand sharks was 32 mm. of mercury. The highest recorded in a resting animal was 43 mm. The average dorsal or systemic pressure was 23.3 mm.; highest 30 mm. The ratio of branchial to systemic pressure is about 3 to 2. The pressure in both systems keeps up well under trauma; but under experimental conditions, with or without manipulation of viscera, slowly falls after several hours. It rises with muscular effort, and a long rise usually follows stoppage of struggling. It rises when sodium carbonate is injected. The adrenalin curve resembles that in a mammal. Spontaneous rises and falls not attributable to the heart occur. Light in some animals increases blood pressure. It is suspected that these fishes have a vasomotor apparatus. The heart rate except after trauma is practically always the same as the respiration rate, and there is some reason for believing that the heart rate is determined by the respiration rate. When not in step with respiration, the heart is slower and often in a simple ratio with respiration. The heart is inhibited by all sorts of stimuli applied practically anywhere (except to the liver?). This effect is abolished by atropin. Respiration is faster in small animals and averages 24 per minute. Respiration slowly decreases in strength with little change in rate. Usually respiration ceases long before the heart stops.

  14. 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.

  15. 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.

  16. 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

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

    PubMed

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

    2016-04-07

    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.

  18. KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control

    PubMed Central

    Le Calvez-Kelm, Florence; Foll, Matthieu; Wozniak, Magdalena B.; Delhomme, Tiffany M.; Durand, Geoffroy; Chopard, Priscilia; Pertesi, Maroulio; Fabianova, Eleonora; Adamcakova, Zora; Holcatova, Ivana; Foretova, Lenka; Janout, Vladimir; Vallee, Maxime P.; Rinaldi, Sabina; Brennan, Paul; McKay, James D.; Byrnes, Graham B.; Scelo, Ghislaine

    2016-01-01

    The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series. PMID:27705932

  19. 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.

  20. 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.

  1. Correlation between circulating biomarkers of oxidative stress of maternal and umbilical cord blood at birth.

    PubMed

    Argüelles, Sandro; Machado, Maria José; Ayala, Antonio; Machado, Alberto; Hervías, Blas

    2006-06-01

    The objective of the work was to study the relationship between the oxidative state of the mother and the newborn at the moment of birth. We measured oxidative stress markers (carbonyl groups, lipid peroxides and total antioxidant capacity (TAC)) and found a good correlation between the oxidative state of the normal mother and the neonate, since a high mother oxidative stress corresponds to an even higher oxidative stress of the newborn in umbilical cord blood. We also found that smoking mothers and their newborns had a higher concentration of the carbonyl group, lipid peroxides and less TAC. Newborns from these mothers weighed significantly less than others at birth. These data suggest a need for interest in monitoring the oxidative state of mothers during the pregnancy period, especially taking into account that the oxidative level could be involved in later risks of metabolic diseases for both mother and newborn.

  2. 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

  3. High concentration of branched-chain amino acids promotes oxidative stress, inflammation and migration of human peripheral blood mononuclear cells via mTORC1 activation.

    PubMed

    Zhenyukh, Olha; Civantos, Esther; Ruiz-Ortega, Marta; Sánchez, Maria Soledad; Vázquez, Clotilde; Peiró, Concepción; Egido, Jesús; Mas, Sebastián

    2017-03-01

    Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. In cultured PBMCs, 10mmol/L BCAA increased the production of reactive oxygen species (ROS) via both NADPH oxidase and the mitochondria, and activated Akt-mTOR signalling. By using several inhibitors and activators of these molecular pathways we have described that mTOR activation by BCAA is linked to ROS production and mitochondrial dysfunction. BCAA stimulated the activation of the redox-sensitive transcription factor NF-κB, which resulted in the release of pro-inflammatory molecules, such as interleukin-6, tumor necrosis factor-α, intracellular adhesion molecule-1 or CD40L, and the migration of PBMCs. In conclusion, elevated BCAA blood levels can promote the activation of circulating PBMCs, by a mechanism that involving ROS production and NF-κB pathway activation. These data suggest that high concentrations of BCAA could exert deleterious effects on circulating blood cells and therefore contribute to the pro-inflammatory and oxidative status observed in several pathophysiological conditions.

  4. Increased blood-circulating interferon-γ, interleukin-17, and osteopontin levels in bovine paratuberculosis.

    PubMed

    Dudemaine, P L; Fecteau, G; Lessard, M; Labrecque, O; Roy, J P; Bissonnette, N

    2014-01-01

    Paratuberculosis-infected cattle initially develop an effective cell-mediated immune response that declines as the disease progresses. Blood is one of best sources for characterizing the inflammatory status of infected cows and for studying mediators related to chronic diseases. The aim of this study was to evaluate the cow-level association between blood cytokine concentration, the influence of serum on immune cell proliferation, and dairy cows naturally infected with Mycobacterium avium ssp. paratuberculosis (MAP). Positive animals (n=41) from 19 herds were selected on the basis of 2 positive fecal culture results and divided into 2 groups: single-positive, or serum ELISA-negative cows (n=32), and double-positive, or cows that gave positive results for both mycobacterial culture and serum ELISA (n=9). Negative animals (n=39) were selected from paratuberculosis-negative herds in which at least 80% of the animals had been diagnosed as negative by fecal culture and ELISA and that did not produce positive results during the 2-yr study. Analysis of plasma levels of the cytokines IL-4, IL-10, IL-17, IFN-γ, and osteopontin was performed, revealing distinct patterns. The ELISA-positive cows with MAP shedding had similar plasma concentrations of IL-4 and IL-10 but elevated levels of IFN-γ, IL-17, and osteopontin, which is indicative of inflammatory disease in these subclinical positive cows. In vitro MAP infection of bovine macrophages showed increased gene expression of tumor necrosis factor-α, IL-1β, IL-6, IL-23, and transforming growth factor-β as early as 6h postinfection for all of the cytokines involved in the establishment of a T-helper type-17 immune response. To determine the systemic influence of serum on immune cell functions, lymphoproliferation assays were also performed in presence of JD serum. The serum from shedding cows showed 15% less proliferation. These results indicate that infected cows have a lower systemic capacity to maintain a protective

  5. 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

  6. 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

  7. The spatial arrangement of the human large intestinal wall blood circulation.

    PubMed

    Kachlik, David; Baca, Vaclav; Stingl, Josef

    2010-03-01

    The aim of the study was to describe and depict the spatial arrangement of the colon microcirculatory bed as a whole. Various parts of the large intestine and terminal ileum were harvested from either cadaver or section material or gained peroperatively. Samples were then injected with India ink or methylmetacrylate Mercox resin for microdissection and corrosion casting for scanning electron microscopy. The results showed that extramural vasa recta ramified to form the subserous plexus, some of them passing underneath the colon taeniae. Branches of both short and long vasa recta merged in the colon wall, pierced the muscular layer and spread out as the submucous plexus, which extended throughout the whole intestine without any interruption. The muscular layer received blood via both the centrifugal branches of the submucous plexus and the minor branches sent off by the subserous plexus. The mucosa was supplied by the mucous plexus, which sent capillaries into the walls of intestinal glands. The hexagonal arrangement of the intestinal glands reflected their vascular bed. All three presumptive critical points are only gross anatomical points of no physiological relevance in healthy individuals. Neither microscopic weak points nor regional differences were proven within the wall of the whole large intestine. The corrosion casts showed a huge density of capillaries under the mucosa of the large intestine. A regular hexagonal pattern of the vascular bed on the inner surface was revealed. No microvascular critical point proofs were confirmed and a correlation model to various pathological states was created.

  8. The spatial arrangement of the human large intestinal wall blood circulation

    PubMed Central

    Kachlik, David; Baca, Vaclav; Stingl, Josef

    2010-01-01

    The aim of the study was to describe and depict the spatial arrangement of the colon microcirculatory bed as a whole. Various parts of the large intestine and terminal ileum were harvested from either cadaver or section material or gained peroperatively. Samples were then injected with India ink or methylmetacrylate Mercox resin for microdissection and corrosion casting for scanning electron microscopy. The results showed that extramural vasa recta ramified to form the subserous plexus, some of them passing underneath the colon taeniae. Branches of both short and long vasa recta merged in the colon wall, pierced the muscular layer and spread out as the submucous plexus, which extended throughout the whole intestine without any interruption. The muscular layer received blood via both the centrifugal branches of the submucous plexus and the minor branches sent off by the subserous plexus. The mucosa was supplied by the mucous plexus, which sent capillaries into the walls of intestinal glands. The hexagonal arrangement of the intestinal glands reflected their vascular bed. All three presumptive critical points are only gross anatomical points of no physiological relevance in healthy individuals. Neither microscopic weak points nor regional differences were proven within the wall of the whole large intestine. The corrosion casts showed a huge density of capillaries under the mucosa of the large intestine. A regular hexagonal pattern of the vascular bed on the inner surface was revealed. No microvascular critical point proofs were confirmed and a correlation model to various pathological states was created. PMID:20447248

  9. [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.

  10. Methylation status of the APC and RASSF1A promoter in cell-free circulating DNA and its prognostic role in patients with colorectal cancer.

    PubMed

    Matthaios, Dimitrios; Balgkouranidou, Ioanna; Karayiannakis, Anastasios; Bolanaki, Helen; Xenidis, Nikolaos; Amarantidis, Kyriakos; Chelis, Leonidas; Romanidis, Konstantinos; Chatzaki, Aikaterini; Lianidou, Evi; Trypsianis, Grigorios; Kakolyris, Stylianos

    2016-07-01

    DNA methylation is the most frequent epigenetic alteration. Using methylation-specific polymerase chain reaction (MSP), the methylation status of the adenomatous polyposis coli (APC) and Ras association domain family 1 isoform A (RASSF1A) genes was examined in cell-free circulating DNA from 155 plasma samples obtained from patients with early and advanced colorectal cancer (CRC). APC and RASSF1A hypermethylation was frequently observed in both early and advanced disease, and was significantly associated with a poorer disease outcome. The methylation status of the APC and RASSF1A promoters was investigated in cell-free DNA of patients with CRC. Using MSP, the promoter methylation status of APC and RASSF1A was examined in 155 blood samples obtained from patients with CRC, 88 of whom had operable CRC (oCRC) and 67 had metastatic CRC (mCRC). The frequency of APC methylation in patients with oCRC was 33%. Methylated APC promoter was significantly associated with older age (P=0.012), higher stage (P=0.014) and methylated RASSF1A status (P=0.050). The frequency of APC methylation in patients with mCRC was 53.7%. In these patients, APC methylation was significantly associated with methylated RASSF1A status (P=0.016). The frequency of RASSF1A methylation in patients with oCRC was 25%. Methylated RASSF1A in oCRC was significantly associated with higher stage (P=0.021). The frequency of RASSF1A methylation in mCRC was 44.8%. Methylated RASSF1A in mCRC was associated with moderate differentiation (P=0.012), high levels of carcinoembryonic antigen (P=0.023) and methylated APC status (P=0.016). Patients with an unmethylated APC gene had better survival in both early (81±5 vs. 27±4 months, P<0.001) and advanced disease (37±7 vs. 15±3 months, P<0.001), compared with patients with methylated APC. Patients with an unmethylated RASSF1A gene had better survival in both early (71±6 vs. 46±8 months, P<0.001) and advanced disease (28±4 vs. 16±3 months, P<0.001) than patients with

  11. [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.

  12. Increases in circulating megakaryocyte growth-promoting activity in the plasma of rats following whole body irradiation

    SciTech Connect

    Miura, M.; Jackson, C.W.; Lyles, S.A.

    1984-05-01

    To gain insight into the regulation of megakaryocyte precursors in vivo, we assayed (in vitro) megakaryocyte growth-promoting activity (Meg-GPA) in plasma of rats in which both marrow hypoplasia and thrombocytopenia had been induced by irradiation. Rats received whole body irradiation of 834 rad from a /sup 137/Cs source. Plasma was collected at intervals of hours to days, up through day 21 postirradiation, and was tested, at a concentration of 30%, for Meg-GPA on bone marrow cells cultured in 1.1% methylcellulose with 5 X 10(-5) M 2-mercaptoethanol. With normal rat plasma, no megakaryocyte colonies (defined as greater than or equal to 4 megakaryocytes) were seen and only a few single megakaryocytes and clusters (defined as 2 or 3 megakaryocytes) were formed. Two peaks of plasma Meg-GPA were observed after irradiation. The first appeared at 12 hr, before any decrease in marrow megakaryocyte concentration or platelet count. The second occurred on days 10-14 after irradiation, after the nadir in megakaryocyte concentration and while platelet counts were at their lowest levels. A dose-response study of plasma concentration and megakaryocyte growth, using plasma collected 11 days postirradiation, demonstrated that patterns of megakaryocyte growth were related to plasma concentration; formation of single megakaryocytes was optimal over a range of 20%-30% plasma concentration, while cluster and colony formation were optimal at a plasma concentration of 30%. All forms of megakaryocyte growth were decreased with 40% plasma. There was a linear relationship between the number of bone marrow cells plated and growth of single cells, clusters, and colonies using a concentration of 30% plasma collected 11 days after irradiation. We conclude that irradiation causes time-related increases in circulating megakaryocyte growth-promoting activity.

  13. 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.

  14. An elevated level of circulating galanin promotes developmental expression of myelin basic protein in the mouse brain.

    PubMed

    Lyubetska, H; Zhang, L; Kong, J; Vrontakis, M

    2015-01-22

    Myelinogenesis is a scheduled process that is regulated by the intrinsic properties of the cell and extracellular signals. Galanin (GAL) is a bioactive neuropeptide that is widely distributed throughout the nervous system. Chronic increase in circulating GAL levels protects the demyelination processes. Furthermore, GAL is synthesized in myelin-producing glial cells, such as oligodendrocytes and its expression level is at its highest between postnatal days 10 and 40. In the present study, we use our GAL transgenic mouse model to examine the effects of GAL on postnatal myelinogenesis in the CNS. Although we observed no difference in the proliferation of oligodendrocyte precursor cells, we found that GAL has a strong pro-myelinating effect. The transgenic mice at postnatal day 10 appeared to undergo myelinogenesis at an accelerated rate, as demonstrated by the increase in myelin basic protein (MBP) synthesis. The immunohistochemical results are consistent with our preliminary findings that suggest that GAL is a regulator of myelination and may be one of the myelination promoters. This finding is especially important for studies focusing on endogenous molecules for treating myelin-related diseases, such as multiple sclerosis and other leukodystrophies.

  15. Fetal Circulation

    MedlinePlus

    ... Echocardiography/Your Unborn Baby's Heart - Fetal Echocardiogram Test - Detection of a Heart Defect - Fetal Circulation • Care & Treatment • Tools & Resources Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Target Heart Rates 4 Heart Attack Symptoms in Women ...

  16. Restoring the youth of aged red blood cells and extending their lifespan in circulation by remodelling membrane sialic acid.

    PubMed

    Huang, Yao-Xiong; Tuo, Wei-Wei; Wang, Di; Kang, Li-Li; Chen, Xing-Yao; Luo, Man

    2016-02-01

    Membrane sialic acid (SA) plays an important role in the survival of red blood cells (RBCs), the age-related reduction in SA content negatively impacts both the structure and function of these cells. We have therefore suggested that remodelling the SA in the membrane of aged cells would help recover cellular functions characteristic of young RBCs. We developed an effective method for the re-sialylation of aged RBCs by which the cells were incubated with SA in the presence of cytidine triphosphate (CTP) and α-2,3-sialytransferase. We found that RBCs could be re-sialylated if they had available SA-binding groups and after the re-sialylation, aged RBCs could restore their membrane SA to the level in young RBCs. Once the membrane SA was restored, the aged RBCs showed recovery of their biophysical and biochemical properties to similar levels as in young RBCs. Their life span in circulation was also extended to twofold. Our findings indicate that remodelling membrane SA not only helps restore the youth of aged RBCs, but also helps recover injured RBCs.

  17. 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.

  18. A functional requirement for astroglia in promoting blood vessel development in the early postnatal brain.

    PubMed

    Ma, Shang; Kwon, Hyo Jun; Huang, Zhen

    2012-01-01

    Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net decreases in vessel density between different stages after normalizing for cortical expansion nor obvious apoptosis of endothelial cells in these mutants. Furthermore, concomitant with loss of astroglial interactions, we find increased endothelial cell proliferation, enlarged vessel luminal size as well as enhanced cytoskeletal gene expression in pericytes, which suggests compensatory changes in vascular cells. Lastly, we find that blood vessel morphology in mutant cortices recovers substantially at later stages, following astrogliosis. These results thus implicate a functional requirement for astroglia in promoting blood vessel growth during brain development.

  19. 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.

  20. 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.

  1. A Single Session of Neuromuscular Electrical Stimulation Enhances Vascular Endothelial Function and Peripheral Blood Circulation in Patients With Acute Myocardial Infarction.

    PubMed

    Tanaka, Shinya; Masuda, Takashi; Kamiya, Kentaro; Hamazaki, Nobuaki; Akiyama, Ayako; Kamada, Yumi; Maekawa, Emi; Noda, Chiharu; Yamaoka-Tojo, Minako; Ako, Junya

    2016-12-02

    This study aimed to investigate whether a single session of neuromuscular electrical stimulation (NMES) can enhance vascular endothelial function and peripheral blood circulation in patients with acute myocardial infarction (AMI). Thirty-four male patients with AMI were alternately assigned to 2 groups, and received NMES with muscle contraction (NMES group, n = 17) or without muscle contraction (control group, n = 17) after admission. NMES was performed for quadriceps and gastrocnemius muscles of both legs for 30 minutes. We measured systolic blood pressure as a parameter of cardiovascular responses and the low-frequency component of blood pressure variability as an index of sympathetic activity. Reactive hyperemia peripheral arterial tonometry (RH-PAT) index and transcutaneous oxygen pressure in foot (Foot-tcPO2) were also measured as parameters of vascular endothelial function and peripheral blood circulation, respectively. All patients completed the study without severe adverse events. Systolic blood pressure and the low-frequency component increased significantly during the NMES session in both groups (P < 0.01 and P < 0.05, respectively). However, elevation from systolic blood pressure at rest was < 10 mmHg in both groups. In the NMES group, the RH-PAT index and Foot-tcPO2 increased significantly after NMES (P < 0.05 and P < 0.001, respectively). No significant changes were observed in these parameters throughout the session in the control group. In conclusion, a single session of NMES with muscle contraction enhanced vascular endothelial function, leading to improvement in peripheral blood circulation without inducing excessive cardiovascular and autonomic responses in patients with AMI (UMIN000014196).

  2. Is there a "magic" hemoglobin number? Clinical decision support promoting restrictive blood transfusion practices.

    PubMed

    Goodnough, Lawrence Tim; Shah, Neil

    2015-10-01

    Blood transfusion has been identified as one of the most frequently performed therapeutic procedures, with a significant percentage of transfusions identified to be inappropriate. Recent key clinical trials in adults have provided Level 1 evidence to support restrictive red blood cell (RBC) transfusion practices. However, some advocates have attempted to identify a "correct" Hb threshold for RBC transfusion; whereas others assert that management of anemia, including transfusion decisions, must take into account clinical patient variables, rather than simply one diagnostic laboratory test. The heterogeneity of guidelines for blood transfusion by a number of medical societies reflects this controversy. Clinical decision support (CDS) uses a Hb threshold number in a smart Best Practices Alert (BPA) upon physician order, to trigger a concurrent utilization self-review for whether blood transfusion therapy is appropriate. This review summarizes Level 1 evidence in seven key clinical trials in adults that support restrictive transfusion practices, along strategies made possible by CDS that have demonstrated value in improving blood utilization by promoting restrictive transfusion practices.

  3. 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.

  4. Highly efficient assay of circulating tumor cells by selective sedimentation with a density gradient medium and microfiltration from whole blood.

    PubMed

    Park, Jong-Myeon; Lee, June-Young; Lee, Jeong-Gun; Jeong, Hyoyoung; Oh, Jin-Mi; Kim, Yeon Jeong; Park, Donghyun; Kim, Minseok S; Lee, Hun Joo; Oh, Jin Ho; Lee, Soo Suk; Lee, Won-Yong; Huh, Nam

    2012-09-04

    Isolation of circulating tumor cells (CTCs) by size exclusion can yield poor purity and low recovery rates, due to large variations in size of CTCs, which may overlap with leukocytes and render size-based filtration methods unreliable. This report presents a very sensitive, selective, fast, and novel method for isolation and detection of CTCs. Our assay platform consists of three steps: (i) capturing CTCs with anti-EpCAM conjugated microbeads, (ii) removal of unwanted hematologic cells (e.g., leukocytes, erythrocytes, etc.) by selective sedimentation of CTCs within a density gradient medium, and (iii) simple microfiltration to collect these cells. To demonstrate the efficacy of this assay, MCF-7 breast cancer cells (average diameter, 24 μm) and DMS-79 small cell lung cancer cells (average diameter, 10 μm) were used to model CTCs. We investigated the relative sedimentation rates for various cells and/or particles, such as CTCs conjugated with different types of microbeads, leukocytes, and erythrocytes, in order to maximize differences in the physical properties. We observed that greater than 99% of leukocytes in whole blood were effectively removed at an optimal centrifugal force, due to differences in their sedimentation rates, yielding a much purer sample compared to other filter-based methods. We also investigated not only the effect of filtration conditions on recovery rates and sample purity but also the sensitivity of our assay platform. Our results showed a near perfect recovery rate (~99%) for MCF-7 cells and very high recovery rate (~89%) for DMS-79 cells, with minimal amounts of leukocytes present.

  5. Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in Treatment of Severe Pulmonary Aspergillosis in Leukopenic Rats

    PubMed Central

    Van Etten, Els W. M.; Stearne-Cullen, Lorna E. T.; Ten Kate, Marian T.; Bakker-Woudenberg, Irma A. J. M.

    2000-01-01

    The therapeutic efficacy of long-circulating polyethylene glycol-coated liposomal amphotericin B (AMB) (PEG-AMB-LIP) was compared with that of AMB desoxycholate (Fungizone) in a model of severe invasive pulmonary aspergillosis in persistently leukopenic rats as well as in temporarily leukopenic rats. PEG-AMB-LIP treatment (intravenous administration) consisted of a single, or double (every 72 h), or triple (every 72 h) dose of 10 mg of AMB/kg of body weight, a double dose (every 72 h) of 14 mg of AMB/kg, or a 5-day treatment (every 24 h) with 6 mg/kg/dose. AMB desoxycholate was administered for 10 consecutive days at 1 mg of AMB/kg/dose. Treatment was started 30 h after fungal inoculation, at which time mycelial growth was firmly established. Both persistently and temporarily leukopenic rats died between 4 and 9 days after Aspergillus fumigatus inoculation when they were left untreated or after treatment with a placebo. In persistently leukopenic rats, a single dose of PEG-AMB-LIP (10 mg/kg) was as effective as the 10-day treatment with AMB desoxycholate (at 1 mg/kg/dose) in significantly prolonging the survival of rats infected with A. fumigatus and in reducing the dissemination of A. fumigatus to the liver. Prolongation of PEG-AMB-LIP treatment (double or triple dose or 5-day treatment) did not further improve efficacy. For temporarily leukopenic rats no major advances in efficacy were achieved compared to those for persistently leukopenic rats, probably because the leukocyte numbers in blood were restored too late in the course of infection. PMID:10681315

  6. 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

  7. Temporal profiles of blood pressure, circulating nitric oxide, and adrenomedullin as predictors of clinical outcome in acute ischemic stroke patients

    PubMed Central

    SERRANO-PONZ, MARTA; RODRIGO-GASQUÉ, CARMEN; SILES, EVA; MARTÍNEZ-LARA, ESTHER; OCHOA-CALLEJERO, LAURA; MARTÍNEZ, ALFREDO

    2016-01-01

    Stroke remains an important health and social challenge. The present study investigated whether blood pressure (BP) parameters and circulating levels of nitric oxide metabolites (NOx) and adrenomedullin (AM) may predict clinical outcomes of stroke. Patients (n=76) diagnosed with acute ischemic stroke were admitted to the stroke unit and clinical history data and monitored parameters were recorded. Blood plasma was collected at days 1, 2, and 7 to measure NOx and AM levels. Infarct volume, neurological severity [on the National Institutes of Health Stroke Scale (NIHSS)], and functional prognosis (on the Rankin scale) were measured as clinical outcomes. Patients with higher BP had more severe symptoms (NIHSS >3; P<0.01) and BP variability predicted neurological severity and growth of infarct volume. NOx values were significantly lower in stroke patients than in healthy controls (P<0.01). An increase in NOx levels from day 1 to day 2 was beneficial for the patients as measured by NIHSS at 7 days and 3 months, and by Rankin at 3 months [odds ratio (OR), 0.91] whereas a steep increase from day 2 to day 7 was detrimental and associated with an increase in infarct volume (OR, 35.3). AM levels were significantly higher in patients at day 1 and 2 than in healthy individuals (P<0.01) and these levels returned to normal at day 7. Patients with high AM levels at day 2 had significantly higher NIHSS scores measured at day 1 (P<0.05) and 7 (P<0.01). A receiving operating characteristic curve analysis identified that AM levels at day 2 of >522.13 pg/ml predicted increased neurological severity at day 7 (area under the curve=0.721). Multivariate logistic regression indicated that AM levels at day 2 predicted increased neurological severity at 7 days and at 3 months. BP parameters and changing levels for NOx and AM predicted long-term clinical outcomes as measured by infarct volume, neurological severity scale, and functional prognosis. PMID:27035412

  8. Homocysteine and its thiolactone may promote apoptotic events in blood platelets in vitro.

    PubMed

    Olas, Beata; Malinowska, Joanna; Rywaniak, Joanna

    2010-01-01

    The actions of homocysteine and its major metabolite, cyclic thioester, homocysteine thiolactone on endothelial cells, blood platelets, plasmatic fibrinogen and plasminogen--the important major components of haemostasis, regulating the flowing properties of blood--are complex and sometimes controversial. Homocysteine (Hcys) can promote apoptosis in endothelial cells, but the role of Hcys and its thiolactone in the apoptotic process in blood platelets is unknown. In order to study the appearance of apoptosis in platelets after treatment with the reduced form of Hcys or its thiolactone different markers were chosen: annexin V binding (phosphatidylserine exposure), platelet microparticle formation, mitochondrial membrane depolarization and αIIbβ3 expression in vitro. Apoptotic events and platelet activation were measured by a flow cytometer. In gel-filtered platelets treated with different concentrations of the reduced form of Hcys (25, 50 and 100 µM, 10 min) a significant increase of phosphatidylserine exposure (about 37% at the highest concentration, p < 0.001) and platelet microparticle formation were observed. Homocysteine caused also a dose-dependent depolarization of mitochondrial potential. The same apoptotic markers appeared in HTL-treated platelets (0.2 and 1 µM). Moreover, resveratrol (25 µM), a well known antioxidant, distinctly reduced the level of apoptotic markers. The obtained results indicate that Hcys and its thiolactone may promote in vitro apoptotic events in human gel-filtered platelets.

  9. [Morphometrical parameters of placenta and condition of NO-dependent mechanisms in fetuses during normal pregnancy and with damages of uteroplacental blood circulation at white rats].

    PubMed

    Nazorov, S B; Ivanova, A S; Novikov, A A

    2012-01-01

    The purpose of paper is an estimation of morphometric parameters and status of NO-dependent mechanisms of embryos placenta of white rats in normal conditions, experimental disturbance of the utero-placental circulation and after the nitric oxide donator "Deponit-10" using. The volume density of blood vessels in the placenta and placental vascular exchange area significantly increases under chronic intrauterine hypoxia. The donator of nitric oxide has a positive effect on morphometric parameters of the placenta, provides effective adaptation of feto-placental blood flow to hypoxia and could be useful for clinical practice.

  10. Identification of carcinoembryonic antigen-producing cells circulating in the blood of patients with colorectal carcinoma by reverse transcriptase polymerase chain reaction.

    PubMed Central

    Jonas, S; Windeatt, S; O-Boateng, A; Fordy, C; Allen-Mersh, T G

    1996-01-01

    BACKGROUND: Application of the reverse transcriptase polymerase chain reaction (RT-PCR) to identification of circulating tumour cells in colorectal cancer. AIMS: To assess whether circulating malignant cells in patients with colorectal liver metastasis could be identified by RT-PCR recognition of mRNA coding for the tumour marker carcinoembryonic antigen (CEA). PATIENTS: A total of 31 with colorectal liver metastases and 22 no-cancer controls. METHODS: Specific cDNA primers for CEA transcripts were used to apply RT-PCR to tissue biopsy specimens, colon carcinoma cell lines, and peripheral blood samples from patients with colorectal liver metastases. A strongly CEA-expressive HT115 colorectal carcinoma cell line was used to spike blood samples from no-cancer control subjects. RESULTS: The limit for detection of CEA cDNA by Southern blotting using HT115 cells was 50 cells per 14 ml of spiked blood. There was a significant difference (p = 0.007) in RT-PCR positive expression between patients with liver metastasis (26/31) compared with controls (5/22). There was no significant relation between the prevalence of CEA cDNA amplification and serum CEA level or metastasis volume in patients with liver metastasis. CONCLUSIONS: This is the first study to suggest that identification of circulating colorectal cancer cells using RT-PCR for detection of CEA cDNA is feasible. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:9014772

  11. Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse.

    PubMed

    Chatterjee, Sreoshi; Bhardwaj, Nitin; Saxena, Rajiv K

    2016-01-01

    Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA) in C57BL/6 mice after 5-6 weeks. Using the double in vivo biotinylation (DIB) technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS) were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline). Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA.

  12. [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.

  13. Xanthine dehydrogenase-1 silencing in Aedes aegypti mosquitoes promotes a blood feeding-induced adulticidal activity.

    PubMed

    Isoe, Jun; Petchampai, Natthida; Isoe, Yurika E; Co, Katrina; Mazzalupo, Stacy; Scaraffia, Patricia Y

    2017-02-08

    Aedesaegypti has 2 genes encoding xanthine dehydrogenase (XDH). We analyzed XDH1 and XDH2 gene expression by real-time quantitative PCR in tissues from sugar- and blood-fed females. Differential XDH1 and XDH2 gene expression was observed in tissues dissected throughout a time course. We next exposed females to blood meals supplemented with allopurinol, a well-characterized XDH inhibitor. We also tested the effects of injecting double-stranded RNA (dsRNA) against XDH1, XDH2, or both. Disruption of XDH by allopurinol or XDH1 by RNA interference significantly affected mosquito survival, causing a disruption in blood digestion, excretion, oviposition, and reproduction. XDH1-deficient mosquitoes showed a persistence of serine proteases in the midgut at 48 h after blood feeding and a reduction in the uptake of vitellogenin by the ovaries. Surprisingly, analysis of the fat body from dsRNA-XDH1-injected mosquitoes fell into 2 groups: one group was characterized by a reduction of the XDH1 transcript, whereas the other group was characterized by an up-regulation of several transcripts including XDH1, glutamine synthetase, alanine aminotransferase, catalase, superoxide dismutase, ornithine decarboxylase, glutamate receptor, and ammonia transporter. Our data demonstrate that XDH1 plays an essential role and that XDH1 has the potential to be used as a metabolic target for Ae.aegypti vector control.-Isoe, J., Petchampai, N., Isoe, Y. E., Co, K., Mazzalupo, S., Scaraffia, P. Y. Xanthine dehydrogenase-1 silencing in Aedes aegypti mosquitoes promotes a blood feeding-induced adulticidal activity.

  14. Smooth muscle progenitor cells from peripheral blood promote the neovascularization of endothelial colony-forming cells

    SciTech Connect

    Joo, Hyung Joon; Seo, Ha-Rim; Jeong, Hyo Eun; Choi, Seung-Cheol; Park, Jae Hyung; Yu, Cheol Woong; Hong, Soon Jun; Chung, Seok; Lim, Do-Sun

    2014-07-11

    Highlights: • Two distinct vascular progenitor cells are induced from adult peripheral blood. • ECFCs induce vascular structures in vitro and in vivo. • SMPCs augment the in vitro and in vivo angiogenic potential of ECFCs. • Both cell types have synergistic therapeutic potential in ischemic hindlimb model. - Abstract: Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelial cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.

  15. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance

    PubMed Central

    Sayers, Sophie R.; Reimann, Frank; Gribble, Fiona M.; Parker, Helen; Zac-Varghese, Sagen; Bloom, Stephen R.; Foretz, Marc; Viollet, Benoit; Rutter, Guy A.

    2016-01-01

    Background Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1) in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK) in these cells. Method Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre) to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay. Results Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01) in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01) and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01) GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01). Conclusion AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes. PMID:27010458

  16. Distinctions Among Circulating Antibody Secreting Cell Populations, Including B-1 Cells, in Human Adult Peripheral Blood1

    PubMed Central

    Quách, Tâm D.; Rodríguez-Zhurbenko, Nely; Hopkins, Thomas J.; Guo, Xiaoti; Vázquez, Ana María Hernández; Li, Wentian; Rothstein, Thomas L.

    2015-01-01

    Human antibody secreting cell (ASC) populations in circulation are not well studied. In addition to B-1 (CD20+CD27+CD38lo/intCD43+) cell and the conventional plasmablast (CD20-CD27hiCD38hi) cell populations, here we identified a novel B cell population termed 20+38hi B cells (CD20+CD27hiCD38hi) that spontaneously secretes antibody. At steady state, 20+38hi B cells are distinct from plasmablasts on the basis of CD20 expression, amount of antibody production, frequency of mutation, and diversity of B cell receptor repertoire. However, cytokine treatment of 20+38hi B cells induces loss of CD20 and acquisition of CD138, suggesting that 20+38hi B cells are precursors to plasmablasts, or pre-plasmablasts. We then evaluated similarities and differences between CD20+CD27+CD38lo/intCD43+ B-1 cells, CD20+CD27hiCD38hi 20+38hi B cells, CD20-CD27hiCD38hi plasmablasts, and CD20+CD27+CD38lo/intCD43- memory B cells. We found that B-1 cells differ from 20+38hi B cells and plasmablasts in numbers of ways, including antigen expression, morphological appearance, transcriptional profiling, antibody skewing, antibody repertoire, and secretory response to stimulation. In terms of gene expression, B-1 cells align more closely with memory B cells than with 20+38hi B cells or plasmablasts, but differ in that memory B cells do not express antibody secretion related genes. We found that, B-1 cell antibodies utilize Vh4-34, which is often associated with autoreactivity, 3 to 6-fold more often than other B cell populations. Along with selective production of IgM anti-PC, this data suggests that human B-1 cells might be preferentially selected for autoreactivity/natural-specificity. In sum, our results indicate that human healthy adult peripheral blood at steady state consists of 3 distinct ASC populations. PMID:26740107

  17. Decreased expression of circulating microRNA-126 in patients with type 2 diabetic nephropathy: A potential blood-based biomarker

    PubMed Central

    Al-Kafaji, Ghada; Al-Mahroos, Ghazi; Al-Muhtaresh, Haifa Abdulla; Skrypnyk, Cristina; Sabry, Mohamed Abdalla; Ramadan, Ahmad R.

    2016-01-01

    Circulating microRNAs (miRNAs) have been proposed as promising biomarkers for multiple diseases. miR-126 is reported to be associated with type 2 diabetes mellitus (T2D), diabetic nephropathy (DN) and end stage renal disease. The aim of this study was to investigate the expression of circulating miR-126 and to assess its potential as a blood-based biomarker for DN in T2D patients. In 52 patients with T2D without history of DN (with noromoalbuminuria), 50 patients with T2D and DN (29 with microalbuminuria and 21 with macroalbuminuria), and 50 non-diabetic healthy controls, the expression of circulating miR-126 in peripheral whole blood was evaluated by quantitative polymerase chain reaction. The expression levels of circulating miR-126 were significantly decreased in T2D patients and further decreased in DN patients compared with those in the controls. Multivariate logistic regression analysis confirmed the independent association of lower miR-126 levels with T2D [adjusted odds ratio (OR), 0.797; 95% confidence interval (CI), 0.613–0.960] and DN (adjusted OR, 0.513; 95% CI, 0.371–0.708). miR-126 levels were associated with the degree of albuminuria and showed significantly low expression in DN patients with microalbuminuria (adjusted OR, 0.781; 95% CI; 0.698–0.952) and further lower expression in DN patients with macroalbuminuria (adjusted OR, 0.433; 95% CI, 0.299–0.701), respectively compared with T2D patients with normoalbuminuria. miR-126 levels negatively correlated with albuminuria positively with glomerular filtration rate (P<0.05), and in addition, negatively correlated with fasting glucose, glycated hemoglobin, triglyceride and LDL (P<0.05). Stepwise multiple regression analysis identified albuminuria as a significant predictor of miR-126 (P<0.001). miR-126 in peripheral blood yielded area under the receiver operating characteristic curves of 0.854 (95% CI, 0.779–0.929) and 0.959 (95% CI, 0.916–1.000) in the differentiation of DN patients from T2

  18. Decreased expression of circulating microRNA-126 in patients with type 2 diabetic nephropathy: A potential blood-based biomarker.

    PubMed

    Al-Kafaji, Ghada; Al-Mahroos, Ghazi; Al-Muhtaresh, Haifa Abdulla; Skrypnyk, Cristina; Sabry, Mohamed Abdalla; Ramadan, Ahmad R

    2016-08-01

    Circulating microRNAs (miRNAs) have been proposed as promising biomarkers for multiple diseases. miR-126 is reported to be associated with type 2 diabetes mellitus (T2D), diabetic nephropathy (DN) and end stage renal disease. The aim of this study was to investigate the expression of circulating miR-126 and to assess its potential as a blood-based biomarker for DN in T2D patients. In 52 patients with T2D without history of DN (with noromoalbuminuria), 50 patients with T2D and DN (29 with microalbuminuria and 21 with macroalbuminuria), and 50 non-diabetic healthy controls, the expression of circulating miR-126 in peripheral whole blood was evaluated by quantitative polymerase chain reaction. The expression levels of circulating miR-126 were significantly decreased in T2D patients and further decreased in DN patients compared with those in the controls. Multivariate logistic regression analysis confirmed the independent association of lower miR-126 levels with T2D [adjusted odds ratio (OR), 0.797; 95% confidence interval (CI), 0.613-0.960] and DN (adjusted OR, 0.513; 95% CI, 0.371-0.708). miR-126 levels were associated with the degree of albuminuria and showed significantly low expression in DN patients with microalbuminuria (adjusted OR, 0.781; 95% CI; 0.698-0.952) and further lower expression in DN patients with macroalbuminuria (adjusted OR, 0.433; 95% CI, 0.299-0.701), respectively compared with T2D patients with normoalbuminuria. miR-126 levels negatively correlated with albuminuria positively with glomerular filtration rate (P<0.05), and in addition, negatively correlated with fasting glucose, glycated hemoglobin, triglyceride and LDL (P<0.05). Stepwise multiple regression analysis identified albuminuria as a significant predictor of miR-126 (P<0.001). miR-126 in peripheral blood yielded area under the receiver operating characteristic curves of 0.854 (95% CI, 0.779-0.929) and 0.959 (95% CI, 0.916-1.000) in the differentiation of DN patients from T2D patients

  19. High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin

    PubMed Central

    Fu, Afu; Ma, Shijun; Wei, Na; Xuan Tan, Blanche Xiao; Tan, Ern Yu; Luo, Kathy Qian

    2016-01-01

    Understanding the survival mechanism of metastatic cancer cells in circulation will provide new perspectives on metastasis prevention and also shed new light on metastasis-derived drug resistance. In this study, we made it feasible to detect apoptosis of circulating tumor cells (CTCs) in real-time by integrating a fluorescence resonance energy transfer (FRET)-based caspase sensor into one in vitro microfluidic circulatory system, and two in vivo models: zebrafish circulation and mouse lung metastatic model. Our study demonstrated that fluid shear stresses triggered apoptosis of breast cancer cells in circulation by elevating the mitochondrial production of the primary free radical, superoxide anion. Cancer cells with high levels of manganese superoxide dismutase (MnSOD) exhibited stronger resistance to shear force-induced apoptosis and formed more lung metastases in mice. These metastasized cells further displayed higher resistance to chemotherapeutic agent doxorubicin, which also generates superoxide in mitochondria. Specific siRNA-mediated MnSOD knockdown reversed all three phenotypes. Our findings therefore suggest that MnSOD plays an important integrative role in supporting cancer cell survival in circulation, metastasis, and doxorubicin resistance. MnSOD can serve as a new biomarker for identifying metastatic CTCs and a novel therapeutic target for inhibiting metastasis and destroying doxorubicin-resistant breast cancer cells. PMID:27384484

  20. The effect of smoking on MAOA promoter methylation in DNA prepared from lymphoblasts and whole blood.

    PubMed

    Philibert, Robert A; Beach, Steven R H; Gunter, Tracy D; Brody, Gene H; Madan, Anup; Gerrard, Meg

    2010-03-05

    Prior work using lymphoblast DNA prepared from 192 subjects from the Iowa Adoption Studies (IAS) demonstrated that decreased MAOA promoter methylation was associated with lifetime symptom count for nicotine dependence (ND) and provided suggestive evidence that the amount of methylation is genotype dependent. In the current investigation, we replicate and extend these prior findings in three ways using another 289 IAS subjects and the same methodologies. First, we show that methylation is dependent on current smoking status. Second, we introduce a factor analytic approach to DNA methylation, highlighting three distinct regions of the promoter that may function in somewhat different ways for males and females. Third, we directly compare the methylation signatures in DNA prepared from whole blood and lymphoblasts from a subset of these subjects and provide suggestive evidence favoring the use of lymphoblast DNA. We conclude that smoking reliably decreases MAOA methylation, but exact characterization of effects on level of methylation depend on genotype, smoking history, current smoking status, gender, and region of the promoter-associated CpG Island examined.

  1. Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination

    PubMed Central

    Zheng, Yu; Miyamoto, David T.; Wittner, Ben S.; Sullivan, James P.; Aceto, Nicola; Jordan, Nicole Vincent; Yu, Min; Karabacak, Nezihi Murat; Comaills, Valentine; Morris, Robert; Desai, Rushil; Desai, Niyati; Emmons, Erin; Milner, John D.; Lee, Richard J.; Wu, Chin-Lee; Sequist, Lecia V.; Haas, Wilhelm; Ting, David T.; Toner, Mehmet; Ramaswamy, Sridhar; Maheswaran, Shyamala; Haber, Daniel A.

    2017-01-01

    Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4. Depletion of HBB in CTC-derived cultures has minimal effects on primary tumour growth, but it greatly increases apoptosis following ROS exposure, and dramatically reduces CTC-derived lung metastases. These effects are reversed by the anti-oxidant N-Acetyl Cysteine. Conversely, overexpression of HBB is sufficient to suppress intracellular ROS within CTCs. Altogether, these observations suggest that β-globin is selectively deregulated in cancer cells, mediating a cytoprotective effect during blood-borne metastasis. PMID:28181495

  2. [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.

  3. 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.

  4. Quantitative analysis of follistatin (FST) promoter methylation in peripheral blood of patients with polycystic ovary syndrome.

    PubMed

    Sang, Qing; Zhang, Shaozhen; Zou, Shien; Wang, Huan; Feng, Ruizhi; Li, Qiaoli; Jin, Li; He, Lin; Xing, Qinghe; Wang, Lei

    2013-02-01

    Epigenetic mechanisms may contribute to polycystic ovary syndrome (PCOS). To date, however, no studies have associated CpG methylation levels of any candidate gene with PCOS susceptibility. Follistatin (FST), an activin-binding protein, is expressed in numerous tissues and is shown to have linkage with PCOS. However, results from case-control association analyses between this gene and PCOS are inconsistent. Thus, this study investigated possible association of methylation levels in the promoter and 5'-untranscribed region (UTR) of the FST gene with PCOS incidence in peripheral blood leukocytes and endometrial tissue. Using mass array quantitative methylation analysis, first the 5'-UTR methylation in FST was analysed in 130 PCOS patients and 120 controls. The methylation level of the FST gene was further studied in endometrium from 24 controls and 24 PCOS patients. This study demonstrates that methylation levels of CpG sites in the FST promoter and 5'-UTR are not associated with PCOS. Nonetheless, this was the first study to quantitatively evaluate the methylation levels of a candidate gene in association with PCOS. Further studies should be performed to examine methylation in other candidate genes. Understanding the epigenetic mechanisms involved in PCOS may yield new insights into the pathophysiology of the disorder. Animal models demonstrate that epigenetic reprogramming may contribute to polycystic ovary syndrome (PCOS). To date, however, no studies have associated CpG methylation levels of any candidate gene with PCOS susceptibility. Follistatin (FST), an activin-binding protein, is expressed in numerous tissues and is a PCOS candidate gene. However, results from association analyses between this gene and PCOS are inconsistent. Thus, we investigated possible association of methylation levels in the promoter and 5'-UTR of the FST gene with PCOS incidence in peripheral blood leukocytes and endometrial tissue. Using mass array quantitative methylation analysis, we

  5. Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption.

    PubMed

    Zhang, Susu; Dong, Hongquan; Zhang, Xiang; Li, Nana; Sun, Jie; Qian, Yanning

    2016-02-01

    Trauma induced neuroinflammation plays a key role in the development of postoperative cognitive dysfunction (POCD). The blood-brain barrier (BBB), a highly specialized endothelial layer, is exquisitely sensitive to inflammatory insults, which can result in numerous neurocognitive syndromes. While brain mast cells are the "first responder" in the injury, the functional interactions between mast cells and the BBB remain poorly understood. Our results demonstrate that tibial fracture surgery can induce cognitive impairment relating to an inflammatory response and destabilization of the BBB. Disodium cromoglycate (cromolyn)--which acts as a mast cell stabilizer--inhibited this effect. Specifically, cromolyn resulted in ameliorated cognitive ability, decrease of inflammatory cytokines and increase of BBB stability. Taken together, these results suggest that activated mast cells contributed to central nervous system inflammation and cognitive dysfunction by promoting BBB disruption, and interactions between mast cells and the BBB could constitute a new and unique therapeutic target for POCD.

  6. Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse

    PubMed Central

    Chatterjee, Sreoshi; Bhardwaj, Nitin; Saxena, Rajiv K.

    2016-01-01

    Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA) in C57BL/6 mice after 5–6 weeks. Using the double in vivo biotinylation (DIB) technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS) were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline). Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA. PMID:27870894

  7. Blood

    MedlinePlus

    ... The 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. Red ...

  8. 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.

  9. Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development.

    PubMed

    Fernandes, Luciana R; Ribeiro, Ana Cecília C; Segatto, Marcela; Santos, Luís Felipe F F; Amaral, Joana; Portugal, Luciane R; Leite, Jacqueline I A

    2013-01-01

    Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages.

  10. Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development

    PubMed Central

    Fernandes, Luciana R.; Ribeiro, Ana Cecília C.; Segatto, Marcela; Santos, Luís Felipe F. F.; Amaral, Joana; Portugal, Luciane R.; Leite, Jacqueline I. A.

    2013-01-01

    Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages. PMID:23710353

  11. Targeting Transporters: Promoting Blood-Brain Barrier Repair in Response to Oxidative Stress Injury

    PubMed Central

    Ronaldson, Patrick T.; Davis, Thomas P.

    2015-01-01

    The blood-brain barrier (BBB) is a physical and biochemical barrier that precisely regulates the ability of endogenous and exogenous substances to accumulate within brain tissue. It possesses structural and biochemical features (i.e., tight junction and adherens junction protein complexes, influx and efflux transporters) that work in concert to control solute permeation. Oxidative stress, a critical component of several diseases including cerebral hypoxia/ischemia and peripheral inflammatory pain, can cause considerable injury to the BBB and lead to significant CNS pathology. This suggests a critical need for novel therapeutic approaches that can protect the BBB in diseases with an oxidative stress component. Recent studies have identified molecular targets (i.e., endogenous transporters, intracellular signaling systems) that can be exploited for optimization of endothelial drug delivery or for control of transport of endogenous substrates such as the antioxidant glutathione (GSH). In particular, targeting transporters offers a unique approach to protect BBB integrity by promoting repair of cell-cell interactions at the level of the brain microvascular endothelium. This review summarizes current knowledge in this area and emphasizes those targets that present considerable opportunity for providing BBB protection and/or promoting BBB repair in the setting of oxidative stress. PMID:25796436

  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. Mathematical modeling of gravitational effects on the circulation: importance of the time course of venous pooling and blood volume changes in the lungs.

    PubMed

    van Heusden, K; Gisolf, J; Stok, W J; Dijkstra, S; Karemaker, J M

    2006-11-01

    A dip in blood pressure (BP) in response to head-up tilt (HUT) or active standing might be due to rapid pooling in the veins below the heart (preload) or muscle activation-induced drop in systemic vascular resistance (afterload). We hypothesized that, in the cardiovascular response to passive HUT, where, in contrast to active standing, little BP dip is observed, features affecting the preload play a key role. We developed a baroreflex model combined with a lumped-parameter model of the circulation, including viscoelastic stress-relaxation of the systemic veins. Cardiac contraction is modeled using the varying-elastance concept. Gravity affects not only the systemic, but also the pulmonary, circulation. In accordance with the experimental results, model simulations do not show a BP dip on HUT; the tilt-back response is also realistic. If it is assumed that venous capacities are steady-state values, the introduction of stress-relaxation initially reduces venous pooling. The resulting time course of venous pooling is comparable to measured impedance changes. When venous pressure-volume dynamics are neglected, rapid (completed within 30 s) venous pooling leads to a drop in BP. The direct effect of gravity on the pulmonary circulation influences the BP response in the first approximately 5 s after HUT and tilt back. In conclusion, the initial BP response to HUT is mainly determined by the response of the venous system. The time course of lower body pooling is essential in understanding the response to passive HUT.

  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. ZnO-Based Microfluidic pH Sensor: A Versatile Approach for Quick Recognition of Circulating Tumor Cells in Blood.

    PubMed

    Mani, Ganesh Kumar; Morohoshi, Madoka; Yasoda, Yutaka; Yokoyama, Sho; Kimura, Hiroshi; Tsuchiya, Kazuyoshi

    2017-02-15

    The present study is concerned about the development of highly sensitive and stable microfluidic pH sensor for possible identification of circulating tumor cells (CTCs) in blood. The precise pH measurements between silver-silver chloride (Ag/AgCl) reference electrode and zinc oxide (ZnO) working electrode have been investigated in the microfluidic device. Since there is a direct link between pH and cancer cells, the developed device is one of the valuable tools to examine circulating tumor cells (CTCs) in blood. The ZnO-based working electrode was deposited by radio frequency (rf) sputtering technique. The potential voltage difference between the working and reference electrodes (Ag/AgCl) is evaluated on the microfluidic device. The ideal Nernstian response of -43.71165 mV/pH was achieved along with high stability and quick response time. Finally, to evaluate the real time capability of the developed microfluidic device, in vitro testing was done with A549, A7r5, and MDCK cells.

  16. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis.

    PubMed

    Jin, Junhua; Niu, Xiaojuan; Zou, Lihui; Li, Lin; Li, Shugang; Han, Jingli; Zhang, Peiying; Song, Jinghai; Xiao, Fei

    2016-08-01

    Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis.

  17. Albumin infusion may deleteriously promote extracellular fluid overload without improving circulating hypovolemia in patients of advanced cirrhosis with diabetes mellitus and sepsis.

    PubMed

    Kumar, Ramesh; Kumar, Sachin; Lata, Suman

    2013-04-01

    In patients with liver cirrhosis, albumin is given to improve relative hypovolemia caused by marked splanchnic arteriolar vasodilatation. However, the volume effect of albumin is not predictable and depends also on capillary permeability, hydrostatic pressure and lymphatic ability to re-circulate albumin from interstitium to plasma. In patients with decompensated cirrhosis, the capillary permeability is increased, hydrostatic pressure is higher, and the lymphatics functions are deficient. Hence the albumin molecules are more likely to be extravasated rapidly into the interstitium and are subsequently less likely to be re-circulated back into the plasma. This would not only fail to correct circulating hypovolemia, the purpose for which it is given, but also would favor development of reverse colloid oncotic pressure and fluid movement out of the capillaries leading to development of edema. Thus, anything else which could further increase capillary permeability or hydrostatic pressure in cirrhotic patients might create more problems with albumin infusion. An increased capillary permeability is the hallmark of diabetes mellitus. Furthermore, diabetes mellitus may worsen immunodepression in cirrhotic patients thus increasing the incidence of severe infections which may further have a deleterious effect on hemodynamics and capillary permeability. A diabetic patient with advanced cirrhosis and sepsis usually has markedly increased capillary permeability, high hydrostatic pressure due to hyperdynamic circulation, and compromised lymphatic drainage capacity. Hence, using albumin infusion in them would not only fail to improve relative hypovolemia, but also would deleteriously promote extravascular accumulation of fluid, which might impair the functions of many vital organs. However, the efficacy and safety of albumin infusion in diabetic patients with advanced cirrhosis and sepsis is not known. Such data can have a great clinical implication and would necessitate search of

  18. Blood

    MedlinePlus

    ... that die or are lost from the body. White Blood Cells White blood cells (WBCs, and also ... of severe pain. previous continue Diseases of the White Blood Cells Neutropenia (pronounced: new-truh-PEE-nee- ...

  19. Comparison of methods for circulating cell-free DNA isolation using blood from cancer patients: impact on biomarker testing

    PubMed Central

    Pérez-Barrios, Clara; Nieto-Alcolado, Irene; Torrente, María; Jiménez-Sánchez, Carolina; Calvo, Virginia; Gutierrez-Sanz, Lourdes; Palka, Magda; Donoso-Navarro, Encarnación; Provencio, Mariano

    2016-01-01

    Background The implementation of liquid biopsy for biomarker testing and response to treatment monitoring in cancer patients would presumable increase laboratory throughput, requiring the development of automated methods for circulating free DNA (cfDNA) isolation. Methods The present study compares the MagNA Pure Compact (MPC) Nucleic Acid Isolation Kit I and Maxwell® RSC (MR) ccfDNA Plasma Kit and the later with QIAamp Circulating Nucleid Acid (QCNA) Kit using 57 plasma samples from cancer patients. cfDNA concentration was measured using the Qubit fluorometer. DNA fragments lengt were assessed using the Agilent 2100 Bioanalyzer. Circulating tumor DNA (ctDNA) was quantified by digital PCR (dPCR). Results Firstly, we observed that MPC method significantly extracted less cfDNA than MR (P<0.0001). However, there were no significant differences in extraction yields of QCNA and MR kits. cfDNA isolation yield was also associated with tumor stage but not with tumor location. Secondly, an oligonucleosomal DNA ladder pattern was observed in 88% of the samples and significant differences in the recovery of mono-, di- and tri-nucleosomes DNA fragments were observed between MPC and MR methodologies. Finally, tumor mutation quantification on cfDNA was performed on 38 paired samples using digital PCR. Mutant allele fractions (MAFs) between paired samples were not significantly different. Conclusions Methods for isolation of cfDNA can affect DNA yield and molecular weight fractions recovery. These observations should be taken into account for cfDNA analysis in routine clinical practice. PMID:28149760

  20. 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.

  1. 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.

  2. 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

  3. Methamphetamine-induced nitric oxide promotes vesicular transport in blood-brain barrier endothelial cells.

    PubMed

    Martins, Tânia; Burgoyne, Thomas; Kenny, Bridget-Ann; Hudson, Natalie; Futter, Clare E; Ambrósio, António F; Silva, Ana P; Greenwood, John; Turowski, Patric

    2013-02-01

    Methamphetamine's (METH) neurotoxicity is thought to be in part due to its ability to induce blood-brain barrier (BBB) dysfunction. Here, we investigated the effect of METH on barrier properties of cultured rat primary brain microvascular endothelial cells (BMVECs). Transendothelial flux doubled in response to METH, irrespective of the size of tracer used. At the same time, transendothelial electrical resistance was unchanged as was the ultrastructural appearance of inter-endothelial junctions and the distribution of key junction proteins, suggesting that METH promoted vesicular but not junctional transport. Indeed, METH significantly increased uptake of horseradish peroxidase into vesicular structures. METH also enhanced transendothelial migration of lymphocytes indicating that the endothelial barrier against both molecules and cells was compromised. Barrier breakdown was only observed in response to METH at low micromolar concentrations, with enhanced vesicular uptake peaking at 1 μM METH. The BMVEC response to METH also involved rapid activation of endothelial nitric oxide synthase and its inhibition abrogated METH-induced permeability and lymphocyte migration, indicating that nitric oxide was a key mediator of BBB disruption in response to METH. This study underlines the key role of nitric oxide in BBB function and describes a novel mechanism of drug-induced fluid-phase transcytosis at the BBB.

  4. Identification of six potential markers for the detection of circulating canine mammary tumour cells in the peripheral blood identified by microarray analysis.

    PubMed

    da Costa, A; Lenze, D; Hummel, M; Kohn, B; Gruber, A D; Klopfleisch, R

    2012-01-01

    The presence of circulating tumour cells (CTCs) in the peripheral blood is a prognostic factor for survival of human breast cancer patients. CTCs in the peripheral blood of dogs with mammary tumours have not been reported definitively. The present pilot study identifies mRNA markers for CTCs by comparing the transcriptome of canine mammary carcinoma cell lines CMM26 and CMM115 and peripheral blood leucocytes (PBLs). Genes with a 200-fold or higher mRNA expression in carcinoma cell lines were tested for specificity and sensitivity to detect CTCs using reverse transcriptase polymerase chain reaction (PCR). Six mRNA markers, AGR2, ATP8B1, CRYAB, F3 IRX3 and SLC1A1 were expressed in cell lines, but not PBL. All PCRs were able to detect one carcinoma cell admixed in 10(6) or more PBLs. The six mRNA markers may be suitable for detection of canine mammary CTCs and allow the analysis of their spatiotemporal distribution in dogs with mammary tumours.

  5. 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

  6. Promoter hypermethylation of the tumor-suppressor genes ITIH5, DKK3, and RASSF1A as novel biomarkers for blood-based breast cancer screening

    PubMed Central

    2013-01-01

    Introduction For early detection of breast cancer, the development of robust blood-based biomarkers that accurately reflect the host tumor is mandatory. We investigated DNA methylation in circulating free DNA (cfDNA) from blood of breast cancer patients and matched controls to establish a biomarker panel potentially useful for early detection of breast cancer. Methods We examined promoter methylation of seven putative tumor-suppressor genes (SFRP1, SFRP2, SFRP5, ITIH5, WIF1, DKK3, and RASSF1A) in cfDNA extracted from serum. Clinical performance was first determined in a test set (n = 261 sera). In an independent validation set (n = 343 sera), we validated the most promising genes for further use in early breast cancer detection. Sera from 59 benign breast disease and 58 colon cancer patients were included for additional specificity testing. Results Based on the test set, we determined ITIH5 and DKK3 promoter methylation as candidate biomarkers with the best sensitivity and specificity. In both the test and validation set combined, ITIH5 and DKK3 methylation achieved 41% sensitivity with a specificity of 93% and 100% in healthy and benign disease controls, respectively. Combination of these genes with RASSF1A methylation increased the sensitivity to 67% with a specificity of 69% and 82% in healthy controls and benign disease controls, respectively. Conclusions Tumor-specific methylation of the three-gene panel (ITIH5, DKK3, and RASSF1A) might be a valuable biomarker for the early detection of breast cancer. PMID:23320751

  7. 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.

  8. Effectiveness of physical activity promotion in blood pressure and blood sugar reduction: A community–based intervention study in rural south India

    PubMed Central

    Lakshminarayanan, Subitha; Bala, Soudarssanane M.; Ramanujam, Murugesan; Kannan, G.

    2012-01-01

    Context: Physical activity of moderate intensity for 30 minutes a day, on most days substantially reduces the risk of many chronic diseases. Aim: To assess the effect of regular physical activity on blood pressure and blood sugar levels in a rural Indian community Settings and Design: This community-based study was carried out in Periakattupalayam and Rangareddipalayam in south India, with 485 subjects, aged 20 to 49 years. Materials and Methods: The study was done in five phases: Awareness campaign, baseline assessment of participants, intervention phase (10 weeks), interim, and final assessment. Physical activity of moderate intensity (brisk walking for 30 minutes on four days / week) was promoted by forming 30 small walking groups, in a home-based setting, with professional supervision. Village leaders and Self-Help Group members were the resource people for the promotion of physical activity. Statistical Analysis: Analysis was done by using paired ‘t’ test; the ‘Intention-to-Treat’ approach was utilized for the interpretation of the findings of the study. Results: Of the 485 subjects, 265 (54.6%) complied with walking on more than four days / week, while 156 (32.2%) walked on one to four days / week, and 64 (13.2%) dropped out during the intervention period. This study has shown that a 10-week intervention to promote physical activity was effective in significantly decreasing the population's BP by 1.56 / 0.74 mm Hg, fasting blood sugar levels by 2.82 mg%, body weight by 0.17 kg, and BMI by 0.06 kg / m2. Conclusions: This study has proved the functional feasibility of enabling people to undertake physical activity in a rural Indian community, and the effectiveness of using physical activity, to significantly reduce the population's mean BP and blood sugar levels. PMID:22870410

  9. Preoperative liver dysfunction influences blood product administration and alterations in circulating haemostatic markers following ventricular assist device implantation

    PubMed Central

    Woolley, Joshua R.; Kormos, Robert L.; Teuteberg, Jeffrey J.; Bermudez, Christian A.; Bhama, Jay K.; Lockard, Kathleen L.; Kunz, Nicole M.; Wagner, William R.

    2015-01-01

    OBJECTIVES Preoperative liver dysfunction may influence haemostasis following ventricular assist device (VAD) implantation. The Model for End-stage Liver Disease (MELD) score was assessed as a predictor of bleeding and levels of haemostatic markers in patients with currently utilized VADs. METHODS Sixty-three patients (31 HeartMate II, 15 HeartWare, 17 Thoratec paracorporeal ventricular assist device) implanted 2001–11 were analysed for preoperative liver dysfunction (MELD) and blood product administration. Of these patients, 21 had additional blood drawn to measure haemostatic marker levels. Cohorts were defined based on high (≥18.0, n = 7) and low (<18.0, n = 14) preoperative MELD scores. RESULTS MELD score was positively correlated with postoperative administration of red blood cell (RBC), platelet, plasma and total blood product units (TBPU) , as well as chest tube drainage and cardiopulmonary bypass time. Age and MELD were preoperative predictors of TBPU by multivariate analysis. The high-MELD cohort had higher administration of TBPU, RBC and platelet units and chest tube drainage postimplant. Similarly, patients who experienced at least one bleeding adverse event were more likely to have had a high preoperative MELD. The high-MELD group exhibited different temporal trends in F1 + 2 levels and platelet counts to postoperative day (POD) 55. D-dimer levels in high-MELD patients became elevated versus those for low-MELD patients on POD 55. CONCLUSIONS Preoperative MELD score predicts postoperative bleeding in contemporary VADs. Preoperative liver dysfunction may also alter postoperative subclinical haemostasis through different temporal trends of thrombin generation and platelet counts, as well as protracted fibrinolysis. PMID:24810756

  10. Speech therapy changes blood circulation and oxygenation in the brain and muscle: a near-infrared spectrophotometry study.

    PubMed

    Wolf, Martin; von Bonin, Dietrich; Wolf, Ursula

    2011-01-01

    Recently it has been shown that artistic speech therapy (AST) has effects on heart rate variability. The aim of this pilot study was to investigate whether AST also affects hemodynamics and tissue oxygenation in the brain and skeletal muscle measured by near infrared spectrophotometry(NIRS). The results show that ATS has effects on important physiological parameters, i.e., it leads to a decrease in cerebral blood flow during recitation and to brain activation thereafter.

  11. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Association of circulating levels of RANTES and -403G/A promoter polymorphism to acute heart failure after STEMI and to cardiogenic shock.

    PubMed

    Lipkova, Jolana; Parenica, Jiri; Duris, Kamil; Helanova, Katerina; Tomandl, Josef; Kubkova, Lenka; Vasku, Anna; Goldbergova Pavkova, Monika

    2015-08-01

    Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES -403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES -403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES -403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction.

  17. Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells

    PubMed Central

    Fehm, Tanja; Hoffmann, Oliver; Aktas, Bahriye; Becker, Sven; Solomayer, Erich F; Wallwiener, Diethelm; Kimmig, Rainer; Kasimir-Bauer, Sabine

    2009-01-01

    Introduction The role of circulating tumor cells (CTCs) in blood of primary breast cancer patients is still under investigation. We evaluated the incidence of CTCs in blood, we evaluated the correlation between CTCs and disseminated tumor cells (DTCs) in the bone marrow (BM), and we characterized CTCs for the expression of HER2, the estrogen receptor (ER) and the progesterone receptor (PR). Methods Blood of 431 patients with primary breast cancer were analyzed for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer™ (AdnaGen AG, Germany). Expression of the ER and PR was assessed in an additional RT-PCR. BM aspirates from 414 patients were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Results DTCs were found in 107/414 patients (24%), CTCs were detected in 58/431 (13%) patients. DTCs were associated with PR status of the primary tumor (P = 0.04) and CTCs significantly correlated with nodal status (P = 0.04), ER (P = 0.05), and PR (P = 0.01). DTCs in the BM weakly correlated with CTCs (P = 0.05) in blood. Interestingly, the spread of CTCs was mostly found in triple-negative tumors (P = 0.01) and CTCs in general were mostly found to be triple-negative regardless of the ER, PR and HER2 status of the primary tumor. Conclusions (1) Due to the weak concordance between CTCs and DTCs the clinical relevance may be different. (2) The biology of the primary tumor seems to direct the spread of CTCs. (3) Since the expression profile between CTCs and the primary tumor differs, the consequence for the selection of adjuvant treatment has to be evaluated. PMID:19664291

  18. Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma

    PubMed Central

    Yu, Xin-Min; Wu, Yi-Chen; Liu, Xiang; Huang, Xian-Cong; Hou, Xiu-Xiu; Wang, Jiu-Li; Cheng, Xiang-Liu; Mao, Wei-Min; Ling, Zhi-Qiang

    2016-01-01

    Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients. PMID:27827952

  19. Changes in skin blood flow during the menstrual cycle: the influence of the menstrual cycle on the peripheral circulation in healthy female volunteers.

    PubMed

    Bartelink, M L; Wollersheim, H; Theeuwes, A; van Duren, D; Thien, T

    1990-05-01

    1. It is known that females have a lower skin perfusion than males. In women there are also differences in blood flow at different reproductive stages of their lives. As an initial investigation of the possible contribution of sex hormones to these differences, we studied skin and forearm blood flow during the natural changes in hormone levels which occur during the menstrual cycle. 2. Thirty-one healthy female volunteers were studied. The effect of a standardized finger cooling test (immersion of a gloved hand in a 16 degrees C water bath) on finger skin temperature and on laser Doppler flux in the finger, and forearm blood flow (strain gauge venous occlusion plethysmography) was assessed at four different times during one cycle: during menstruation, 1 day before ovulation, 2 days after ovulation and at the mid-luteal phase. Test days were determined by daily measurements of basal body temperature and were confirmed afterwards by determinations of serum luteinizing hormone, follicle-stimulating hormone, 17 beta-oestradiol and progesterone. 3. Peripheral skin circulation varied significantly within one menstrual cycle. The extremes were a mean finger skin temperature of 25.9 +/- 3.0 degrees C in the luteal phase compared with 28.4 +/- 3.7 degrees C in the pre-ovulatory phase (P = 0.002). The respective values for the mean laser Doppler flux were 18.4 +/- 10.9 compared with 29.2 +/- 16.4 arbitrary units (P = 0.003). 4. Baseline forearm muscle blood flow also varied significantly (P = 0.04) within one menstrual cycle, with low values in the menstrual phase compared with the other phases.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Analysis of red blood cells' dynamic status in a simulated blood circulation system using an ultrahigh-speed simultaneous framing optical electronic camera.

    PubMed

    Zhang, Qiang; Li, Zeren; Zhao, Shuming; Wen, Weifeng; Chang, Lihua; Yu, Helian; Jiang, Tianlun

    2017-02-01

    Alterations in the morphologic and mechanical properties of red blood cells (RBCs) are considered direct indicators of blood quality. Current measures of characterizing these properties in vivo are limited by the complicated hemodynamic environment. To better evaluate the quality of fresh and stored blood, a new research platform was constructed to evaluate the hemodynamic characteristics of RBCs. The research platform consists mostly of a microfluidic chip, microscope, and ultrahigh-speed simultaneous framing optical electronic camera (USFOEC). The microfluidic chip was designed to simplify the complicated hemodynamic environment. The RBCs were diluted in erythrocyte preservative fluid and infused into the microfluidic channels. After approximately 600× magnification of using the microscope and camera, the RBCs' dynamic images were captured by the USFOEC. Eight sequential and blur-free images were simultaneously captured by the USFOEC system. Results showed that RBC deformation changed with flow velocity and stored RBCs were less sensitive to deformation (Kfresh  < Kstored ). The frozen-stored RBCs were better able to sustain hydrodynamic stress (DI49day  = 0.128 vs. DIfrozen  = 0.118) than cold-stored RBCs but more sensitive to variations in flow speed (K49day  = 1626.2 vs. Kfrozen  = 1318.2). Results showed that the stored RBCs had worse deformability than fresh RBCs, but frozen-stored RBCs may incur less damage during storage than those stored at merely cold temperatures. This USFOEC imaging system can serve as a platform for direct observation of cell morphological and mechanical properties in a medium similar to a physiologic environment. © 2016 International Society for Advancement of Cytometry.

  1. 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.

  2. Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity.

    PubMed

    Hammer, C; Stepniak, B; Schneider, A; Papiol, S; Tantra, M; Begemann, M; Sirén, A-L; Pardo, L A; Sperling, S; Mohd Jofrry, S; Gurvich, A; Jensen, N; Ostmeier, K; Lühder, F; Probst, C; Martens, H; Gillis, M; Saher, G; Assogna, F; Spalletta, G; Stöcker, W; Schulz, T F; Nave, K-A; Ehrenreich, H

    2014-10-01

    In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function.

  3. Circulating thrombopoietin levels in normal healthy blood donors and in aplastic anemia patients in relation to disease severity

    PubMed Central

    Singh, Abhay; Verma, Anupam; Nityanand, Soniya; Chaudhary, Rajendra; Elhence, Priti

    2015-01-01

    Background: Thrombopoietin (TPO) is the key hematopoietic growth factor regulating the production of platelets from bone marrow megakaryocytes and maintaining platelet hemostasis. This study was done to find any relationship between the levels of thrombopoietin and the severity of disease in patients with aplastic anemia. Materials and Methods: Serum samples were collected from 52 patients with a confirmed diagnosis of aplastic anemia and 45 normal healthy blood donors of both sexes over a period of 2 years, and TPO was estimated by using commercially available TPO-specific-enzyme-linked immunosorbent assay. Results: The median TPO level of 1190 pg/ml (range 625-7651 pg/ml) in aplastic anemia patients was significantly higher than the median TPO level of 121.1 pg/ml (81.25-237.7 pg/ml) in normal healthy blood donors (P = 0.000). No significant difference was observed in TPO levels of male and female patients (P = 0.453). The median TPO concentrations observed in very severe aplastic anemia, severe aplastic anemia, and nonsevere aplastic anemia were 2765 pg/ml (range 625-6451 pg/ml), 1190 pg/ml (range 672.1-7651 pg/ml), and 1111.5 pg/ml (range 761.1-2289.2 pg/ml), respectively. TPO in patients of very severe aplastic anemia was significantly higher than patients of nonsevere aplastic anemia (P = 0.043), with no significant relation among rest of the groups. Discussion: TPO levels in aplastic anemia patients were significantly higher than in healthy blood donors; however, in aplastic anemia patients TPO levels were significantly higher only in patients with very severe disease. PMID:25722577

  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. Particle-Based Methods for Multiscale Modeling of Blood Flow in the Circulation and in Devices: Challenges and Future Directions

    PubMed Central

    Yamaguchi, Takami; Ishikawa, Takuji; Imai, Y.; Matsuki, N.; Xenos, Mikhail; Deng, Yuefan; Bluestein, Danny

    2010-01-01

    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. PMID:20336827

  6. Differential inhibitory action of apixaban on platelet and fibrin components of forming thrombi: Studies with circulating blood and in a platelet-based model of thrombin generation

    PubMed Central

    Arellano-Rodrigo, Eduardo; Reverter, Joan Carles; Lopez-Farre, Antonio; Diaz-Ricart, Maribel; Badimon, Juan Jose; Escolar, Gines

    2017-01-01

    Introduction Mechanisms of action of direct oral anticoagulants (DOAC) suggest a potential therapeutic use in the prevention of thrombotic complications in arterial territories. However, effects of DOACs on platelet activation and aggregation have not been explored in detail. We have investigated the effects of apixaban on platelet and fibrin components of thrombus formation under static and flow conditions. Methods We assessed the effects of apixaban (10, 40 and 160 ng/mL) on: 1) platelet deposition and fibrin formation onto a thrombogenic surface, with blood circulating at arterial shear-rates; 2) viscoelastic properties of forming clots, and 3) thrombin generation in a cell-model of coagulation primed by platelets. Results In studies with flowing blood, only the highest concentration of apixaban, equivalent to the therapeutic Cmax, was capable to significantly reduce thrombus formation, fibrin association and platelet-aggregate formation. Apixaban significantly prolonged thromboelastometry parameters, but did not affect clot firmness. Interestingly, results in a platelet-based model of thrombin generation under more static conditions, revealed a dose dependent persistent inhibitory action by apixaban, with concentrations 4 to 16 times below the therapeutic Cmax significantly prolonging kinetic parameters and reducing the total amount of thrombin generated. Conclusions Our studies demonstrate the critical impact of rheological conditions on the antithrombotic effects of apixaban. Studies under flow conditions combined with modified thrombin generation assays could help discriminating concentrations of apixaban that prevent excessive platelet accumulation, from those that deeply impair fibrin formation and may unnecessarily compromise hemostasis. PMID:28192448

  7. Microsatellite (GT)(n) repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions.

    PubMed

    Daidone, Viviana; Cattini, Maria Grazia; Pontara, Elena; Sartorello, Francesca; Gallinaro, Lisa; Marotti, Alberto; Scaroni, Carla; Pagnan, Antonio; Casonato, Alessandra

    2009-02-01

    Von Willebrand factor (VWF) levels vary considerably in normal individuals, influenced by inherited and acquired modulators. ABO blood group is the major inherited determinant of VWF levels, but a role has also been attributed to the VWF gene promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being associated with higher VWF levels than haplotype 2 (-3268C/-2709T/-2661G/-2527A), and the polymorphic locus (GT)(n) modulating the shear stress-induced activation of the VWF promoter. We characterized the (GT)(n) of the VWF promoter in 394 healthy individuals and assessed whether its variable length influenced VWF levels in normal conditions. (GT)(n) proved highly polymorphic, with alleles from 15 to 24 repeats long. (GT)(21) and (GT)(19) were the most common variants (37.4% and 34.4%, respectively). Short GT repeats (15-19) segregated mainly with haplotype 1, long GT repeats (20-24) with haplotype 2 (p < 0.0001). The number of GT repeats did not correlate with VWF levels, nor did such levels correlate with haplotypes 1 and 2, considered alone or in association with the (GT)(n) locus. We conclude that (GT)(n) and -3268/-2709/-2661/-2527 loci are in strong linkage disequilibrium. This polymorphic region of the VWF promoter does not affect VWF levels under normal conditions, though it might represent an environmentally activable VWF regulation site.

  8. The Comparative Effects of Sports Massage, Active Recovery, and Rest in Promoting Blood Lactate Clearance After Supramaximal Leg Exercise

    PubMed Central

    Martin, Nancy A.; Zoeller, Robert F.; Robertson, Robert J.; Lephart, Scott M.

    1998-01-01

    Objective: To determine the comparative effect of sports massage, active recovery, and rest on promoting blood lactate clearance after maximal anaerobic (supramaximal) leg exercise. Design and Setting: A counterbalanced experimental design with repeated measures was used. The repeated measures were the three treatment conditions. The order of the conditions was determined by random assignment to a counterbalanced test sequence. All data were collected in the Human Energy Research Laboratory at the University of Pittsburgh. Subjects: Ten male competitive cyclists volunteered for this investigation. Measurements: Serial venous blood samples were drawn and analyzed for blood lactate concentration for each test condition. Results: There were significant main effects for both absolute and relative values of blood lactate concentration between the three treatment groups and across time within groups. Conclusions: After supramaximal leg exercise, active recovery produced significant decreases in both absolute and relative measures of blood lactate concentration when compared with the sports massage and rest conditions. No significant difference was found between sports massage and rest for either absolute or relative changes in blood lactate concentration. PMID:16558481

  9. Methylation of the BRCA1 promoter in peripheral blood DNA is associated with triple-negative and medullary breast cancer.

    PubMed

    Gupta, Satish; Jaworska-Bieniek, Katarzyna; Narod, Steven A; Lubinski, Jan; Wojdacz, Tomasz K; Jakubowska, Anna

    2014-12-01

    It has been proposed that methylation signatures in blood-derived DNA may correlate with cancer risk. In this study, we evaluated whether methylation of the promoter region of the BRCA1 gene detectable in DNA from peripheral blood cells is a risk factor for breast cancer, in particular for tumors with pathologic features characteristic for cancers with BRCA1 gene mutations. We conducted a case-control study of 66 breast cancer cases and 36 unaffected controls. Cases were triple-negative or of medullary histology, or both; 30 carried a constitutional BRCA1 mutation and 36 did not carry a mutation. Blood for DNA methylation analysis was taken within three months of diagnosis. Methylation of the promoter of the BRCA1 gene was measured in cases and controls using methylation-sensitive high-resolution melting (MS-HRM). A sample with any detectable level of methylation was considered to be positive. Methylation of the BRCA1 promoter was detected in 15 of 66 cases and in 2 of 36 controls (OR 5.0, p = 0.03). Methylation was present in 15 of 36 women with breast cancer and without germline BRCA1 mutation, but in none of 30 women with breast cancer and a germline mutation (p < 0.01). The association between methylation and breast cancer was restricted to women with no constitutional BRCA1 mutation (OR 12.1, p = 0.0006). Methylation of the promoter of the BRCA1 gene detectable in peripheral blood DNA may be a marker of increased susceptibility to triple-negative or medullary breast cancer.

  10. Comparing Peripheral Blood Mononuclear Cell DNA and Circulating Plasma viral RNA pol Genotypes of Subtype C HIV-1.

    PubMed

    Banks, Lauren; Gholamin, Sharareh; White, Elizabeth; Zijenah, Lynn; Katzenstein, David A

    2012-02-01

    INTRODUCTION: Drug resistance mutations (DRM) in viral RNA are important in defining to provide effective antiretroviral therapy (ART) in HIV-1 infected patients. Detection of DRM in peripheral blood mononuclear cell (PBMC) DNA is another source of information, although the clinical significance of DRMs in proviral DNA is less clear. MATERIALS AND METHODS: From 25 patients receiving ART at a center in Zimbabwe, 32 blood samples were collected. Dideoxy-sequencing of gag-pol identified subtype and resistance mutations from plasma viral RNA and proviral DNA. Drug resistance was estimated using the calibrated population resistance tool on www.hivdb.stanford.edu database. Numerical resistance scores were calculated for all antiretroviral drugs and for the subjects' reported regimen. Phylogenetic analysis as maximum likelihood was performed to determine the evolutionary distance between sequences. RESULTS: Of the 25 patients, 4 patients (2 of which had given 2 blood samples) were not known to be on ART (NA) and had exclusively wild-type virus, 17 had received Protease inhibitors (PI), 18, non-nucleoside reverse transcriptase inhibitors (NNRTI) and 19, two or more nucleoside reverse transcriptase inhibitors (NRTI). Of the 17 with history of PI, 10 had PI mutations, 5 had minor differences between mutations in RNA and DNA. Eighteen samples had NNRTI mutations, six of which demonstrated some discordance between DNA and RNA mutations. Although NRTI resistance mutations were frequently different between analyses, mutations resulted in very similar estimated phenotypes as measured by resistance scores. The numerical resistance scores from RNA and DNA for PIs differed between 2/10, for NNRTIs between 8/18, and for NRTIs between 17/32 pairs. When calculated resistance scores were collapsed, 3 pairs showed discordance between RNA and DNA for at least one PI, 6 were discordant for at least one NNRTI and 11 for at least one NRTI. Regarding phylogenetic evolutionary analysis, all

  11. 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

  12. Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure.

    PubMed

    Ahmari, Niousha; Schmidt, Jordan T; Krane, Gregory A; Malphurs, Wendi; Cunningham, Bruce E; Owen, Jennifer L; Martyniuk, Christopher J; Zubcevic, Jasenka

    2016-07-01

    Hypertension (HTN) is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the molecular and neural mechanisms underlying this interaction have not been characterized. Here, we transplanted whole BM cells from the beta 1 and 2 adrenergic receptor (AdrB1(tm1Bkk)AdrB2(tm1Bkk)/J) knockout (KO) mice into near lethally irradiated C57BL/6J mice to generate a BM AdrB1.B2 KO chimera. This allowed us to evaluate the role of the BM beta 1 and beta 2 adrenergic receptors in mediating BM IS homeostasis and regulating blood pressure (BP) in an otherwise intact physiological setting. Fluorescence-activated cell sorting demonstrated that a decrease in systolic and mean BP in the AdrB1.B2 KO chimera is associated with a decrease in circulating inflammatory T cells, macrophage/monocytes, and neutrophils. Transcriptomics in the BM identified 7,419 differentially expressed transcripts between the C57 and AdrB1.B2 KO chimera. Pathway analysis revealed differentially expressed transcripts related to several cell processes in the BM of C57 compared with AdrB1.B2 KO chimera, including processes related to immunity (e.g., T-cell activation, T-cell recruitment, cytokine production, leukocyte migration and function), the cardiovascular system (e.g., blood vessel development, peripheral nerve blood flow), and the brain (e.g., central nervous system development, neurite development) among others. This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP.

  13. [Influence of mydocalm on the degree of intra-abdominal hypertension and local blood circulation in the intestinal wall in experiment].

    PubMed

    Sapegin, V I; Sapegin, I D; Il'chenko, F N

    2014-01-01

    The effect of mydocalm (tolperison, 5 mg/kg single dose) on the dynamics of intra-abdominal hypertension (IAH), blood circulation regulation, and oxygen balance in the tissues of intestinal wall were studied in acute experiments on rabbits. Using a special stand of original design, the initial IAH level was modeled at 200 mm H2O with the subsequent stopping of further receipt of liquid during 3 hours in an elastic container in the abdominal cavity. During 3-h observation without drug administration, no changes in IAH due to the tone of muscles of the frontal abdominal wall takes place, but there is progressive deceleration of local blood flow (-35.33 + 0.99%, p < 0.01), suppressed dilation (-20.02 + 0.54%, p < 0.01) and constriction (-60.45 + 1.17%, p < 0.01) reactivity of vessels, and decreased oxygen tension (-47.18 + 0.75%, p < 0.01) in the intestinal wall at the end of experiment. The introduction of mydocalm reduces the tone of muscles of the frontal abdominal wall, which leads to a decrease in IAH (maximum effect after 1.5 hours, -20.81 + 0.84%, p < 0.01) and prevents decrease in the local blood flow (-26.77 + 0.41%, p < 0.01), suppression of dilation (-16.51 + 0.34%, p < 0.01) and constriction (-37.85 + 0.61%, p < 0.01) reactivity of vessels, and reduction in oxygen tension (-36.60 + 1.18%, p < 0.01) at the end of experiment. The administration of mydocalm can extend the limits of application of a conservative therapy for patients with IAH and to improve the results.

  14. Obstetricians and their role in cord blood banking: promoting a public model.

    PubMed

    Herlihy, Mary M; Delpapa, Ellen H

    2013-04-01

    Umbilical cord blood, the blood remaining in the umbilical cord at birth, can be collected at birth and be a source of stem cells for a patient in need of a bone marrow transplant. Obstetricians and other health care practitioners are recognized as a patient's primary source for medical information affecting the mother and her neonate and frequently are asked to provide education and guidance regarding options of private and public cord blood banking. As the use of cord blood continues to grow in medicine and research uncovers more potential for cord blood, cord blood banking has become an important resource. The Stem Cell Therapeutic and Research Act has provided funding to expand public banking initiatives in the United States and to create a more ethnically diverse inventory of units. Private storage is not advocated unless there is an identified need in the family such that banked cord blood would offer a benefit. A recent report outlined the challenges of increasing participation and inventory, particularly among minority groups. Obstetricians and other health care practitioners should have a primary role in efforts to increase awareness of umbilical cord blood donation and be involved in initiatives to expand current public banking activities.

  15. 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.

  16. Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent.

    PubMed

    Starosolski, Zbigniew; Villamizar, Carlos A; Rendon, David; Paldino, Michael J; Milewicz, Dianna M; Ghaghada, Ketan B; Annapragada, Ananth V

    2015-05-18

    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.

  17. 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

  18. Polyethylene glycol (PEG) modified 99mTc-HMPAO-liposome for improving blood circulation and biodistribution: the effect of the extent of PEGylation.

    PubMed

    Lee, Chang-Moon; Choi, Yongdoo; Huh, Eun Jeong; Lee, Ki Young; Song, Ho-Chun; Sun, Min Jung; Jeong, Hwan-Jeong; Cho, Chong-Su; Bom, Hee-Seung

    2005-12-01

    Modification of liposomes using polyethylene glycol (PEG) results in steric hindrance to the phagocyte system and prolongation of blood circulation time. However, PEGylation can reduce radiolabeling efficiency (RE) when using the glutathione method for radiolabeling the liposomes. Therefore, we investigated the effect of the extent of PEGylation (PEG extent (PEGExt): 0, 5, 9.6, and 13.7 mol%) on the in vivo biodistribution of liposomes in Wistar rats, and RE with technetium-(99m) ((99m)Tc). PEGylated liposomes were prepared with egg phosphatidylcholine (egg PC, 1.85 mol%), cholesterol (1.0 mol%), and distearoylphosphatidylethanolamine-N-[polyethylene glycol] (DSPE-PEG; 0, 5, 9.6, and 13.7 mol%, respectively). The size distribution of the PEGylated liposomes was analyzed by a dynamic light scattering. The (99m)Tc-hexamethylpropylene-amine oxime ((99m)Tc-HMPAO) complexes were used for radiolabeling of preformed liposomes. The labeling efficiency and stability was analyzed with Sephadex G-15 column, and the biodistribution studies of (99m)Tc-liposomes after intravenous (i.v.) injection were also investigated with Wistar rats. The sizes of PEGylated liposomes decreased by increasing the PEGExt to 9.6 mol%, whereas sizes increased at 13.7 mol%. RE of (99m)Tc were greater than 90% for all PEGExt tested, and radiolabeling stability in human plasma was enhanced as a function of PEGExt. Liposomes without PEG were cleared rapidly from the blood and accumulated preferentially in the liver and the spleen. When PEGExt was increased, the accumulation in the organs decreased. This accumulation of PEG was maximized at 9.6 mol%. Accumulation of the liposomes in the spleen was increased again when PEGExt increased to 13.7 mol%. The splenic uptake of liposomes seemed to be dependent not only on PEGExt but also on the size of the liposomes. In conclusion, the PEG chains on the surface of liposome have no influence on the labeling efficiency, and the prolongation of circulation time

  19. Two putative protein export regulators promote Plasmodium blood stage development in vivo.

    PubMed

    Matz, Joachim M; Matuschewski, Kai; Kooij, Taco W A

    2013-09-01

    Protein export is considered an essential feature of malaria parasite blood stage development. Here, we examined five components of the candidate Plasmodium translocon of exported proteins (PTEX), a complex thought to mediate protein export across the parasitophorous vacuole membrane into the host cell. Using the murine malaria model parasite Plasmodium berghei, we succeeded in generating parasite lines lacking PTEX88 and thioredoxin 2 (TRX2). Repeated attempts to delete the remaining three translocon components failed, suggesting essential functions for EXP2, PTEX150, and heat shock protein 101 (HSP101) during blood stage development. To analyze blood infections of the null-mutants, we established a flow cytometry-assisted intravital competition assay using three novel high fluorescent lines (Bergreen, Beryellow, and Berred). Although blood stage development of parasites lacking TRX2 was affected, the deficit was much more striking in PTEX88 null-mutants. The multiplication rate of PTEX88-deficient parasites was strongly reduced resulting in out-competition by wild-type parasites. Endogenous tagging revealed that TRX2::tag resides in distinct punctate organelles of unknown identity. PTEX88::tag shows a diffuse intraparasitic pattern in blood stage parasites. In trophozoites, PTEX88::tag also localized to previously unrecognized extensions reaching from the parasite surface into the erythrocyte cytoplasm. Together, our results indicate auxiliary roles for TRX2 and PTEX88 and central roles for EXP2, PTEX150, and HSP101 during P. berghei blood infection.

  20. 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

  1. Regulation of inflammatory chemokine receptors on blood T cells associated to the circulating versus liver chemokines in dengue fever.

    PubMed

    de-Oliveira-Pinto, Luzia Maria; Marinho, Cíntia Ferreira; Povoa, Tiago Fajardo; de Azeredo, Elzinandes Leal; de Souza, Luiza Assed; Barbosa, Luiza Damian Ribeiro; Motta-Castro, Ana Rita C; Alves, Ada M B; Ávila, Carlos André Lins; de Souza, Luiz José; da Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Paes, Marciano Viana; Kubelka, Claire Fernandes

    2012-01-01

    Little is known about the role of chemokines/chemokines receptors on T cells in natural DENV infection. Patients from DENV-2 and -3- outbreaks were studied prospectively during the acute or convalescent phases. Expression of chemokine receptor and activation markers on lymphocyte subpopulations were determined by flow cytometry analysis, plasma chemokine ligands concentrations were measured by ELISA and quantification of CCL5/RANTES(+) cells in liver tissues from fatal dengue cases was performed by immunochemistry. In the acute DENV-infection, T-helper/T-cytotoxic type-1 cell (Th1/Tc1)-related CCR5 is significantly higher expressed on both CD4 and CD8 T cells. The Th1-related CXCR3 is up-regulated among CD4 T cells and Tc2-related CCR4 is up-regulated among CD8 T cells. In the convalescent phase, all chemokine receptor or chemokine ligand expression tends to reestablish control healthy levels. Increased CCL2/MCP-1 and CCL4/MIP-1β but decreased CCL5/RANTES levels were observed in DENV-patients during acute infection. Moreover, we showed an increased CD107a expression on CCR5 or CXCR3-expressing T cells and higher expression of CD29, CD44(HIGH) and CD127(LOW) markers on CCR4-expressing CD8 T cells in DENV-patients when compared to controls. Finally, liver from dengue fatal patients showed increased number of cells expressing CCL5/RANTES in three out of four cases compared to three death from a non-dengue patient. In conclusion, both Th1-related CCR5 and CXCR3 among CD4 T cells have a potential ability to exert cytotoxicity function. Moreover, Tc1-related CCR5 and Tc2-related CCR4 among CD8 T cells have a potential ability to exert effector function and migration based on cell markers evaluated. The CCR5 expression would be promoting an enhanced T cell recruitment into liver, a hypothesis that is corroborated by the CCL5/RANTES increase detected in hepatic tissue from dengue fatal cases. The balance between protective and pathogenic immune response mediated by

  2. High-performance size-based microdevice for the detection of circulating tumor cells from peripheral blood in rectal cancer patients.

    PubMed

    Sun, Wenjie; Jia, Chunping; Huang, Ting; Sheng, Weiqi; Li, Guichao; Zhang, Honglian; Jing, Fengxiang; Jin, Qinghui; Zhao, Jianlong; Li, Gang; Zhang, Zhen

    2013-01-01

    Since individualized therapy becomes more and more important in the treatment of rectal cancer, an accurate and effective approach should be established in the clinical settings to help physicians to make their decisions. Circulating tumor cells (CTCs), originated from either primary or metastatic cancer, could provide important information for diagnosis and monitoring of cancer. However, the implication and development of CTCs are limited due to the extreme rarity of these tumor cells. In this study we fabricated a simple and high-performance microfluidic device, which exploited numerous filtered microchannels in it to enrich the large-sized target tumor cells from whole blood. A very high CTC capture efficiency (average recovery rate: 94%) was obtained in this device at the optimum flow rate of 0.5 mL/h and channel height of 5 µm. Additionally, we used this device for detecting CTCs in 60 patients with rectal cancer. The CTC counts of rectal cancer patients were significantly higher than those in healthy subjects. Furthermore, the CTC counts detected by this device were significantly higher than those by EpCAM bead-based method for rectal cancer patients with various stage. Especially, for localized rectal cancer patients, the positive rates of samples with more than 3 CTCs per 5 mL blood by use of microdevice vs. EpCAM-based ones were 100% vs. 47%, respectively. Thus, this device provides a new and effective tool for accurate identification and measurement of CTCs in patients with rectal cancer, and has broad potential in clinical practice.

  3. Disseminated tumor cells in bone marrow and circulating tumor cells in blood of breast cancer patients: current state of detection and characterization.

    PubMed

    Riethdorf, Sabine; Pantel, Klaus

    2008-01-01

    Despite the progress resulting from early detection and improved adjuvant therapy, the prognosis of breast cancer patients is still limited by the occurrence of distant metastases largely due to clinically occult micrometastases that remain undetected at primary diagnosis even by high-resolution imaging approaches. Recent research efforts have concentrated on the identification of additional parameters allowing individual risk assessment and stratification of patients for targeted therapies, since traditional prognostic factors are not sufficient to predict metastatic relapse and treatment decisions are still mainly based on statistical risk parameters. Highly sensitive and specific immunocytochemical and molecular assays now enable the detection and characterization of disseminated and circulating tumor cells (DTCs and CTCs, respectively) at the single cell level in bone marrow (BM) and peripheral blood, providing insights into the first crucial steps of the metastatic cascade. However, because of the still high variability of results in DTC/CTC detection, the necessity of standardized approaches will be discussed. A large number of studies showed that the presence of DTCs in BM has prognostic impact for primary breast cancer patients. DTCs are likely to escape from chemotherapy by maintaining a dormant nonproliferating state. There is also evidence for a stem cell-like phenotype of DTCs, probably contributing to the opportunity to escape from dormancy control and to start expansion to manifest metastases. Blood would also be an ideal source for the detection and monitoring of CTCs because of an easy noninvasive sampling procedure enabling repeated analyses. While prognostic significance of CTCs could be reliably demonstrated for metastatic breast cancer, studies to analyze the impact of CTCs in primary breast cancer patients and the potential to replace or supplement BM analysis are still ongoing. Furthermore, molecular characterization of CTCs might contribute

  4. 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.

  5. 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.

  6. Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation - description of a novel in vitro model.

    PubMed

    Ehnert, Sabrina; Freude, Thomas; Ihle, Christoph; Mayer, Larissa; Braun, Bianca; Graeser, Jessica; Flesch, Ingo; Stöckle, Ulrich; Nussler, Andreas K; Pscherer, Stefan

    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.

  7. eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood.

    PubMed

    Zou, Jinfeng; Wang, Edwin

    2017-04-04

    With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86-0.96) and high recall rates (0.79-0.92) for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78-0.92) and recall rates (0.58-0.95) have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs.

  8. Dermal γδ T Cells Do Not Freely Re-Circulate Out of Skin and Produce IL-17 to Promote Neutrophil Infiltration during Primary Contact Hypersensitivity

    PubMed Central

    Jiang, Xiaodong; Park, Chang Ook; Geddes Sweeney, Jenna; Yoo, Min Jae; Gaide, Olivier; Kupper, Thomas Seth

    2017-01-01

    The role of mouse dermal γδ T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic γδ T cell receptor (TCR) and reside in murine epidermis from birth. We asked if dermal γδ cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (TRM) in mice. We found that, unlike epidermal γδ T cells (DETC), dermal γδ cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22. We created GFP+: GFP− parabiotic mice and found that dermal γδ T cells re-circulate very slowly—more rapidly than authentic αβ TCR TRM, but more slowly than the recently described dermal αβ TCR T migratory memory cells (TMM). Mice lacking the TCR δ gene (δ-/-) had a significant reduction of 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS). We created mice deficient in dermal γδ T cells but not DETC, and these mice also showed a markedly reduced CHS response after DNFB challenge. The infiltration of effector T cells during CHS was not reduced in dermal γδ T cell-deficient mice; however, infiltration of Gr-1+CD11b+ neutrophils, as well as ear swelling, was reduced significantly. We next depleted Gr-1+ neutrophils in vivo, and demonstrated that neutrophils are required for ear swelling, the accepted metric for a CHS response. Depletion of IL-17-producing dermal Vγ4+ cells and neutralization of IL-17 in vivo, respectively, also led to a significantly reduced CHS response and diminished neutrophil infiltration. Our findings here suggest that dermal γδ T cells have an intermediate phenotype of T cell residence, and play an important role in primary CHS through producing IL-17 to promote neutrophil infiltration. PMID:28081153

  9. The Effects of Conditions of Cerebral Anoxia, on Phospholipids, Metabolism, and Circulation of the Brain.

    DTIC Science & Technology

    Anoxia, *Phospholipids, Blood circulation, Pathology, Blood plasma , Erythrocytes, Patients, Metabolism, Blood chemistry, Brain, Experimental data, Dogs, Laboratory animals, Tables(Data), Blood diseases

  10. Blood

    MedlinePlus

    ... increased red blood cell destruction can affect teens: G6PD deficiency. G6PD is an enzyme that helps to protect ... can cause red cells to hemolyze, or burst. G6PD deficiency is a common hereditary disease among people of ...

  11. Bletilla striata Micron Particles Function as a Hemostatic Agent by Promoting Rapid Blood Aggregation

    PubMed Central

    Zhang, Chen; Zeng, Rui; Liao, Zhencheng; Fu, Chaomei; Luo, Hui

    2017-01-01

    The human body cannot control blood loss without treatment. Available hemostatic agents are ineffective at treating cases of severe bleeding and are expensive or raise safety concerns. Bletilla striata serve as an inexpensive, natural, and promising alternative. However, no detailed studies on its hemostatic approach have been performed. The aim of this study was to examine the hemostatic effects of B. striata Micron Particles (BSMPs) and their hemostatic mechanisms. We prepared and characterized BSMPs of different size ranges and investigated their use as hemostatic agent. BSMPs of different size ranges were characterized by scanning electron microscope. In vitro coagulation studies revealed BSMP-blood aggregate formation via stereoscope and texture analyzers. In vivo studies based on rat injury model illustrated the BSMP capabilities under conditions of hemostasis. Compared to other BSMPs of different size ranges, BSMPs of 350–250 μm are most efficient in hemostasis. As powder sizes decrease, the degree of aggregation between particles and hemostatic BSMP effects declines. The BSMP in contact with a bleeding surface locally forms a visible particle/blood aggregate as a physical barrier that facilitates hemostasis. Considering the facile preparation, low cost, and long shelf life of B. striata, BSMPs offer great potential as mechanisms of trauma treatment. PMID:28386291

  12. Extravascular red blood cells and hemoglobin promote tumor growth and therapeutic resistance as endogenous danger signals.

    PubMed

    Yin, Tao; He, Sisi; Liu, Xiaoling; Jiang, Wei; Ye, Tinghong; Lin, Ziqiang; Sang, Yaxiong; Su, Chao; Wan, Yang; Shen, Guobo; Ma, Xuelei; Yu, Min; Guo, Fuchun; Liu, Yanyang; Li, Ling; Hu, Qiancheng; Wang, Yongsheng; Wei, Yuquan

    2015-01-01

    Hemorrhage is a common clinical manifestation in patients with cancer. Intratumor hemorrhage has been demonstrated to be a poor prognostic factor for cancer patients. In this study, we investigated the role of RBCs and hemoglobin (Hb) in the process of tumor progression and therapeutical response. RBCs and Hb potently promoted tumor cell proliferation and syngenic tumor growth. RBCs and Hb activated the reactive oxygen species-NF-κB pathway in both tumor cells and macrophages. RBCs and Hb also induced chemoresistance mediated, in part, by upregulating ABCB1 gene expression. Tumor growth induced by RBCs was accompanied by an inflammatory signature, increased tumor vasculature, and influx of M2 macrophages. In both the peritoneal cavity and tumor microenvironment, extravascular RBCs rapidly recruited monocyte-macrophages into the lesion sites. In addition, RBCs and Hb increased several nucleotide-binding oligomerization domain-like receptors' expression and induced IL-1β release. Our results provide novel insights into the protumor function of RBCs and Hb as endogenous danger signals, which can promote tumor cell proliferation, macrophage recruitment, and polarization. Hemorrhage may represent a useful prognostic factor for cancer patients because of its role in tumor promotion and chemoresistance.

  13. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    PubMed Central

    Rodrigues, L.P.; Iglesias, D.; Nicola, F.C.; Steffens, D.; Valentim, L.; Witczak, A.; Zanatta, G.; Achaval, M.; Pranke, P.; Netto, C.A.

    2011-01-01

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 106 cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 106 cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation. PMID:22183246

  14. Tracking Viable Circulating Tumor Cells (CTCs) in the Peripheral Blood of Non-Small Cell Lung Cancer Patients Undergoing Definitive Radiation Therapy: Pilot Study Results

    PubMed Central

    Dorsey, Jay F.; Kao, Gary D.; MacArthur, Kelly M.; Ju, Melody; Steinmetz, David; Wileyto, E. Paul; Simone, Charles B.; Hahn, Stephen M.

    2014-01-01

    Background Assays identifying circulating tumor cells (CTC) allow noninvasive and sequential monitoring of the status of primary or metastatic tumors, potentially yielding clinically useful information. However, the effect of radiation therapy (RT) on CTC in patients with non-small cell lung cancer (NSCLC) to our knowledge has not been previously explored. Methods We describe here results of a pilot study of 30 NSCLC patients undergoing RT, from whom peripheral blood samples were assayed for CTC via an assay that identifies live cells, via an adenoviral probe that detects the elevated telomerase activity present in almost all cancer cells but not normal cells, and with validity of the assay confirmed with secondary tumor-specific markers. Patients were assayed prior to initiation of radiation (Pre-RT), during the RT treatment course, and/or after completion of radiation (Post-RT). Results The assay successfully detected CTC in the majority of patients, including 65% of patients prior to start of RT, and in patients with both EGFR wild type and mutation-positive tumors. Median counts in patients Pre-RT were 9.1 CTC/mL (range: undetectable - 571), significantly higher than the average Post-RT count of 0.6 CTC/mL (range: undetectable - 1.8) (p < 0.001). Sequential CTC counts were available in a subset of patients and demonstrated decreases after RT, except for a patient who subsequently developed distant failure. Conclusions These pilot data suggest that CTC counts appear to reflect response to RT for patients with localized NSCLC. Based on these promising results, we have launched a more comprehensive and detailed clinical trial. PMID:25241991

  15. 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

  16. Development of diabetes in non-obese diabetic mice promotes Chlamydia pneumoniae dissemination from lung to peripheral blood

    PubMed Central

    Yamaguchi, Hiroyuki; Oshio, Ichiro; Osaki, Takako; Kurata, Satoru; Yamamoto, Yoshimasa; Kamiya, Shigeru

    2006-01-01

    We examined a possible association between development of diabetes in non-obese diabetic (NOD) mice and dissemination of Chlamydia (Chlamydophila) pneumoniae from lung to peripheral blood. By real-time reverse transcription-polymerase chain reaction (RT-PCR) with primers for C. pneumoniae 16S rRNA, following multiple intranasal inoculations, we detected bacteria in lung in NOD mice with diabetes (38.5%) as well as Institute of Cancer Research, USA (ICR) mice (40%), but prevalence of bacteria in NOD mice without diabetes (pre-diabetic NOD mice and non-diabetic retired NOD mice) was very low (4.8%). The bacteria were only detected in peripheral blood mononuclear cells (PBMCs) cultured with hydrocortisone of the NOD mice with diabetes (53.8%). Results of immunostaining with fluorescein isothiocyanate-conjugated antichlamydia monoclonal antibody also showed the presence of bacterial antigens in the lungs and the PBMCs judged as positive by the RT-PCR. However, C. pneumoniae from cultured PBMCs of all NOD mice was undetected by cultivation method with inclusion-forming units assay. In addition, no influence of C. pneumoniae intranasal inoculation on development of diabetes in NOD mice was confirmed. Thus, the development of diabetes in NOD mouse appears to be one of critical factors for promoting the dissemination of C. pneumoniae from lung to peripheral blood. PMID:16623756

  17. Multiple endothelial cells constitute the tip of developing blood vessels and polarize to promote lumen formation.

    PubMed

    Pelton, John C; Wright, Catherine E; Leitges, Michael; Bautch, Victoria L

    2014-11-01

    Blood vessel polarization in the apical-basal axis is important for directed secretion of proteins and lumen formation; yet, when and how polarization occurs in the context of angiogenic sprouting is not well understood. Here, we describe a novel topology for endothelial cells at the tip of angiogenic sprouts in several mammalian vascular beds. Two cells that extend filopodia and have significant overlap in space and time were present at vessel tips, both in vitro and in vivo. The cell overlap is more extensive than predicted for tip cell switching, and it sets up a longitudinal cell-cell border that is a site of apical polarization and lumen formation, presumably via a cord-hollowing mechanism. The extent of cell overlap at the tip is reduced in mice lacking aPKCζ, and this is accompanied by reduced distal extension of both the apical border and patent lumens. Thus, at least two polarized cells occupy the distal tip of blood vessel sprouts, and topology, polarization and lumenization along the longitudinal border of these cells are influenced by aPKCζ.

  18. Multiple endothelial cells constitute the tip of developing blood vessels and polarize to promote lumen formation

    PubMed Central

    Pelton, John C.; Wright, Catherine E.; Leitges, Michael; Bautch, Victoria L.

    2014-01-01

    Blood vessel polarization in the apical-basal axis is important for directed secretion of proteins and lumen formation; yet, when and how polarization occurs in the context of angiogenic sprouting is not well understood. Here, we describe a novel topology for endothelial cells at the tip of angiogenic sprouts in several mammalian vascular beds. Two cells that extend filopodia and have significant overlap in space and time were present at vessel tips, both in vitro and in vivo. The cell overlap is more extensive than predicted for tip cell switching, and it sets up a longitudinal cell-cell border that is a site of apical polarization and lumen formation, presumably via a cord-hollowing mechanism. The extent of cell overlap at the tip is reduced in mice lacking aPKCζ, and this is accompanied by reduced distal extension of both the apical border and patent lumens. Thus, at least two polarized cells occupy the distal tip of blood vessel sprouts, and topology, polarization and lumenization along the longitudinal border of these cells are influenced by aPKCζ. PMID:25336741

  19. [Role of NO-dependent mechanisms at normal prenansy and on background of disturbance of utero placental blood circulation of white rats].

    PubMed

    Ivanova, A S; Sitnikova, O G; Nazarov, S B

    2012-01-01

    Condition of NO-dependent mechanisms, free-radical processes and calcium level in normal and on background of disturbance of uteroplacental circulation of white rats is studied. At normal pregnancy at animals activity of NO-dependent mechanisms increases, free radical processes are activated, hypocalcemia is appeared. Being injected of antagonist NO (10 mg/kg) and disturbance of uteroplacental circulation similar changes in the form of reducing of a level of nitrites, activation of free radical processes and hypercalcemia are observed. At the combined pathology synthesis of NO and nitrothyrosine increases, that in such conditions plays the protective role, providing adaptation of disturbance of uteroplacental circulation for needs of a fetus.

  20. 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.

  1. 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.

  2. Brain inositol is a novel stimulator for promoting Cryptococcus penetration of the blood-brain barrier.

    PubMed

    Liu, Tong-Bao; Kim, Jong-Chul; Wang, Yina; Toffaletti, Dena L; Eugenin, Eliseo; Perfect, John R; Kim, Kee Jun; Xue, Chaoyang

    2013-01-01

    Cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. The reason for the frequent occurrence of Cryptococcus infection in the central nervous system (CNS) is poorly understood. The facts that human and animal brains contain abundant inositol and that Cryptococcus has a sophisticated system for the acquisition of inositol from the environment suggests that host inositol utilization may contribute to the development of cryptococcal meningitis. In this study, we found that inositol plays an important role in Cryptococcus traversal across the blood-brain barrier (BBB) both in an in vitro human BBB model and in in vivo animal models. The capacity of inositol to stimulate BBB crossing was dependent upon fungal inositol transporters, indicated by a 70% reduction in transmigration efficiency in mutant strains lacking two major inositol transporters, Itr1a and Itr3c. Upregulation of genes involved in the inositol catabolic pathway was evident in a microarray analysis following inositol treatment. In addition, inositol increased the production of hyaluronic acid in Cryptococcus cells, which is a ligand known to binding host CD44 receptor for their invasion. These studies suggest an inositol-dependent Cryptococcus traversal of the BBB, and support our hypothesis that utilization of host-derived inositol by Cryptococcus contributes to CNS infection.

  3. CENTRAL NERVOUS MECHANISMS IN CIRCULATION REGULATION AND FUNCTIONAL DERANGEMENT (HYPERTENSION).

    DTIC Science & Technology

    BLOOD CIRCULATION, *CENTRAL NERVOUS SYSTEM, * HYPERTENSION , AUTONOMIC NERVOUS SYSTEM, ELECTROENCEPHALOGRAPHY, ELECTROPHYSIOLOGY, CHEMORECEPTORS...PERCEPTION, CARDIOVASCULAR SYSTEM, PATHOLOGY, REFLEXES, BEHAVIOR, BLOOD PRESSURE , ANOXIA, BRAIN, ITALY.

  4. How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Activation of circulating platelets and formation of "fibrinogen aggregates" in the presence of polycations.

    PubMed

    Watala, Cezary; Karolczak, Kamil; Kassassir, Hassan; Talar, Marcin; Przygodzki, Tomasz; Maczynska, Katarzyna; Labieniec-Watala, Magdalena

    2016-04-30

    Direct use of poly(amido)amine (PAMAM) dendrimers as drugs may be limited, due to uncertain (cyto)toxicity. Peripheral blood components, which constitute the first line of a contact with administered pharmaceuticals, may become vastly affected by PAMAM dendrimers. The aim of this study was to explore how PAMAMs' polycationicity might affect blood platelet activation and reactivity, and thus trigger various haemostatic events. We monitored blood platelet reactivity in rats with experimental diabetes upon a long-term administration of the unmodified PAMAM dendrimers. In parallel, the effects on blood flow in a systemic circulation was recorded intravitally in mice administered with PAMAM G2, G3 or G4. Compounding was the in vitro approach to monitor the impact of PAMAM dendrimers on blood platelet activation and reactivity and on selected haemostatic and protein conformation parameters. We demonstrated the activating effects of polycations on blood platelets. Some diversity of the revealed outcomes considerably depended on the used approach and the particular technique employed to monitor blood platelet function. We discovered undesirable impact of plain PAMAM dendrimers on primary haemostasis and their prothrombotic influence. We emphasize the need of a more profound verifying of all the promising findings collected for PAMAMs with the use of well-designed in vivo preclinical studies.

  5. Biomechanical forces promote blood development through prostaglandin E2 and the cAMP-PKA signaling axis.

    PubMed

    Diaz, Miguel F; Li, Nan; Lee, Hyun Jung; Adamo, Luigi; Evans, Siobahn M; Willey, Hannah E; Arora, Natasha; Torisawa, Yu-Suke; Vickers, Dwayne A; Morris, Samantha A; Naveiras, Olaia; Murthy, Shashi K; Ingber, Donald E; Daley, George Q; García-Cardeña, Guillermo; Wenzel, Pamela L

    2015-05-04

    Blood flow promotes emergence of definitive hematopoietic stem cells (HSCs) in the developing embryo, yet the signals generated by hemodynamic forces that influence hematopoietic potential remain poorly defined. Here we show that fluid shear stress endows long-term multilineage engraftment potential upon early hematopoietic tissues at embryonic day 9.5, an embryonic stage not previously described to harbor HSCs. Effects on hematopoiesis are mediated in part by a cascade downstream of wall shear stress that involves calcium efflux and stimulation of the prostaglandin E2 (PGE2)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling axis. Blockade of the PGE2-cAMP-PKA pathway in the aorta-gonad-mesonephros (AGM) abolished enhancement in hematopoietic activity. Furthermore, Ncx1 heartbeat mutants, as well as static cultures of AGM, exhibit lower levels of expression of prostaglandin synthases and reduced phosphorylation of the cAMP response element-binding protein (CREB). Similar to flow-exposed cultures, transient treatment of AGM with the synthetic analogue 16,16-dimethyl-PGE2 stimulates more robust engraftment of adult recipients and greater lymphoid reconstitution. These data provide one mechanism by which biomechanical forces induced by blood flow modulate hematopoietic potential.

  6. Bone morphogenetic protein signaling promotes morphogenesis of blood vessels, wound epidermis, and actinotrichia during fin regeneration in zebrafish.

    PubMed

    Thorimbert, Valentine; König, Désirée; Marro, Jan; Ruggiero, Florence; Jaźwińska, Anna

    2015-10-01

    Zebrafish fin regeneration involves initial formation of the wound epidermis and the blastema, followed by tissue morphogenesis. The mechanisms coordinating differentiation of distinct tissues of the regenerate are poorly understood. Here, we applied pharmacologic and transgenic approaches to address the role of bone morphogenetic protein (BMP) signaling during fin restoration. To map the BMP transcriptional activity, we analyzed the expression of the evolutionarily conserved direct phospho-Smad1 target gene, id1, and its homologs id2a and id3. This analysis revealed the BMP activity in the distal blastema, wound epidermis, osteoblasts, and blood vessels of the regenerate. Blocking the BMP function with a selective chemical inhibitor of BMP type I receptors, DMH1, suppressed id1 and id3 expression and arrested regeneration after blastema formation. We identified several previously uncharacterized functions of BMP during fin regeneration. Specifically, BMP signaling is required for remodeling of plexus into structured blood vessels in the rapidly growing regenerate. It organizes the wound epithelium by triggering wnt5b expression and promoting Collagen XIV-A deposition into the basement membrane. BMP represents the first known signaling that induces actinotrichia formation in the regenerate. Our data reveal a multifaceted role of BMP for coordinated morphogenesis of distinct tissues during regeneration of a complex vertebrate appendage.

  7. A promoter polymorphism in APJ gene is significantly associated with blood pressure changes and hypertension risk in Chinese women

    PubMed Central

    Zhao, Dalong; He, Lan; Zheng, Lihong; Xue, Jing; Wang, Bin; Pan, Hongming

    2016-01-01

    The aim of this study was to interrogate the gender-specific association of 5 well-defined polymorphisms in apelin/APJ system with both blood pressure changes and hypertension risk in a northeastern Chinese population. This is a population-based case-control study, including 650 hypertensive patients and 645 normotensive controls. Data were analyzed by STATA and Haplo.Stats. The genotype distributions of 5 study polymorphisms were in Hardy-Weinberg equilibrium in both genders. The rs7119375 and rs10501367 were completely linked. The genotypes (P = 0.001) and alleles (P < 0.001) of rs7119375 differed significantly between patients and controls in women. Carriers of rs7119375-AA genotype had significant higher systolic blood pressure (SBP) than carriers of rs7119375-GG genotype in both patients and controls of female gender (P < 0.01). Moreover, carriers of rs7119375-A allele were 1.80 times more likely to develop hypertension relative to carriers of rs7119375-GG genotype after adjusting for age, body mass index and glucose (odds ratio: 1.80; 95% confidence interval: 1.03–3.16; P = 0.040). Further allele combination analysis supported the leading contribution of rs7119375 to hypertension risk. Our findings demonstrated that the mutation of promoter polymorphism rs7119375 in APJ gene was significantly associated with elevated SBP and increased hypertension risk in Chinese women. PMID:27863393

  8. IL-21 is increased in peripheral blood of emphysema mice and promotes Th1/Tc1 cell generation in vitro.

    PubMed

    Duan, Minchao; Huang, Ying; Zhong, Xiaoning; Tang, Haijuan

    2014-06-01

    Interleukin-21 (IL-21) has been reported to be involved in many Th1-associated diseases. However, the alteration and immune regulation of IL-21 in emphysema remains unknown. In this study, we tested the levels of IFN-γ and IL-21 and the frequencies of Th1 and Tc1 in peripheral blood from cigarette smoke (CS)-exposed mice and air-exposed mice and explored the effect of IL-21 on generation of Th1 and Tc1 cells in vitro. It was found that the levels of IFN-γ and IL-21 and the frequencies of Th1, Tc1, CD4(+) IL-21(+), CD4(+) IL-21R(+), and CD8(+) IL-21R(+) T cells were much higher in CS-exposed mice. Moreover, the levels of IL-21 were correlated positively with Th1 cells and with Tc1 cells. Finally, the in vitro experiments showed that IL-21 could promote Th1/Tc1 cell generation in CS-exposed mice. These results indirectly provide evidence that IL-21 produced by CD4(+) T cells could promote Th1/Tc1 response, leading to systemic inflammation in emphysema.

  9. [Blood circulation in healthy inhabitants of the arid zone of Turkmenistan. Report 2. Use of controlled exercise test in persons with good and insufficient adaptation to high environmental temperature].

    PubMed

    Babaev, A B; Charyev, M Ch; Glezer, G A

    1984-02-01

    Bicycle ergometry was performed in 143 normal male residents of Ashkhabad in different seasons of the year. In cool weather, the direction and magnitude of hemodynamic response to exercise in Ashkhabad residents were similar to those of people from milder climatic zones. In summer, exercise-related systolic and diastolic blood pressure and the stroke index were smaller as compared to the respective values of the cool season. During the transition period (i.e. first hot summer days), blood pressure and the stroke index were the lowest, and the heart rate was somewhat increased. In hot weather, exercise produced a greater reduction in the circulating blood volume and a greater increase in the hematocrit value. Thirteen (9%) subjects with poor tolerance of hot weather were identified in the screened population. In these, hemodynamic shifts were similar to those observed in most normal subjects during inadequate acclimatization of the first hot summer days.

  10. Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.

    PubMed

    He, Jing; Tsai, Louis M; Leong, Yew Ann; Hu, Xin; Ma, Cindy S; Chevalier, Nina; Sun, Xiaolin; Vandenberg, Kirsten; Rockman, Steve; Ding, Yan; Zhu, Lei; Wei, Wei; Wang, Changqi; Karnowski, Alexander; Belz, Gabrielle T; Ghali, Joanna R; Cook, Matthew C; Riminton, D Sean; Veillette, André; Schwartzberg, Pamela L; Mackay, Fabienne; Brink, Robert; Tangye, Stuart G; Vinuesa, Carola G; Mackay, Charles R; Li, Zhanguo; Yu, Di

    2013-10-17

    Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5⁺ CD4⁺ T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5⁺ helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5⁺ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.

  11. RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

    PubMed

    Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

    2017-02-10

    The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

  12. Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice.

    PubMed

    Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel-Baki, Abdel-Azeem S; Ghanjati, Foued; Erichsen, Lars; Santourlidis, Simeon; Wunderlich, Frank; Araúzo-Bravo, Marcos J

    2017-03-18

    Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investigate the possible effects of a blood-stage vaccine on DNA methylation of gene promoters in the liver, known as effector against blood-stage malaria, using DNA methylation microarrays. Naturally susceptible Balb/c mice acquire, by protective vaccination, the potency to survive P. chabaudi malaria and, concomitantly, modifications of constitutive DNA methylation of promoters of numerous genes in the liver; specifically, promoters of 256 genes are hyper(=up)- and 345 genes are hypo(=down)-methylated (p < 0.05). Protective vaccination also leads to changes in promoter DNA methylation upon challenge with P. chabaudi at peak parasitemia on day 8 post infection (p.i.), when 571 and 1013 gene promoters are up- and down-methylated, respectively, in relation to constitutive DNA methylation (p < 0.05). Gene set enrichment analyses reveal that both vaccination and P. chabaudi infections mainly modify promoters of those genes which are most statistically enriched with functions relating to regulation of transcription. Genes with down-methylated promoters encompass those encoding CX3CL1, GP130, and GATA2, known to be involved in monocyte recruitment, IL-6 trans-signaling, and onset of erythropoiesis, respectively. Our data suggest that vaccination may epigenetically improve parts of several effector functions of the liver against blood-stage malaria, as, e.g., recruitment of monocyte/macrophage to the liver accelerated liver regeneration and extramedullary hepatic erythropoiesis, thus leading to self-healing of otherwise lethal P. chabaudi blood-stage malaria.

  13. Circulating Progenitor Cells and Scleroderma

    PubMed Central

    2010-01-01

    Scleroderma (systemic sclerosis) is a disease of unknown origins that involves tissue ischemia and fibrosis in the skin and internal organs such as the lungs. The tissue ischemia is due to a lack of functional blood vessels and an inability to form new blood vessels. Bone marrow–derived circulating endothelial progenitor cells play a key role in blood vessel repair and neovascularization. Scleroderma patients appear to have defects in the number and function of circulating endothelial progenitor cells. Scleroderma patients also develop fibrotic lesions, possibly as the result of tissue ischemia. Fibroblast-like cells called fibrocytes that differentiate from a different pool of bone marrow–derived circulating progenitor cells seem to be involved in this process. Manipulating the production, function, and differentiation of circulating progenitor cells represents an exciting new possibility for treating scleroderma. PMID:18638425

  14. The fetal circulation.

    PubMed

    Kiserud, Torvid; Acharya, Ganesh

    2004-12-30

    Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology, but with important differences. The human fetus seems to circulate less blood through the placenta, shunt less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal sheep. However, there are substantial individual variations and the pattern changes with gestational age. The normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale are functionally closely related and represent an important distributional unit for the venous return. The left portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus, the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies: increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow.

  15. 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.

  16. [Discussion on "removing stasis and regulating qi and blood" in the scraping therapy].

    PubMed

    Wu, Song; Liang, Zhong

    2016-04-01

    Stasis is the critical causative factor and pathological production considered in clinic treatment. Promoting the circulation in blood vessel and removing stasis are equally important in treatment. Stasis is interactive with qi and blood. Removing stasis aims to regulating the circulation of qi and blood. Scraping therapy is one of the major approaches to stasis removal in TCM. In clinical practice, the stasis can be removed with scraping, bleeding and cupping, etc. Additionally, removing stasis with scraping should be combined with regulating qi and blood to enhance the therapeutic effect.

  17. [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.

  18. The lens circulation.

    PubMed

    Mathias, Richard T; Kistler, Joerg; Donaldson, Paul

    2007-03-01

    The lens is the largest organ in the body that lacks a vasculature. The reason is simple: blood vessels scatter and absorb light while the physiological role of the lens is to be transparent so it can assist the cornea in focusing light on the retina. We hypothesize this lack of blood supply has led the lens to evolve an internal circulation of ions that is coupled to fluid movement, thus creating an internal micro-circulatory system, which makes up for the lack of vasculature. This review covers the membrane transport systems that are believed to generate and direct this internal circulatory system.

  19. A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis

    PubMed Central

    Abraham, Sabu; Scarcia, Margherita; Bagshaw, Richard D.; McMahon, Kathryn; Grant, Gary; Harvey, Tracey; Yeo, Maggie; Esteves, Filomena O.G.; Thygesen, Helene H.; Jones, Pamela F.; Speirs, Valerie; Hanby, Andrew M.; Selby, Peter J.; Lorger, Mihaela; Dear, T. Neil; Pawson, Tony; Marshall, Christopher J.; Mavria, Georgia

    2015-01-01

    During angiogenesis, Rho-GTPases influence endothelial cell migration and cell–cell adhesion; however it is not known whether they control formation of vessel lumens, which are essential for blood flow. Here, using an organotypic system that recapitulates distinct stages of VEGF-dependent angiogenesis, we show that lumen formation requires early cytoskeletal remodelling and lateral cell–cell contacts, mediated through the RAC1 guanine nucleotide exchange factor (GEF) DOCK4 (dedicator of cytokinesis 4). DOCK4 signalling is necessary for lateral filopodial protrusions and tubule remodelling prior to lumen formation, whereas proximal, tip filopodia persist in the absence of DOCK4. VEGF-dependent Rac activation via DOCK4 is necessary for CDC42 activation to signal filopodia formation and depends on the activation of RHOG through the RHOG GEF, SGEF. VEGF promotes interaction of DOCK4 with the CDC42 GEF DOCK9. These studies identify a novel Rho-family GTPase activation cascade for the formation of endothelial cell filopodial protrusions necessary for tubule remodelling, thereby influencing subsequent stages of lumen morphogenesis. PMID:26129894

  20. A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis.

    PubMed

    Abraham, Sabu; Scarcia, Margherita; Bagshaw, Richard D; McMahon, Kathryn; Grant, Gary; Harvey, Tracey; Yeo, Maggie; Esteves, Filomena O G; Thygesen, Helene H; Jones, Pamela F; Speirs, Valerie; Hanby, Andrew M; Selby, Peter J; Lorger, Mihaela; Dear, T Neil; Pawson, Tony; Marshall, Christopher J; Mavria, Georgia

    2015-07-01

    During angiogenesis, Rho-GTPases influence endothelial cell migration and cell-cell adhesion; however it is not known whether they control formation of vessel lumens, which are essential for blood flow. Here, using an organotypic system that recapitulates distinct stages of VEGF-dependent angiogenesis, we show that lumen formation requires early cytoskeletal remodelling and lateral cell-cell contacts, mediated through the RAC1 guanine nucleotide exchange factor (GEF) DOCK4 (dedicator of cytokinesis 4). DOCK4 signalling is necessary for lateral filopodial protrusions and tubule remodelling prior to lumen formation, whereas proximal, tip filopodia persist in the absence of DOCK4. VEGF-dependent Rac activation via DOCK4 is necessary for CDC42 activation to signal filopodia formation and depends on the activation of RHOG through the RHOG GEF, SGEF. VEGF promotes interaction of DOCK4 with the CDC42 GEF DOCK9. These studies identify a novel Rho-family GTPase activation cascade for the formation of endothelial cell filopodial protrusions necessary for tubule remodelling, thereby influencing subsequent stages of lumen morphogenesis.

  1. DUSP1 promoter methylation in peripheral blood leukocyte is associated with triple-negative breast cancer risk.

    PubMed

    Li, Jing; Chen, Yanbo; Yu, Hongyuan; Tian, Jingshen; Yuan, Fengshun; Fan, Jialong; Liu, Yupeng; Zhu, Lin; Wang, Fan; Zhao, Yashuang; Pang, Da

    2017-02-21

    DNA methylation is one of the most common epigenetic alterations, providing important information regarding cancer risk and prognosis. A case-control study (423 breast cancer cases, 509 controls) and a case-only study (326 cases) were conducted to evaluate the association of DUSP1 promoter methylation with breast cancer risk and clinicopathological characteristics. No significant association between DUSP1 methylation in peripheral blood leukocyte (PBL) DNA and breast cancer risk was observed. DUSP1 methylation was significantly associated with ER/PR-negative status; in particular, triple-negative breast cancer patients showed the highest frequency of DUSP1 methylation in both tumour DNA and PBL DNA. Soybean intake was significantly correlated with methylated DUSP1 only in ER-negative (OR 2.978; 95% CI 1.245-7.124) and PR negative (OR 2.735; 95% CI 1.315-5.692) patients. Irregular menstruation was significantly associated with methylated DUSP1 only in ER-positive (OR 3.564; 95% CI 1.691-7.511) and PR-positive (OR 3.902, 95% CI 1.656-9.194) patients. Thus, DUSP1 methylation is a cancer-associated hypermethylation event that is closely linked with triple-negative status. Further investigations are warranted to confirm the association of environmental factors, including fruit and soybean intake, irregular menstruation, and ER/PR status, with DUSP1 methylation in breast tumour DNA.

  2. Fractionated Concurrent Exercise throughout the Day Does Not Promote Acute Blood Pressure Benefits in Hypertensive Middle-aged Women

    PubMed Central

    Azevêdo, Luan M.; de Souza, Alice C.; Santos, Laiza Ellen S.; Miguel dos Santos, Rodrigo; de Fernandes, Manuella O. M.; Almeida, Jeeser A.; Pardono, Emerson

    2017-01-01

    Hypertension is a chronic disease that affects about 30% of the world’s population, and the physical exercise plays an important role on its non-pharmacological treatment. Anywise, the dose–response of physical exercise fractionation throughout the day demands more investigation, allowing new exercise prescription possibilities. Therefore, this study aimed to analyze the acute blood pressure (BP) kinetics after 1 h of exercises and the BP reactivity after different concurrent exercise (CE) sessions and its fractioning of hypertensive middle-aged women. In this way, 11 hypertensive women voluntarily underwent three experimental sessions and one control day [control session (CS)]. In the morning session (MS) and night session (NS), the exercise was fully realized in the morning and evening, respectively. For the fractionized session (FS), 50% of the volume was applied in the morning and the remaining 50% during the evening. The MS provided the greatest moments (p ≤ 0.05) of post-exercise hypotension (PEH) for systolic BP (SBP) and highest reduction of BP reactivity for SBP (~44%) and diastolic BP (DBP) (~59%) compared to CS (p ≤ 0.05). The findings of the present study have shown that MS is effective for PEH to SBP, as well as it promotes high quality of attenuation for BP reactivity, greater than the other sessions. PMID:28261583

  3. Fractionated Concurrent Exercise throughout the Day Does Not Promote Acute Blood Pressure Benefits in Hypertensive Middle-aged Women.

    PubMed

    Azevêdo, Luan M; de Souza, Alice C; Santos, Laiza Ellen S; Miguel Dos Santos, Rodrigo; de Fernandes, Manuella O M; Almeida, Jeeser A; Pardono, Emerson

    2017-01-01

    Hypertension is a chronic disease that affects about 30% of the world's population, and the physical exercise plays an important role on its non-pharmacological treatment. Anywise, the dose-response of physical exercise fractionation throughout the day demands more investigation, allowing new exercise prescription possibilities. Therefore, this study aimed to analyze the acute blood pressure (BP) kinetics after 1 h of exercises and the BP reactivity after different concurrent exercise (CE) sessions and its fractioning of hypertensive middle-aged women. In this way, 11 hypertensive women voluntarily underwent three experimental sessions and one control day [control session (CS)]. In the morning session (MS) and night session (NS), the exercise was fully realized in the morning and evening, respectively. For the fractionized session (FS), 50% of the volume was applied in the morning and the remaining 50% during the evening. The MS provided the greatest moments (p ≤ 0.05) of post-exercise hypotension (PEH) for systolic BP (SBP) and highest reduction of BP reactivity for SBP (~44%) and diastolic BP (DBP) (~59%) compared to CS (p ≤ 0.05). The findings of the present study have shown that MS is effective for PEH to SBP, as well as it promotes high quality of attenuation for BP reactivity, greater than the other sessions.

  4. DUSP1 promoter methylation in peripheral blood leukocyte is associated with triple-negative breast cancer risk

    PubMed Central

    Li, Jing; Chen, Yanbo; Yu, Hongyuan; Tian, Jingshen; Yuan, Fengshun; Fan, Jialong; Liu, Yupeng; Zhu, Lin; Wang, Fan; Zhao, Yashuang; Pang, Da

    2017-01-01

    DNA methylation is one of the most common epigenetic alterations, providing important information regarding cancer risk and prognosis. A case-control study (423 breast cancer cases, 509 controls) and a case-only study (326 cases) were conducted to evaluate the association of DUSP1 promoter methylation with breast cancer risk and clinicopathological characteristics. No significant association between DUSP1 methylation in peripheral blood leukocyte (PBL) DNA and breast cancer risk was observed. DUSP1 methylation was significantly associated with ER/PR-negative status; in particular, triple-negative breast cancer patients showed the highest frequency of DUSP1 methylation in both tumour DNA and PBL DNA. Soybean intake was significantly correlated with methylated DUSP1 only in ER-negative (OR 2.978; 95% CI 1.245–7.124) and PR negative (OR 2.735; 95% CI 1.315–5.692) patients. Irregular menstruation was significantly associated with methylated DUSP1 only in ER-positive (OR 3.564; 95% CI 1.691–7.511) and PR-positive (OR 3.902, 95% CI 1.656–9.194) patients. Thus, DUSP1 methylation is a cancer-associated hypermethylation event that is closely linked with triple-negative status. Further investigations are warranted to confirm the association of environmental factors, including fruit and soybean intake, irregular menstruation, and ER/PR status, with DUSP1 methylation in breast tumour DNA. PMID:28220843

  5. Collateral Circulation in Chronic Total Occlusions - an interventional perspective.

    PubMed

    Choo, Gim-Hooi

    2015-09-09

    Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

  6. Collateral Circulation in Chronic Total Occlusions - An Interventional Perspective

    PubMed Central

    Choo, Gim-Hooi

    2015-01-01

    Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.

  7. Ocean circulation using altimetry

    NASA Technical Reports Server (NTRS)

    Minster, Jean-Francois; Brossier, C.; Gennero, M. C.; Mazzega, P.; Remy, F.; Letraon, P. Y.; Blanc, F.

    1991-01-01

    Our group has been very actively involved in promoting satellite altimetry as a unique tool for observing ocean circulation and its variability. TOPEX/POSEIDON is particularly interesting as it is optimized for this purpose. It will probably be the first instrument really capable of observing the seasonal and interannual variability of subtropical and polar gyres and the first to eventually document the corresponding variability of their heat flux transport. The studies of these phenomena require data of the best quality, unbiased extraction of the signal, mixing of these satellite data with in situ measurements, and assimilation of the whole set into a dynamic description of ocean circulation. Our group intends to develop responses to all these requirements. We will concentrate mostly on the circulation of the South Atlantic and Indian Oceans: This will be done in close connection with other groups involved in the study of circulation of the tropical Atlantic Ocean, in the altimetry measurements (in particular, those of the tidal issue), and in the techniques of data assimilation in ocean circulation models.

  8. Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker

    PubMed Central

    Ravegnini, Gloria; Zolezzi Moraga, Juan Manuel; Maffei, Francesca; Musti, Muriel; Zenesini, Corrado; Simeon, Vittorio; Sammarini, Giulia; Festi, Davide; Hrelia, Patrizia; Angelini, Sabrina

    2015-01-01

    One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT). In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals’ FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006). In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001). Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = −0.926, p = 0.0001). With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108) in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007). While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment. PMID:26633373

  9. Relationships among Ocular Blood Flow Shown by Laser Speckle Flowgraphy, Retinal Arteriosclerotic Change, and Chorioretinal Circulation Time Obtained by Fluorescein Angiography

    PubMed Central

    Itokawa, Takashi; Hori, Yuichi

    2017-01-01

    Purpose. To determine the correlations among the mean blur rate (MBR) in the optic nerve head (ONH) shown by laser speckle flowgraphy (LSFG), retinal arteriosclerosis, and the circulation time obtained by fluorescein angiography (FA). Method. We evaluated 118 patients and assessed their time of choroidal flush, arm-to-retina time, and early and late phases of retinal circulation time (RT: sec) obtained by FA. The severity of retinal arteriosclerosis was classified according to the Scheie classification. The MBR values throughout the ONH (MBR-A), in the tissue (MBR-T), and in the vessels (MBR-V) were analyzed. Results. Patients with retinal vein occlusion (RVO) showed prolonged early and late phases of RT compared to other ocular diseases. Single and multiple regression analyses showed that the MBR-V and Scheie classification were significantly associated with both the choroidal flush and arm-to-retina times. The incidences of RVO and MVR-V were significantly associated with the early phase of RT, and the incidences of RVO, MBR-V, Scheie classification, and gender were revealed to be factors independently contributing to the late phase of RT. Conclusion. MBR-V in the ONH and retinal arteriosclerosis are important contributing factors for the circulation time of each stage obtained by FA. PMID:28331635

  10. CXCR4 pos circulating progenitor cells coexpressing monocytic and endothelial markers correlating with fibrotic clinical features are present in the peripheral blood of patients affected by systemic sclerosis.

    PubMed

    Campioni, Diana; Lo Monaco, Andrea; Lanza, Francesco; Moretti, Sabrina; Ferrari, Luisa; Fotinidi, Maria; La Corte, Renato; Cuneo, Antonio; Trotta, Francesco

    2008-08-01

    There is still controversy regarding the role of circulating endothelial and progenitor cells (CECs/CEPs) in the pathogenesis of systemic sclerosis (SSc). Using a sequential Boolean gating strategy based on a 4-color flow cytometric protocol, an increased number of CD31(pos)/CD184(pos)(CXCR4)/CD34(pos)/CD45(pos) and CD31(pos)/CD117(pos) (c-kit-R) /CD34(pos)/ CD45(pos) hematopoietic circulating progenitor cells (HCPCs) was detected in SSc patients compared with healthy subjects. In SSc, no circulating mature and progenitor endothelial cells were observed, while an enhanced generation of erythroid progenitor cells was found to be correlated with the presence of CD117+ HCPCs. The presence of freshly detected CXCR4posHCPC was correlated either to the in vitro cultured spindle-shaped endothelial like cells (SELC) with an endo/myelomonocytic profile or to SDF-1 and VEGF serum level. These data are related to more fibrotic clinical features of the disease, thus supporting a possible role of these cells in fibrosis.

  11. Dynamic Effect of Rolling Massage on Blood Flow

    NASA Astrophysics Data System (ADS)

    Chen, Yan-Yan; Yi, Hou-Hui; Li, Hua-Bing; Fang, Hai-Ping

    2009-02-01

    The Chinese traditional medical massage has been used as a natural therapy to eliminate some diseases. Here, the effect of the rolling massage frequency to the blood flow in the blood vessels under the rolling massage manipulation is studied by the lattice Boltzmann simulation. The simulation results show that when the frequency is smaller than or comparable to the pulsatile frequency of the blood flow, the effect on the blood flux by the rolling massage is small. On the contrast, if the frequency is twice or more times of the pulsatile frequency of the blood flow, the blood flux is greatly enhanced and increases linearly with respect to the frequency. Similar behavior has also been observed on the shear stress on the blood vessel walls. The result is helpful for understanding that the rolling massage has the function of promoting the blood circulation and removing the blood stasis.

  12. Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes is Not A Hallmark of Age-Related Macular Degeneration

    PubMed Central

    Oliver, Verity F; Franchina, Maria; Jaffe, Andrew E; Branham, Kari E; Othman, Mohammad; Heckenlively, John R; Swaroop, Anand; Campochiaro, Betsy; Vote, Brendan J; Craig, Jamie E; Saffery, Richard; Mackey, David A; Qian, Jiang; Zack, Donald J; Hewitt, Alex W; Merbs, Shannath L

    2014-01-01

    SUMMARY Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Aberrant DNA methylation within the promoter of IL17RC in peripheral blood mononuclear cells has recently been reported in AMD. To validate this association, we examined DNA methylation of the IL17RC promoter in peripheral blood. First, we used Illumina Human Methylation450 Bead Arrays, a widely-accepted platform for measuring global DNA methylation. Second, methylation status at multiple sites within the IL17RC promoter was determined by bisulfite pyrosequencing in two cohorts. Third, a methylation-sensitive QPCR-based assay was performed on a subset of samples. In contrast to previous findings, we did not find evidence of differential methylation between AMD cases and age-matched controls. We conclude that hypomethylation within the IL17RC gene promoter in peripheral blood is not suitable for use as a clinical biomarker of AMD. This study highlights the need for considerable replication of epigenetic association studies prior to clinical application. PMID:24373284

  13. Effects of a Taser: Conducted Energy Weapon on the Circulating Red-Blood-Cell Population and Other Factors in Sus scrofa

    DTIC Science & Technology

    2013-03-30

    currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 13-08-2013 2. REPORT TYPE Journal...15. SUBJECT TERMS TASER; Conducted energy weapon; Electronic control device; Electro-muscular disruption; Erythrocytes; red blood cells 16...Electronic control device Electro-muscular disruption Muscle contraction Erythrocytes Red blood cells Introduction Medical examiners have

  14. Inducible HGF-secreting Human Umbilical Cord Blood-derived MSCs Produced via TALEN-mediated Genome Editing Promoted Angiogenesis

    PubMed Central

    Chang, Hyun-Kyung; Kim, Pyung-Hwan; Cho, Hyun-Min; Yum, Soo-Young; Choi, Young-Jin; Son, YeonSung; Lee, DaBin; Kang, InSung; Kang, Kyung-Sun; Jang, Goo; Cho, Je-Yoel

    2016-01-01

    Mesenchymal stem cells (MSCs) promote therapeutic angiogenesis to cure serious vascular disorders. However, their survival period and cytokine-secretory capacity are limited. Although hepatocyte growth factor (HGF) can accelerate the rate of angiogenesis, recombinant HGF is limited because of its very short half-life (<3–5 minutes). Thus, continuous treatment with HGF is required to obtain an effective therapeutic response. To overcome these limitations, we produced genome-edited MSCs that secreted HGF upon drug-specific induction. The inducible HGF expression cassette was integrated into a safe harbor site in an MSC chromosome using the TALEN system, resulting in the production of TetOn-HGF/human umbilical cord blood-derived (hUCB)-MSCs. Functional assessment of the TetOn-HGF/hUCB-MSCs showed that they had enhanced mobility upon the induction of HGF expression. Moreover, long-term exposure by doxycycline (Dox)-treated TetOn-HGF/hUCB-MSCs enhanced the anti-apoptotic responses of genome-edited MSCs subjected to oxidative stress and improved the tube-formation ability. Furthermore, TetOn-HGF/hUCB-MSCs encapsulated by arginine-glycine-aspartic acid (RGD)-alginate microgel induced to express HGF improved in vivo angiogenesis in a mouse hindlimb ischemia model. This study showed that the inducible HGF-expressing hUCB-MSCs are competent to continuously express and secrete HGF in a controlled manner. Thus, the MSCs that express HGF in an inducible manner are a useful therapeutic modality for the treatment of vascular diseases requiring angiogenesis. PMID:27434585

  15. Inducible HGF-secreting Human Umbilical Cord Blood-derived MSCs Produced via TALEN-mediated Genome Editing Promoted Angiogenesis.

    PubMed

    Chang, Hyun-Kyung; Kim, Pyung-Hwan; Cho, Hyun-Min; Yum, Soo-Young; Choi, Young-Jin; Son, YeonSung; Lee, DaBin; Kang, InSung; Kang, Kyung-Sun; Jang, Goo; Cho, Je-Yoel

    2016-09-01

    Mesenchymal stem cells (MSCs) promote therapeutic angiogenesis to cure serious vascular disorders. However, their survival period and cytokine-secretory capacity are limited. Although hepatocyte growth factor (HGF) can accelerate the rate of angiogenesis, recombinant HGF is limited because of its very short half-life (<3-5 minutes). Thus, continuous treatment with HGF is required to obtain an effective therapeutic response. To overcome these limitations, we produced genome-edited MSCs that secreted HGF upon drug-specific induction. The inducible HGF expression cassette was integrated into a safe harbor site in an MSC chromosome using the TALEN system, resulting in the production of TetOn-HGF/human umbilical cord blood-derived (hUCB)-MSCs. Functional assessment of the TetOn-HGF/hUCB-MSCs showed that they had enhanced mobility upon the induction of HGF expression. Moreover, long-term exposure by doxycycline (Dox)-treated TetOn-HGF/hUCB-MSCs enhanced the anti-apoptotic responses of genome-edited MSCs subjected to oxidative stress and improved the tube-formation ability. Furthermore, TetOn-HGF/hUCB-MSCs encapsulated by arginine-glycine-aspartic acid (RGD)-alginate microgel induced to express HGF improved in vivo angiogenesis in a mouse hindlimb ischemia model. This study showed that the inducible HGF-expressing hUCB-MSCs are competent to continuously express and secrete HGF in a controlled manner. Thus, the MSCs that express HGF in an inducible manner are a useful therapeutic modality for the treatment of vascular diseases requiring angiogenesis.

  16. Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis.

    PubMed

    Bischoff, Farideh Z; Sinacori, Mina K; Dang, Dianne D; Marquez-Do, Deborah; Horne, Cassandra; Lewis, Dorothy E; Simpson, Joe Leigh

    2002-01-01

    Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.

  17. [Haemodynamic role of blood-plasma circulating cell-free DNA and contained therein high-molecular-weight CpG-rich fraction in pathogenesis of arterial hypertension and atherosclerosis obliterans of carotid arteries].

    PubMed

    Konorova, I L; Veĭko, N N; Ershova, E S; Antelava, A L; Chechetkin, A O

    2009-01-01

    The hydrodynamic resistance (HR) of blood is one of the components of the total peripheral resistance. High-molecular-weight DNA appears to decrease the HR in accordance with the Toms's effect. The present study was undertaken to investigate the HR and properties of cell-free DNA circulating in the blood plasma (hereinafter referred to as pDNA) of the control donors, patients suffering from either arterial hypertension (AH) alone or that combined with atherosclerotic lesions of the carotid arteries (CAs). Within the normal concentrations of pDNA, we revealed an inverse dependence of the HR thereupon and upon the content in pDNA of the high-molecular-weight CpG-rich fraction (CpG-DNA), i. e., a transcribed region of the ribosomal repeat (rDNA). A decrease or an increase in the pDNA concentration in all the patients examined was accompanied by an elevation of the rDNA concentration in the blood plasma. Exceeding a certain level thereof appeared to give rise to an increase in both the HR and arterial pressure (AP). Patients presenting with degree I essential AH were found to have a decreased endonuclease activity of the blood plasma, with the pDNA concentration being more than two-fold higher with no change in the rDNA content. Their HR appeared to be increased (p<0.01). Patients diagnosed as having degree II AH were characterized by a normal or decreased level of pDNA and an elevated content of pDNA, with the HR being slightly lowered. In patients presenting with atherosclerosis obliterans of the ACs, the initial manifestations of the lesions of the carotid arteries were typically revealed on the background of a lowered HR (p<0.05). All patients suffering from atherosclerotic lesions of the ACs could be subdivided into two groups, which in our opinion is probably associated with different various mechanisms of destructive damage to the arterial intima. In some of them, the pDNA concentration does not differ from the normal values, but in its composition, there is an

  18. 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

  19. 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

    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 (137)Cs. 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.

  20. [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.

  1. Vascular mineralocorticoid receptor regulates microRNA-155 to promote vasoconstriction and rising blood pressure with aging

    PubMed Central

    DuPont, Jennifer J.; McCurley, Amy; Davel, Ana P.; McCarthy, Joseph; Bender, Shawn B.; Hong, Kwangseok; Yang, Yan; Yoo, Jeung-Ki; Aronovitz, Mark; Baur, Wendy E.; Christou, Demetra D.; Hill, Michael A.; Jaffe, Iris Z.

    2016-01-01

    Hypertension is nearly universal yet poorly controlled in the elderly despite proven benefits of intensive treatment. Mice lacking mineralocorticoid receptors in smooth muscle cells (SMC-MR-KO) are protected from rising blood pressure (BP) with aging, despite normal renal function. Vasoconstriction is attenuated in aged SMC-MR-KO mice, thus they were used to explore vascular mechanisms that may contribute to hypertension with aging. MicroRNA (miR) profiling identified miR-155 as the most down-regulated miR with vascular aging in MR-intact but not SMC-MR-KO mice. The aging-associated decrease in miR-155 in mesenteric resistance vessels was associated with increased mRNA abundance of MR and of predicted miR-155 targets Cav1.2 (L-type calcium channel (LTCC) subunit) and angiotensin type-1 receptor (AgtR1). SMC-MR-KO mice lacked these aging-associated vascular gene expression changes. In HEK293 cells, MR repressed miR-155 promoter activity. In cultured SMCs, miR-155 decreased Cav1.2 and AgtR1 mRNA. Compared to MR-intact littermates, aged SMC-MR-KO mice had decreased systolic BP, myogenic tone, SMC LTCC current, mesenteric vessel calcium influx, LTCC-induced vasoconstriction and angiotensin II-induced vasoconstriction and oxidative stress. Restoration of miR-155 specifically in SMCs of aged MR-intact mice decreased Cav1.2 and AgtR1 mRNA and attenuated LTCC-mediated and angiotensin II-induced vasoconstriction and oxidative stress. Finally, in a trial of MR blockade in elderly humans, changes in serum miR-155 predicted the BP treatment response. Thus, SMC-MR regulation of miR-155, Cav1.2 and AgtR1 impacts vasoconstriction with aging. This novel mechanism identifies potential new treatment strategies and biomarkers to improve and individualize antihypertensive therapy in the elderly. PMID:27683672

  2. Does a resistance exercise session with continuous or intermittent blood flow restriction promote muscle damage and increase oxidative stress?

    PubMed

    Neto, Gabriel R; Novaes, Jefferson S; Salerno, Verônica P; Gonçalves, Michel M; Batista, Gilmário R; Cirilo-Sousa, Maria S

    2017-01-31

    The aim of this study was to compare the effect of low-load resistance exercise (LLRE) with continuous and intermittent blood flow restriction (BFR) on the creatine kinase (CK), lactate dehydrogenase (LDH), protein carbonyl (PC), thiobarbituric acid-reactive substance (TBARS) and uric acid (UA) levels in military men. The study included 10 recreationally trained men aged 19 ± 0.82 years who underwent the following experimental protocols in random order on separate days (72-96 h): 4 LLRE sessions at a 20% 1RM (one-repetition maximum [1RM]) with continuous BFR (LLRE + CBFR); 4 LLRE sessions at 20% 1RM with intermittent BFR (LLRE + IBFR) and 4 high-intensity resistance exercise (HIRE) sessions at 80% 1RM. The CK and LDH (markers of muscle damage) levels were measured before exercise (BE), 24 h post-exercise and 48 h post-exercise, and the PC, TBARS and UA (markers of oxidative stress) levels were measured BE and immediately after each exercise session. There was a significant increase in CK in the HIRE 24 post-exercise samples compared with the LLRE + CBFR and LLRE + IBFR (P = 0.035, P = 0.036, respectively), as well as between HIRE 48 post-exercise and LLRE + CBFR (P = 0.049). Additionally, there was a significant increase in CK in the LLRE + CBFR samples BE and immediately after each exercise (Δ = 21.9%) and in the HIRE samples BE and immediately after each exercise, BE and 24 post-exercise, and BE and 48 post-exercise (Δ values of 35%, 177.6%, and 177.6%, respectively). However, there were no significant changes in LDH, PC, TBARS, and UA between the protocols (P > 0.05). Therefore, a physical exercise session with continuous or intermittent BFR did not promote muscle damage; moreover, neither protocol seemed to affect the oxidative stress markers.

  3. 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.

  4. Analysis of the Survival of Arterialized Venous Toenail Flap with Reference to Changes in Blood Circulation during the Postoperative Period in 2 Patients

    PubMed Central

    Ishii, Naohiro; Shimizu, Yusuke; Aoki, Marie; Suzuki, Ayaka; Kishi, Kazuo

    2016-01-01

    Summary: Various techniques for nail reconstruction have been reported until now; however, a simple one providing good esthetic results was difficult to find. Arterialized venous toenail flap is a free flap that includes the nail bed and matrix with a pedicle formed solely by the subcutaneous vein of the toe. The use of this flap is minimally invasive and easy, and the flap has a high survival rate. The mechanism of graft survival remains unknown given the nonphysiologic circulation. To the best of our knowledge, no studies have explained this mechanism with reference to detailed postoperative course. We herein present 2 cases of nail reconstruction performed using arterialized venous toenail flap. We analyzed the postoperative course in detail, which enabled us to postulate on the mechanism of graft survival. PMID:27826474

  5. The immunologically reactive O-linked polysaccharide chains derived from circulating cathodic antigen isolated from the human blood fluke Schistosoma mansoni have Lewis x as repeating unit.

    PubMed

    Van Dam, G J; Bergwerff, A A; Thomas-Oates, J E; Rotmans, J P; Kamerling, J P; Vliegenthart, J F; Deelder, A M

    1994-10-01

    The gut-associated excretory antigen circulating cathodic antigen (CCA) was isolated by immunoaffinity chromatography from adult Schistosoma mansoni worms, which were collected from infected golden hamsters. This antigen is probably involved in protection of the schistosome gut and is increasingly used in highly sensitive and specific immunodiagnostic assays. Amino acid analysis before and after alkaline borohydride treatment of CCA and monosaccharide analysis indicated that CCA is O-glycosylated mostly via GalNAc-Thr. After reductive alkaline treatment, the O-linked carbohydrate chains were fractionated by gel-permeation chromatography, followed by normal-phase HPLC on LiChrosorb-NH2. Carbohydrate-positive fractions were investigated by one-dimensional and two-dimensional 1H-NMR spectroscopy, fast atom bombardment mass spectrometry and collision-induced-dissociation tandem mass spectrometry. The analyses showed that the low-molecular-mass O-linked oligosaccharide alditols (the minor fraction) consist of disaccharides to hexasaccharides having the Gal beta (1-3)GalNAc-OL core in common. The major carbohydrate fraction comprises a population of polysaccharides, containing Lewis x repeating units (-3)Gal beta (1-4)[Fuc alpha (1-3)]GlcNAc beta (1-). CCA-specific monoclonal antibodies and IgM antibodies in patient sera recognized the fucosylated O-linked carbohydrate antigenic structures. Since CCA evokes a strong IgM antibody response and carbohydrate structures containing repeating Lewis x units are found on circulating neutrophils, it is proposed that the antigenic poly-Lewis x polysaccharide of CCA is involved in the induction of auto-immunity against granulocytes, resulting in the mild to moderate neutropenia observed during schistosome infection.

  6. Circulating angiogenic factors associated with response and survival in patients with acute graft-versus-host disease: results from Blood and Marrow Transplant Clinical Trials Network 0302 and 0802.

    PubMed

    Holtan, Shernan G; Verneris, Michael R; Schultz, Kirk R; Newell, Laura F; Meyers, Gabrielle; He, Fiona; DeFor, Todd E; Vercellotti, Gregory M; Slungaard, Arne; MacMillan, Margaret L; Cooley, Sarah A; Blazar, Bruce R; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel J

    2015-06-01

    Circulating angiogenic factors (AF) reflect tissue healing capacity, although some AF can also contribute to inflammation and are indicative of endothelial dysfunction. The AF milieu in acute graft-versus-host disease (aGVHD) has not been broadly characterized. We hypothesized that patients with abundant AF involved in repair/regeneration versus those mediating damage/inflammation would have improved outcomes. Circulating AF known predominantly for repair/regeneration (epidermal growth factor [EGF], fibroblast growth factor-1 and -2, heparin binding-EGF-like growth factor, and vascular endothelial growth factor-A [VEGF-A], -C, and -D) and for damage/inflammation (angiopoietin-2, endothelin-1, soluble endoglin [sEng], follistatin [FS], leptin, and placental growth factor [PlGF]) were measured in a discovery set of hematopoietic cell recipients with grade III and IV aGVHD and compared with controls, then validated in 2 aGVHD cohorts enrolled in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials 0302 (n = 105, serum) and 0802 (n = 158, plasma) versus controls without aGVHD (n = 53, serum). Levels of EGF and VEGF-A were lower than in controls at the onset of aGVHD in both trials and higher with complete response to first-line aGVHD therapy in CTN 0802. FS and PlGF were elevated in aGVHD measured in either serum or plasma. At day 28 after initial aGVHD therapy, elevated FS was an independent negative prognostic factor for survival in both cohorts (hazard ratio, 9.3 in CTN 0302; 2.8 in CTN 0802). These data suggest that circulating AF are associated with clinical outcomes after aGVHD and, thus, may contribute to both pathogenesis and recovery.

  7. [Participation of the cava vein blood flow in forming the total venous return under influence of different modality stimuli on the circulation system].

    PubMed

    Samoĭlenko, A V; Iurov, A Iu

    2004-06-01

    Participation of the anterior and posterior veins cava in forming the total venous return under pressor and depressor effects, stimulation of depressing foci of the medulla's ventral part, enhancement of pulmonary ventilation, hypoxia, hypothermia, administration of acetylcholine, histamine, corinfar, was shown to depend on the blood flow shift direction in each of the veins cava, dynamics of shifts' development in time, and intensity of the stimulus. In systemic responses, the blood flow shifts in the vena cava anterior much contribute to the total venous return at the maximum of the systemic arterial pressure rise (r = 0.87) whereas contribution of the vena cava posterior is the greatest during a later occurring increase in the venous return (r = 0.84). Along with increase in the stimulus intensity the vena cava anterior's part in forming the venous return becomes more limited whereas that of the vena cava posterior is enhanced.

  8. Circulating Endothelial Cells and Procoagulant Microparticles in Patients with Glioblastoma: Prognostic Value

    PubMed Central

    Reynés, Gaspar; Vila, Virtudes; Fleitas, Tania; Reganon, Edelmiro; Font de Mora, Jaime; Jordá, María; Martínez-Sales, Vicenta

    2013-01-01

    Aim Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter. Methods Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification. Results Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001). After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99th percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004). Conclusion Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma. PMID:23922679

  9. The adaptation of the cerebral circulation to pregnancy: mechanisms and consequences

    PubMed Central

    Cipolla, Marilyn J

    2013-01-01

    The adaptation of the cerebral circulation to pregnancy is unique from other vascular beds. Most notably, the growth and vasodilatory response to high levels of circulating growth factors and cytokines that promote substantial hemodynamic changes in other vascular beds is limited in the cerebral circulation. This is accomplished through several mechanisms, including downregulation of key receptors and transcription factors, and production of circulating factors that counteract the vasodilatory effects of vascular endothelial growth factor (VEGF) and placental growth factor. Pregnancy both prevents and reverses hypertensive inward remodeling of cerebral arteries, possibly through downregulation of the angiotensin type 1 receptor. The blood–brain barrier (BBB) importantly adapts to pregnancy by preventing the passage of seizure provoking serum into the brain and limiting the permeability effects of VEGF that is more highly expressed in cerebral vasculature during pregnancy. While the adaptation of the cerebral circulation to pregnancy provides for relatively normal cerebral blood flow and BBB properties in the face of substantial cardiovascular changes and high levels of circulating factors, under pathologic conditions, these adaptations appear to promote greater brain injury, including edema formation during acute hypertension, and greater sensitivity to bacterial endotoxin. PMID:23321787

  10. Influence of matrix metalloproteinase-1 gene -1607 (1G/2G) (rs1799750) promoter polymorphism on circulating levels of MMP-1 in chronic pancreatitis.

    PubMed

    Sri Manjari, K; Nallari, Pratibha; Balakrishna, N; Vidyasagar, A; Prabhakar, B; Jyothy, A; Venkateshwari, A

    2013-08-01

    This study investigated the role of -1607 (1G/2G) (rs1799750) polymorphism of the MMP-1 gene in chronic pancreatitis. We genotyped 100 patients with chronic pancreatitis and 100 control subjects using tetra-primer ARMS-PCR followed by agarose gel electrophoresis. Serum levels of MMP-1 were determined by Elisa. Statistical analysis was applied to test the significance of the results. The genotypic and allelic distribution varied significantly between the disease group and the control subjects [OD = 1.981 (1.236-3.181), p = 0.004]. MMP-1 levels were higher in subjects homozygous for the 2G allele than in subjects with the 1G allele. The present study revealed a significant association of the MMP-1 -1607 1G/2G (rs1799750) gene promoter polymorphism with chronic pancreatitis, and it can be considered a biological marker in the etiology of chronic pancreatitis.

  11. 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.

  12. What Happens to Donated Blood?

    MedlinePlus

    ... Blood Drive Process Overview Coordinator Tools Current Programs & Promotions Recruitment Resources Running a Successful Blood Drive Multiple ... today! Enter your zip code to find: Regional Promotions Local News Blood Drives & More! Or find the ...

  13. Investigation into the promoter DNA methylation of three genes (CAMK1D, CRY2 and CALM2) in the peripheral blood of patients with type 2 diabetes.

    PubMed

    Cheng, Jia; Tang, Linlin; Hong, Qingxiao; Ye, Huadan; Xu, Xuting; Xu, Leiting; Bu, Shizhong; Wang, Qinwen; Dai, Dongjun; Jiang, Danjie; Duan, Shiwei

    2014-08-01

    Promoter DNA methylation may reflect the interaction between genetic backgrounds and environmental factors in the development of metabolic disorders, including type 2 diabetes (T2D). Calcium/calmodulin-dependent protein kinase 1D (CAMK1D), cryptochrome 2 (CRY2) and calmodulin 2 (CALM2) genes have been identified to be associated with a risk of T2D. Therefore, the aim of the present study was to investigate the contribution of promoter DNA methylation of these genes to the risk of T2D. Using bisulfite pyrosequencing technology, the DNA methylation levels of the CpG dinucleotides within the CAMK1D, CRY2 and CALM2 gene promoters were measured in 48 patients with T2D and 48 age- and gender-matched healthy controls. The results demonstrated that the promoters of these three genes were hypomethylated in the peripheral blood of all the subjects, and DNA methylation of these three genes did not contribute to the risk of T2D.

  14. Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*

    PubMed Central

    Borkowski, Abraham J.; Levin, Sam; Delcroix, Claude; Mahler, Antoinette; Verhas, Vera

    1967-01-01

    A kinetic study of the conversion of blood cholesterol into hydrocortisone was carried out in two patients through prolonged infusions of cholesterol-4-14C. The following points appear to be established by our observations: 1) The infused tracer behaved metabolically like endogenous cholesterol; it could therefore serve as a means of labeling plasma cholesterol for investigating its utilization by the adrenal cortex. 2) At rest, about 80% of hydrocortisone derived from plasma cholesterol, the other 20% thus being synthesized in situ from acetate and other unlabeled precursors. 3) Under ACTH stimulation the participation of plasma cholesterol in the synthesis of hydrocortisone was the same as at rest; the conversion of plasma cholesterol into hydrocortisone was thus proportional to the production of glucocorticosteroids by the adrenal glands. 4) The specific activities of hydrocortisone allowed us to trace its adrenal precursors including adrenal cholesterol. The kinetics of the replacement of adrenal cholesterol by plasma cholesterol underlined the functional heterogeneity of the former. The experimental data were compatible with the following model: A fraction of plasma cholesterol entering the adrenal cell is immediately available for metabolism and conversion into steroid hormones, and another fraction turns over slowly, representing some form of storage. PMID:4290583

  15. 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

  16. Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages.

    PubMed

    Bacot, Silvia M; Feldman, Gerald M; Yamada, Kenneth M; Dhawan, Subhash

    2015-02-01

    Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt-Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106-126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis.

  17. [Extracellular HMGB1 promotes the migration of cord Blood CD34⁺ cells via SDF-1/CXCR-4 axis].

    PubMed

    Yang, Lu-Lu; Sun, Zi-Min; Liu, Xin; Zhu, Xiao-Yu; Wang, Xing-Bing; Wang, Jian

    2014-10-01

    This study was aimed to investigate the effect of high mobility group box1(HMGB1) and/or stromal cell derived factor-1(SDF-1) on the migration of cord blood CD34⁺ cells, and to explore whether HMGB1 promotes cord blood CD34⁺ cell migration via SDF-1/CXCR4 axis. Cord blood mononuclear cells were isolated by Ficoll-Paque density centrifugation, CD34⁺ cells were collected by a positive immunoselection procedure (CD34 MicroBeads) according to the manufacturer's instructions, the purity of the isolated CD34⁺ cells was detected by flow cytometry. In vitro chemotaxis assays were performed using Transwell cell chambers to detect cells migration. 1 × 10⁵ cells/well cord blood CD34⁺ cells were added into the upper chambers. Different concentrations of HMGB1 and/or SDF-1 (0, 10, 25, 50, 100, 200 ng/ml) were used to detect the optimal concentrations of HMGB1 and/or SDF-1 for inducing migration of cord blood CD34⁺ cells. Freshly isolated cord blood CD34⁺ cells express CXCR4 (SDF-1 receptor), and HMGB1 receptor TLR-2,TLR-4 and RAGE. To explore which receptors were required for the synergy of HGMB1 and/or SDF-1 on cells migration, the anti-SDF-1, anti-CXCR4 and anti-RAGE antibodies were used to detect the effect of HGMB1 alone or with SDF-1 on cord blood CD34⁺ cells migration. The results showed that the purity of CD34⁺ cells isolated from cord blood mononuclear cells by magnetic cell sorting was 97.40 ± 1.26%, the 25 ng/ml SDF-1 did not induce migration of cord blood CD34⁺ cells, whereas the optimal migration was observed at 100 ng/ml. HMGB1 alone did not induce migration up to 100 ng/ml. The dose test found that the the best synergistic concentrations for cells migration were 100 ng/ml HMGB1 combined with 50 ng/ml SDF-1. The blocking test showed that both the anti-SDF-1 (4 µg/ml) and anti-CXCR4 (5 µg/ml) antibodies could block cell migration induced by HMGB1 or combined with SDF-1, but the cord blood CD34⁺ cells in the presence of anti-RAGE, anti

  18. Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients

    PubMed Central

    Harshyne, Larry A.; Nasca, Brian J.; Kenyon, Lawrence C.; Andrews, David W.; Hooper, D. Craig

    2016-01-01

    Background Glioblastoma (GBM) is an aggressive infiltrative brain tumor with a particularly poor prognosis that is characterized by microvascular proliferation, necrotic tissue, and significant infiltration of M2-like monocytes. Compromised barrier function in tumor vasculature might be expected to permit communication between the tumor microenvironment and peripheral blood. Methods To ascertain whether tumor-derived vesicles and/or factors might reach the bloodstream and what effects these molecules have on the peripheral compartment, we analyzed blood samples collected from primary GBM patients. Results Notably, a significant number of patient sera samples contained tumor exosome-reactive immunoglobulin (Ig)G2 and IgG4 antibody isotypes, which are consistent with Th2 immunity. M2-like monocytes expressing CD14+ and CD163+, another indicator of Th2 bias, are elevated in GBM patient blood and associated with high serum concentrations of colony−stimulating factor 2 and 3, as well as interleukin-2, -4, and -13, the latter 2 cytokines being hallmarks of Th2 immunity. GBM patient sera samples induce high levels of CD163 expression when added to normal monocytes, providing mechanistic evidence of a basis for Th2 bias. Fractionation of GBM patient sera into samples enriched for exosomes or soluble factors proved that both fractions are capable of inducing CD163 expression in normal monocytes. Conclusions The results of the current study indicate a Th2 bias in the periphery of GBM patients, likely as a result of products elaborated by the tumor. Consequentially, through immune modulation these brain tumors exert systemic effects beyond the confines of the CNS. PMID:26180083

  19. 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.

  20. Chinese preparation Xuesaitong promotes the mobilization of bone marrow mesenchymal stem cells in rats with cerebral infarction.

    PubMed

    Zhang, Jin-Sheng; Zhang, Bao-Xia; Du, Mei-Mei; Wang, Xiao-Ya; Li, Wei

    2016-02-01

    After cerebral ischemia, bone marrow mesenchymal stem cells are mobilized and travel from the bone marrow through peripheral circulation to the focal point of ischemia to initiate tissue regeneration. However, the number of bone marrow mesenchymal stem cells mobilized into peripheral circulation is not enough to exert therapeutic effects, and the method by which blood circulation is promoted to remove blood stasis influences stem cell homing. The main ingredient of Xuesaitong capsules is Panax notoginseng saponins, and Xuesaitong is one of the main drugs used for promoting blood circulation and removing blood stasis. We established rat models of cerebral infarction by occlusion of the middle cerebral artery and then intragastrically administered Xuesaitong capsules (20, 40 and 60 mg/kg per day) for 28 successive days. Enzyme-linked immunosorbent assay showed that in rats with cerebral infarction, middle- and high-dose Xuesaitong significantly increased the level of stem cell factors and the number of CD117-positive cells in plasma and bone marrow and significantly decreased the number of CD54- and CD106-positive cells in plasma and bone marrow. The effect of low-dose Xuesaitong on these factors was not obvious. These findings demonstrate that middle- and high-dose Xuesaitong and hence Panax notoginseng saponins promote and increase the level and mobilization of bone marrow mesenchymal stem cells in peripheral blood.

  1. Tissue engineering with peripheral blood-derived mesenchymal stem cells promotes the regeneration of injured peripheral nerves.

    PubMed

    Pan, Mengjie; Wang, Xianghai; Chen, Yijing; Cao, Shangtao; Wen, Jinkun; Wu, Guofeng; Li, Yuanyuan; Li, Lixia; Qian, Changhui; Qin, Zhenqi; Li, Zhenlin; Tan, Dandan; Fan, Zhihao; Wu, Wutian; Guo, Jiasong

    2017-03-07

    Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP. Furthermore, iPBMSCs seeded in an artificial nerve conduit to bridge a 10-mm defect in a sciatic nerve achieved significant nerve regeneration outcomes, including axonal regeneration and remyelination, nerve conduction recovery, and restoration of motor function, and attenuated myoatrophy and neuromuscular junction degeneration in the target muscle. Overall, the data from this study indicated that PBMSCs can transdifferentiate towards SC-like cells and have potential as grafting cells for nerve tissue engineering.

  2. Interaction between human peripheral blood monocytes and tumor promoters: Effect on growth differentiation and function in vitro

    SciTech Connect

    Keisari, Y.; Bucana, C.; Markovich, S.; Campbell, D.E. )

    1990-08-01

    Studies on the differentiation and activation of human monocytes in tissue cultures have usually been limited by the deterioration of human monocytes and macrophages in long-term cultures. In this study, we attempted to establish long-term human monocyte/macrophage cultures using the phorbol ester 12-0 tetradecanoyl-phorbol-13-acetate (TPA), and we studied the morphology, function, and biochemical properties of such treated human blood monocytes. Enriched suspensions of monocytes were obtained using Ficoll-Hypaque gradient and cultured in the absence or presence of various concentrations of TPA. Samples were removed at different times and processed for scanning electron microscopy. Parallel samples were examined for numbers of adherent cells, phagocytosis, oxidative burst, beta-galactosidase assays, and lectin-mediated erythrolysis. TPA-treated monocytes survived in larger numbers in culture for up to 7 weeks and were more pleomorphic and exhibited higher beta-galactosidase activities after 14 days in culture than untreated monocytes. TPA-treated cells and untreated cells in long-term cultures showed a decrease in their oxidative burst activity while their phagocytic activity was not affected, and the TPA treatment augmented the lysis of wheat germ agglutinin-opsonized erythrocytes by the cultured monocytes. TPA treatment of adherent human monocytes resulted in cell cultures with increased numbers of viable and functionally adherent cells for extended periods of time and does not seem to interfere with the differentiation and maturation of the cells in culture.

  3. Promoting Effects of Heparin on ex vivo Expansion of Megakaryocytopoiesis from Human Cord Blood CD34+ Cells

    PubMed Central

    Maurer, Anne-Marie; Gezer, Altay

    2013-01-01

    Summary Introduction Transfusion of ex vivo expanded megakaryocytes (MKs) has been proposed to sustain platelet recovery after cord blood (CB) hematopoietic stem cell transplantation. In this study, we investigated the effects of heparin on ex vivo colony forming unit-megakaryocytes (CFU-MKs) and MKs expansion from CB CD34+ cells. Methods CB CD34+ cells were stimulated by a combination of thrombopoietin (TPO), stem cell factor (SCF), Flt3-Ligand (FL), IL-6, and IL-11 supplemented with autologous serum and heparin during 14 days. Expanded cells were analyzed by flow cytometry and cultured in a CFU-MK assay. Results Compared to control cultures, the 5-factor combination with heparin induced significantly (p ≤ 0.05) higher numbers of: CFU-MKs and CD41+ cells on days 7 and 14; CD41+ cells displaying hyperploidy levels (≥8N) on day 14; platelets on day 14. The culture-derived platelets were activated upon collagen stimulation. Conclusion Heparin can significantly enhance the stimulating effects of a combination of TPO, SCF, FL, IL-6, and IL-11 supplemented with autologous serum on CFU-MK, MK, and platelet production from CB CD34+ cells. This expansion system could represent a promising method to generate CFU-MKs and MKs cells for transfusion to sustain platelet reconstitution following CB transplantation. PMID:24273488

  4. An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin

    PubMed Central

    Carrancio, Soraya; Markovics, Jennifer; Wong, Piu; Leisten, Jim; Castiglioni, Paola; Groza, Matthew C; Raymon, Heather K; Heise, Carla; Daniel, Tom; Chopra, Rajesh; Sung, Victoria

    2014-01-01

    Sotatercept (ACE-011), a recombinant human fusion protein containing the extracellular domain of the human Activin receptor IIA, binds to and inhibits activin and other members of the transforming growth factor -β (TGF-β) superfamily. Administration of sotatercept led to a rapid and sustained increase in red blood cell (RBC) count and haemoglobin (Hb) in healthy volunteers (phase I clinical trials), but the mechanism is not fully understood. Mice treated with RAP-011 (murine ortholog of ACE-011) respond with a rapid (within 24 h) increase in haematocrit, Hb, and RBC count. These effects are accompanied by an equally rapid stimulation of late-stage erythroid precursors in the bone marrow (BM). RAP-011 also induces a significant increase in erythroid burst-forming units and erythropoietin, which could contribute to additional, sustained effects on RBC production. Further in vitro co-culture studies demonstrate that BM accessory cells are required for RAP-011 effects. To better understand which TGF-β family ligand(s) mediate RAP-011 effects, we evaluated the impact of several of these ligands on erythroid differentiation. Our data suggest that RAP-011 may act to rescue growth differentiation factor 11/Activin A-induced inhibition of late-stage erythropoiesis. These data define the mechanism of action of a novel agent that regulates RBC differentiation and provide the rationale to develop sotatercept for the treatment of anaemia and ineffective erythropoiesis. PMID:24635723

  5. Cryptococcus neoformans activates RhoGTPase proteins followed by protein kinase C, focal adhesion kinase, and ezrin to promote traversal across the blood-brain barrier.

    PubMed

    Kim, Jong-Chul; Crary, Benjamin; Chang, Yun C; Kwon-Chung, Kyung J; Kim, Kee J

    2012-10-19

    Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. Previous studies have demonstrated that Cryptococcus binding and invasion of human brain microvascular endothelial cells (HBMEC) is a prerequisite for transmigration across the blood-brain barrier. However, the molecular mechanism involved in the cryptococcal blood-brain barrier traversal is poorly understood. In this study we examined the signaling events in HBMEC during interaction with C. neoformans. Analysis with inhibitors revealed that cryptococcal association, invasion, and transmigration require host actin cytoskeleton rearrangement. Rho pulldown assays revealed that Cryptococcus induces activation of three members of RhoGTPases, e.g. RhoA, Rac1, and Cdc42, and their activations are required for cryptococcal transmigration across the HBMEC monolayer. Western blot analysis showed that Cryptococcus also induces phosphorylation of focal adhesion kinase (FAK), ezrin, and protein kinase C α (PKCα), all of which are involved in the rearrangement of host actin cytoskeleton. Down-regulation of FAK, ezrin, or PKCα by shRNA knockdown, dominant-negative transfection, or inhibitors significantly reduces cryptococcal ability to traverse the HBMEC monolayer, indicating their positive role in cryptococcal transmigration. In addition, activation of RhoGTPases is the upstream event for phosphorylation of FAK, ezrin, and PKCα during C. neoformans-HBMEC interaction. Taken together, our findings demonstrate that C. neoformans activates RhoGTPases and subsequently FAK, ezrin, and PKCα to promote their traversal across the HBMEC monolayer, which is the critical step for cryptococcal brain infection and development of meningitis.

  6. A study of blood serotonin and serotonin transporter promoter variant (5-HTTLPR) polymorphism in Egyptian autistic children

    PubMed Central

    Meguid, Nagwa A.; Gebril, Ola H.; Khalil, Rehab O.

    2015-01-01

    Background: Autism spectrum disorder (ASD) is a complex, heterogeneous neurodevelopmental disorder with onset during early childhood. Most studies have reported an elevation in platelet serotonin in persons with autism. The serotonin (5-hydroxytryptamine; 5-HT) transporter in the brain uptakes 5-HT from extracellular spaces. It is also present in platelets, where it takes up 5-HT from plasma. Polymorphisms in serotonin transporter gene (SLC6A4) were frequently studied in many neuropsychiatric disorders. Materials and Methods: We have measured the plasma 5-HT levels in 20 autistic male children and 20 control male children by the enzyme-linked immunosorbent assay (ELISA) method. In addition, the SLC6A4 promoter region (5-HTTLPR) insertion/deletion (I/D) polymorphism was studied, using whole genomic DNA. Results: Plasma serotonin was significantly low in autistic children compared to control (P = 0.001), although correlation to severity of autism was not significant. The frequency of short (S) allele in autism cases was 10% and in the control group it was absent. Conclusion: Our study demonstrated an increased prevalence of 5-HTTLPR S allele in autism subjects. Significantly decreased plasma serotonin was detected in autism subjects, with no significant relationship between 5-HTTLPR genotype and plasma 5-HT being evident. PMID:26015920

  7. Acute and Chronic Whole-Body Vibration Exercise does not Induce Health-Promoting Effects on The Blood Profile

    PubMed Central

    Theodorou, Anastasios A.; Gerodimos, Vassilis; Karatrantou, Konstantina; Paschalis, Vassilis; Chanou, Konstantina; Jamurtas, Athanasios Z.; Nikolaidis, Michalis G.

    2015-01-01

    Whole-body vibration (WBV) exercise is an alternative, popular and easy exercise that can be followed by general public. Therefore, the aim of the present study was to investigate the influence of acute and chronic WBV exercise on health-related parameters. Twenty-eight women were allocated into a control group (n=11, mean ±SEM: age, 43.5 ±1.5 yr; body mass, 66.1 ±3.1 kg; height, 160.6 ±1.5 cm) and a vibration group (n=17, mean ±SEM: age, 44.0 ±1.0 yr; body mass, 67.1 ±2.2 kg; height, 162.5 ±1.5 cm). After baseline assessments, participants of the experimental group performed WBV training 3 times/week for 8 weeks. Before and after the chronic WBV exercise, the participants of the vibration group performed one session of acute WBV exercise. Blood chemistry measurements (hematology, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, glucose, insulin, triacylglycerols, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B and lipoprotein, thiobarbituric-acid reactive substances, protein carbonyls, total antioxidant capacity, uric acid, albumin and bilirubin) were assessed pre-exercise and post-exercise at the first and eighth week of WBV exercise in both control and vibration groups. The results failed to support any effect of both acute and chronic WBV exercise on biochemical health-related parameters. However, it seems that WBV exercise is a safe way of training without a negative impact on muscle and liver functionality. PMID:26240654

  8. Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients.

    PubMed

    Raposo, Mafalda; Bettencourt, Conceição; Ramos, Amanda; Kazachkova, Nadiya; Vasconcelos, João; Kay, Teresa; Bruges-Armas, Jácome; Lima, Manuela

    2017-03-01

    Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PCR. Moreover, the effect of APOE isoforms, known to modulate cytokines, was investigated. Correlations between cytokine variants and onset were tested; the cumulative modifier effects of cytokines and APOE were analysed. Patients carrying the IL6*C allele had a significant earlier onset (4 years in average) than patients carrying the G allele, in agreement with lower mRNA levels produced by IL6*C carriers. The presence of APOE*ɛ2 allele seems to anticipate onset in average 10 years in patients carrying the IL6*C allele; a larger number of patients will be needed to confirm this result. These results highlight the pertinence of conducting further research on the role of cytokines as SCA3 modulators, pointing to the presence of shared mechanisms involving IL6 and APOE.

  9. DNA damage in peripheral blood lymphocytes and association with polymorphisms in the promoter region of the CYP2E1 gene in alcoholics from Central Brazil.

    PubMed

    Ramos, Jheneffer Sonara Aguiar; Alves, Alessandro Arruda; Lopes, Mariana Paiva; Pedroso, Thays Millena Alves; Felício, Leandro Prado; Carvalho, Wanessa Fernandes; Franco, Fernanda Craveiro; Araújo Melo, Caroline Oliveira; Gonçalves, Macks Wendhell; Soares, Thannya Nascimento; da Cruz, Aparecido Divino; de Melo E Silva, Daniela

    2016-12-01

    DNA damage caused by the accumulation of bio-products generated in the biotransformation of ethanol to acetaldehyde mediated by the CYP2E1 enzyme has been studied. To evaluate DNA damage in peripheral blood lymphocytes and the possible association with polymorphisms in the promoter region of the CYP2E1 gene, we performed a case-control study including 75 alcoholics and 59 individuals who consume alcohol socially. Alcoholics were previously diagnosed by the Psychosocial Care Center - Alcohol and Drugs (CAPS A/D) in the city of Goiania, Goias state, Central Brazil. DNA damage was evaluated by comet assay. The analysis of the rs3813867, rs2031920, and rs2031921 polymorphisms in the promoter region of CYP2E1 gene was performed by Sanger sequencing. Men older than 35 years old were the most common alcoholics. We found increased DNA damage in the case group, compared to the control group (p < 0.001). Alcoholics who were heterozygous in the rs3813867, rs2031920, and rs2031921 polymorphisms showed higher DNA damage (tail length and olive tail moment), compared to individuals with the homozygous non-mutated allele. Previous studies have shown that polymorphisms in the promoter region of the CYP2E1 gene could cause higher CYP2E1 transcriptional activity, increasing enzyme activity compared with nondrinkers, indicating that the presence of the mutated allele (heterozygous or homozygous) may be associated with higher alcohol metabolic rates and therefore show increased acetaldehyde levels after alcohol consumption, which then can exert its carcinogenic effect.

  10. Establishment of a multimarker qPCR panel for the molecular characterization of circulating tumor cells in blood samples of metastatic breast cancer patients during the course of palliative treatment

    PubMed Central

    Bredemeier, Maren; Edimiris, Philippos; Tewes, Mitra; Mach, Pawel; Aktas, Bahriye; Schellbach, Doreen; Wagner, Jenny; Kimmig, Rainer; Kasimir-Bauer, Sabine

    2016-01-01

    Background Circulating tumor cells (CTC) are discussed to be an ideal surrogate marker for individualized treatment in metastatic breast cancer (MBC) since metastatic tissue is often difficult to obtain for repeated analysis. We established a nine gene qPCR panel to characterize the heterogeneous CTC population in MBC patients including epithelial CTC, their receptors (EPCAM, ERBB2, ERBB3, EGFR) CTC in Epithelial-Mesenchymal-Transition [(EMT); PIK3CA, AKT2), stem cell-like CTC (ALDH1) as well as resistant CTC (ERCC1, AURKA] to identify individual therapeutic targets. Results At TP0, at least one marker was detected in 84%, at TP1 in 74% and at TP2 in 79% of the patients, respectively. The expression of ERBB2, ERBB3 and ERCC1 alone or in combination with AURKA was significantly associated with therapy failure. ERBB2 + CTC were only detected in patients not receiving ERBB2 targeted therapies which correlated with no response. Furthermore, patients responding at TP2 had a significantly prolonged overall-survival than patients never responding (p = 0.0090). Patients and Methods 2 × 5 ml blood of 62 MBC patients was collected at the time of disease progression (TP0) and at two clinical staging time points (TP1 and TP2) after 8–12 weeks of chemo-, hormone or antibody therapy for the detection of CTC (AdnaTest EMT-2/StemCell Select™, QIAGEN Hannover GmbH, Germany). After pre-amplification, multiplex qPCR was performed. Establishment was performed using various cancer cell lines. PTPRC (Protein tyrosine phosphatase receptor type C) and GAPDH served as controls. Conclusions Monitoring MBC patients using a multimarker qPCR panel for the characterization of CTC might help to treat patients accordingly in the future. PMID:27223437

  11. 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.

  12. Promoter region hypermethylation and mRNA expression of MGMT and p16 genes in tissue and blood samples of human premalignant oral lesions and oral squamous cell carcinoma.

    PubMed

    Bhatia, Vikram; Goel, Madhu Mati; Makker, Annu; Tewari, Shikha; Yadu, Alka; Shilpi, Priyanka; Kumar, Sandeep; Agarwal, S P; Goel, Sudhir K

    2014-01-01

    Promoter methylation and relative gene expression of O(6)-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation of MGMT and p16 genes was observed in 59% (P = 0.0010) and 57% (P = 0.0016) of tissue samples, respectively, and 39% (P = 0.0135) and 33% (P = 0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P = 0.0001) and 82% (P = 0.0001) in tissue and 57% (P = 0.0002) and 70% (P = 0.0001) in blood, respectively. Significant downregulation of MGMT and p16 mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC.

  13. Promoter Region Hypermethylation and mRNA Expression of MGMT and p16 Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

    PubMed Central

    Bhatia, Vikram; Makker, Annu; Tewari, Shikha; Yadu, Alka; Shilpi, Priyanka; Kumar, Sandeep; Agarwal, S. P.; Goel, Sudhir K.

    2014-01-01

    Promoter methylation and relative gene expression of O6-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation of MGMT and p16 genes was observed in 59% (P = 0.0010) and 57% (P = 0.0016) of tissue samples, respectively, and 39% (P = 0.0135) and 33% (P = 0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P = 0.0001) and 82% (P = 0.0001) in tissue and 57% (P = 0.0002) and 70% (P = 0.0001) in blood, respectively. Significant downregulation of MGMT and p16 mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC. PMID:24991542

  14. Genetic engineering of platelets to neutralize circulating tumor cells.

    PubMed

    Li, Jiahe; Sharkey, Charles C; Wun, Brittany; Liesveld, Jane L; King, Michael R

    2016-04-28

    Mounting experimental evidence demonstrates that platelets support cancer metastasis. Within the circulatory system, platelets guard circulating tumor cells (CTCs) from immune elimination and promote their arrest at the endothelium, supporting CTC extravasation into secondary sites. Neutralization of CTCs in blood circulation can potentially attenuate metastases to distant organs. Therefore, extensive studies have explored the blockade of platelet-CTC interactions as an anti-metastatic strategy. Such an intervention approach, however, may cause bleeding disorders since the platelet-CTC interactions inherently rely on the blood coagulation cascade including platelet activation. On the other hand, platelets have been genetically engineered to correct inherited bleeding disorders in both animal models and human clinical trials. In this study, inspired by the physical association between platelets and CTCs, platelets were genetically modified to express surface-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a cytokine known to induce apoptosis specifically in tumor cells. The TRAIL-expressing platelets were demonstrated to kill cancer cells in vitro and significantly reduce metastases in a mouse model of prostate cancer metastasis. Our results suggest that using platelets to produce and deliver cancer-specific therapeutics can provide a Trojan-horse strategy of neutralizing CTCs to attenuate metastasis.

  15. Associations between genetic variants in the promoter region of the insulin-like growth factor-1 (IGF1) gene and blood serum IGF1 concentration in Hanwoo cattle.

    PubMed

    Chung, H Y; Choi, Y J; Park, H N; Davis, M E

    2015-04-10

    In this study, we investigated the associations between genetic variants in the promoter region of the insulin-like growth factor-1 (IGF1) gene and blood serum IGF1 concentration in Hanwoo cattle. Polymerase chain reaction primers were based on GenBank accession No. AF404761 and amplified approximately 533-bp segments. Newly identified sequences were submitted to GenBank (accession No. DQ267493). Sequence analysis revealed that genetic variants were located at a nucleotide position 323 for the nucleotide substitution C/A that was first reported in this study and positions 326-349 for a repeat motif (CA10-11). The allele frequencies of g.323C>A were 0.264 (C) and 0.736 (A) without significant deviation from Hardy-Weinberg equilibrium. Frequencies of the repeat motif CA(10) and CA(11) were 0.604 and 0.396, respectively. Statistical analysis revealed that the genetic variation g.323C>A was significantly associated with blood serum IGF1 concentrations with significant additive genetic effects, whereas no associations were found for the repeat motif. IGF1 concentrations were positively (r = 0.453) and negatively (r = -0.445) correlated with weights in the growing stages (16-21 months) and late fattening stages (22-30 months), respectively. The results of the present study and future genotypic data for Hanwoo beef cattle based on the robust genetic variation of IGF1 will provide critical information for genetic improvement and will have a large impact on commercial markets.

  16. GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer's disease model.

    PubMed

    Kim, Dong Hyun; Lee, Dahm; Chang, Eun Hyuk; Kim, Ji Hyun; Hwang, Jung Won; Kim, Ju-Yeon; Kyung, Jae Won; Kim, Sung Hyun; Oh, Jeong Su; Shim, Sang Mi; Na, Duk Lyul; Oh, Wonil; Chang, Jong Wook

    2015-10-15

    Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-β (Aβ) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB-MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Aβ42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF-15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD.

  17. Roadmap for cardiovascular circulation model.

    PubMed

    Safaei, Soroush; Bradley, Christopher P; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R; Omholt, Stig W; Chase, J Geoffrey; Müller, Lucas O; Watanabe, Sansuke M; Blanco, Pablo J; de Bono, Bernard; Hunter, Peter J

    2016-12-01

    Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well-established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo-skeletal system. The computational infrastructure for the cardiovascular model should provide for near real-time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model.

  18. Bilirubin UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene Promoter Polymorphisms and HPRT, Glycophorin A, and Micronuclei Mutant Frequencies in Human Blood

    SciTech Connect

    Grant, D; Hall, I J; Eastmond, D; Jones, I M; Bell, D A

    2004-10-06

    A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 gene (UGT1A1). The 7-TA repeat allele has been associated with elevated serum bilirubin levels that cause a mild hyperbilirubinemia (Gilbert's syndrome). Studies suggest that promoter transcriptional activity of UGT1A1 is inversely related to the number of TA repeats and that unconjugated bilirubin concentration increases directly with the number of TA repeat elements. Because bilirubin is a known antioxidant, we hypothesized that UGT1A1 repeats associated with higher bilirubin may be protective against oxidative damage. We examined the effect of UGT1A1 genotype on somatic mutant frequency in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene in human lymphocytes and the glycophorin A (GPA) gene of red blood cells (both N0, NN mutants), and the frequency of lymphocyte micronuclei (both kinetochore (K) positive or micronuclei K negative) in 101 healthy smoking and nonsmoking individuals. As hypothesized, genotypes containing 7-TA and 8-TA displayed marginally lower GPA{_}NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7-TA and 8-TA) were associated with modestly increased HPRT mutation frequency (p<0.05) while the same low expression genotypes were not significantly associated with micronuclei frequencies (K-positive or K-negative) when compared to high expression genotypes (5-TA and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7-TA and 8-TA were associated with increased GPA{_}N0 mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). These data suggest that UGT1A1 genotype may modulate somatic mutation of some types, in some cell lineages, by a mechanism not involving bilirubin antioxidant activity. More detailed studies examining UGT1A1 promoter variation, oxidant/antioxidant balance and genetic

  19. 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.

  20. Interaction between endometrial epithelial cells and blood leucocytes promotes cytokine release and epithelial barrier function in response to Chlamydia trachomatis lipopolysaccharide stimulation.

    PubMed

    Sze Ho, Lok; He, Qiong; Chen, Jie; Xu, Penghui; Ling Tsang, Lai; Yu, Sidney; Wa Chung, Yiu; Chang Chan, Hsiao

    2010-09-01

    Chlamydia trachomatis infection is currently the most common cause of infection-related sterility in women. However, it remains largely unknown how uterine epithelial cells interact with recruited leucocytes in response to C. trachomatis infection in the female genital tract. To study the defence mechanism of the endometrium against C. trachomatis infection, we established an in vitro co-culture of EEC (endometrial epithelial cells) and PBL (peripheral blood leucocytes) isolated from mice and investigated the immune response of these cells upon C. trachomatis LPS (lipopolysaccharide) challenge using a cytokine antibody array and RT-PCR (reverse transcription-PCR). Our results showed that upon C. trachomatis LPS stimulation, proinflammatory cytokines/chemokines, such as TNF-alpha, IL-1beta, MIPs (macrophage inflammatory proteins), IL-12p40p70, KC, GCSFs (granulocyte colony stimulating factors), IL-6 and TIMPs (tissue inhibition metalloproteinases) are up-regulated and/or released from EEC-PBL co-culture. Further, the TER (transepithelial resistance), measured by the Isc (short-circuit current) technique was significantly increased in EEC/PBL co-cultured cells and also when stimulated with C. trachomatis LPS compared with EEC alone. These changes appear to be mediated by the change in cytokine-induced expression of tight junction-related protein ZO-1. The present results demonstrated that the epithelial-immune cross-talk could promote the release of proinflammatory cytokines and enhance the barrier function of the endometrium against C. trachomatis infection in the female reproductive tract.

  1. Chronic low-level arsenite exposure through drinking water increases blood pressure and promotes concentric left ventricular hypertrophy in female mice.

    PubMed

    Sanchez-Soria, Pablo; Broka, Derrick; Monks, Sarah L; Camenisch, Todd D

    2012-04-01

    Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding of how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressure. Echocardiographic analyses as well as histological assessment show concentric left ventricular hypertrophy, a primary cardiac manifestation of chronic hypertension. Live imaging by echocardiography shows a 43% increase in left ventricular mass in arsenic-treated animals. Relative wall thickness (RWT) was calculated showing that all the arsenic-exposed animals show an RWT greater than 0.45, indicating concentric hypertrophy. Importantly, left ventricular hypertrophy, although often associated with chronic hypertension, is an independent risk factor for cardiovascular-related mortalities. These results suggest that chronic low-level arsenite exposure promotes the development of hypertension and the comorbidity of concentric hypertrophy.

  2. Evaluation of Aloe vera and synbiotic as antibiotic growth promoter substitutions on performance, gut morphology, immune responses and blood constitutes of broiler chickens.

    PubMed

    Naghi Shokri, Ali; Ghasemi, Hossein A; Taherpour, Kamran

    2017-02-01

    This study was performed to investigate the effect of dietary supplementation with Aloe vera (AV) powder and synbiotic as growth promoter agents on performance, gut morphology, immune responses, hematology and serum biochemistry in broilers. A total of 240-day-old male broiler chicks (Ross 308) were randomly assigned to six treatments with four replicates. Birds were offered either a corn-soybean meal basal diet (control) or the basal diet supplemented with 200 mg/kg virginiamycin (VM), 1 g/kg synbiotic (Syn), 2.5 g/kg AV (AV1), 5.0 g/kg AV (AV2) or 7.5 g/kg AV (AV3). Chickens fed any of the diets, except diet AV1, exhibited better feed conversion ratios at the 14-28 day period and higher average daily gain and duodenal villus height/crypt depth ratio at 42 days than those fed the control diet. Synbiotic supplementation caused a marked increase in the serum antibody titer against infectious bursal disease and infectious bronchitis vaccines. Feeding diet AV3 significantly increased red blood cell count and hemoglobin concentration, and decreased serum triglyceride level compared to the control group. The results suggested that dietary inclusion of 5 and 7.5 g/kg AV, similar with synbiotic supplementation, can be applied as effective alternatives to in-feed antibiotics for broiler diets.

  3. Twenty-five years of peripheral blood stem cell transplantation.

    PubMed

    Körbling, Martin; Freireich, Emil J

    2011-06-16

    Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. Its clinical introduction in 1986 replaced BM as a stem-cell source to approximately 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis technology, the discovery of hematopoietic growth factors and small molecule CXCR4 antagonist for stem- cell mobilization, and in vivo experimental transplantation studies that eventually led to clinical PBSCT. Also mentioned are the controversies surrounding the engraftment potential of circulating stem cells before acceptance as a clinical modality. Clinical trials comparing the outcome of PBSCT with BM transplantation, registry data analyses, and the role of the National Marrow Donor Program (NMDP) in promoting unrelated blood stem-cell donation are addressed.

  4. 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

  5. Blood sugar test - blood

    MedlinePlus

    ... sugar; Blood sugar level; Fasting blood sugar; Glucose test; Diabetic screening - blood sugar test; Diabetes - blood sugar test ... The test may be done in the following ways: After you have not eaten anything for at least 8 ...

  6. Efficacy of a meal-replacement program for promoting blood lipid changes and weight and body fat loss in US Army soldiers.

    PubMed

    Smith, Tracey J; Sigrist, Lori D; Bathalon, Gaston P; McGraw, Susan; Karl, J Philip; Young, Andrew J

    2010-02-01

    Excess weight is associated with negative health outcomes. Meal replacements are effective in promoting favorable body composition changes in civilian populations; however, their efficacy with military service members who have unique lifestyles is unknown. The objective of this randomized controlled trial was to determine the efficacy of the Army's education-based weight-management program, "Weigh to Stay," with and without meal replacements for improving blood lipids, and to promote weight and body fat loss in overweight US Army soldiers. Soldiers (n=113; 76 males/37 females) attending Weigh to Stay at Fort Bragg, NC, in 2006/2007 were randomized to Weigh to Stay only or a commercially available meal-replacement program (two meal replacements per day) in conjunction with Weigh to Stay, and followed until Army body fat standards were met or for 6 months if standards were not met. Study completers (n=46) in both treatment groups lost weight (Weigh to Stay: -2.7+/-4.3 kg; meal replacers: -3.8+/-3.5 kg) and fat mass (Weigh to Stay, -2.7+/-3.2 kg; meal replacers: -2.9+/-2.5 kg), and improved high-density lipoprotein cholesterol concentrations (Weigh to Stay: 13+/-9 mg/dL [0.34+/-0.23 mmol/L]; meal replacers: 8+/-7 mg/dL [0.21+/-0.18 mmol/L]; P<0.05); however, no between-group differences were observed. Attrition was lower (P=0.009) and success in meeting body fat standards tended to be higher (P=0.06) for the meal replacers vs Weigh to Stay participants. Intent-to-treat analysis demonstrated that meal replacers lost more weight (1.2+/-0.5 kg), percent body fat (1.0%+/-0.4%), and fat mass (0.8+/-0.4 kg) compared to Weigh to Stay volunteers (P<0.05). Our findings suggest that meal replacement use can be recommended as a potential adjunct strategy to Weigh to Stay.

  7. 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…

  8. Short term ex-vivo expansion of circulating head and neck tumour cells

    PubMed Central

    Kulasinghe, Arutha; Perry, Chris; Warkiani, Majid E.; Blick, Tony; Davies, Anthony; O'Byrne, Ken; Thompson, Erik W.; Nelson, Colleen C.; Vela, Ian; Punyadeera, Chamindie

    2016-01-01

    Minimally invasive techniques are required for the identification of head and neck cancer (HNC) patients who are at an increased risk of metastasis, or are not responding to therapy. An approach utilised in other solid cancers is the identification and enumeration of circulating tumour cells (CTCs) in the peripheral blood of patients. Low numbers of CTCs has been a limiting factor in the HNC field to date. Here we present a methodology to expand HNC patient derived CTCs ex-vivo. As a proof of principle study, 25 advanced stage HNC patient bloods were enriched for circulating tumour cells through negative selection and cultured in 2D and 3D culture environments under hypoxic conditions (2% O2, 5% CO2). CTCs were detected in 14/25 (56%) of patients (ranging from 1–15 CTCs/5 mL blood). Short term CTC cultures were successfully generated in 7/25 advanced stage HNC patients (5/7 of these cultures were from HPV+ patients). Blood samples from which CTC culture was successful had higher CTC counts (p = 0.0002), and were predominantly from HPV+ patients (p = 0.007). This is, to our knowledge, the first pilot study to culture HNC CTCs ex-vivo. Further studies are warranted to determine the use of short term expansion in HNC and the role of HPV in promoting culture success. PMID:27517751

  9. Local sustained delivery of acetylsalicylic acid via hybrid stent with biodegradable nanofibers reduces adhesion of blood cells and promotes reendothelialization of the denuded artery.

    PubMed

    Lee, Cheng-Hung; Lin, Yu-Huang; Chang, Shang-Hung; Tai, Chun-Der; Liu, Shih-Jung; Chu, Yen; Wang, Chao-Jan; Hsu, Ming-Yi; Chang, Hung; Chang, Gwo-Jyh; Hung, Kuo-Chun; Hsieh, Ming-Jer; Lin, Fen-Chiung; Hsieh, I-Chang; Wen, Ming-Shien; Huang, Yenlin

    2014-01-01

    Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a highperformance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.

  10. Neuropeptide Y promoter polymorphism modifies effects of a weight-loss diet on 2-year changes of blood pressure: the preventing overweight using novel dietary strategies trial.

    PubMed

    Zhang, Xiaomin; Qi, Qibin; Liang, Jun; Hu, Frank B; Sacks, Frank M; Qi, Lu

    2012-11-01

    Neuropeptide Y (NPY) is implicated in the regulation of blood pressure (BP), and NPY pathways in the hypothalamus are sensitive to dietary fat. We evaluated the potential effect of a functional variant rs16147 located in the NPY gene promoter region on the association between 2-year diet intervention and change in multiple BP measures in the randomized Preventing Overweight Using Novel Dietary Strategies Trial. The NPY rs16147 was genotyped in 723 obese adults who were randomly assigned to 1 of 4 diets differing in the target percentages of energy derived from fat, protein, and carbohydrate. The changes of 4 BP phenotypes, including systolic BP, diastolic BP, pulse pressure, and mean arterial pressure, during 2-year diet intervention were analyzed. In the total participants and participants with hypertension, we observed significant and consistent interactions between rs16147 genotype and dietary fat intake on changes in multiple BP phenotypes at 2 years (all P for interactions <0.05). The risk allele (C allele) was associated with a greater reduction of BP phenotypes in response to low-fat diet, whereas an opposite genetic effect was observed in response to high-fat diet. In addition, the C allele was related to greater changes in 4 BP phenotypes in hypertensive compared with nonhypertensive participants. Our data suggest that NPY rs16147 may modulate the association between dietary fat intake and changes in BP phenotypes, and the C allele exerts a long-term beneficial effect on lowering BP in response to low-fat diet in obese and hypertensive subjects.

  11. A Perspective on Promoting Diversity in the Biomedical Research Workforce: The National Heart, Lung, and Blood Institute’s PRIDE Program

    PubMed Central

    Boyington, Josephine E.A.; Maihle, Nita J.; Rice, Treva K.; Gonzalez, Juan E.; Hess, Caryl A.; Makala, Levi H.; Jeffe, Donna B.; Ogedegbe, Gbenga; Rao, Dabeeru C.; Dávila-Román, Victor G.; Pace, Betty S.; Jean-Louis, Girardin; Boutjdir, Mohamed

    2016-01-01

    Aspiring junior investigators from groups underrepresented in the biomedical sciences face various challenges as they pursue research independence. However, the biomedical research enterprise needs their participation to effectively address critical research issues such as health disparities and health inequities. In this article, we share a research education and mentoring initiative that seeks to address this challenge: Programs to Increase Diversity among Individuals Engaged in Health Related Research (PRIDE), funded by the National Heart, Lung, and Blood Institute (NHLBI). This longitudinal research-education and mentoring program occurs through summer institute programs located at US-based academic institutions. Recruited participants are exposed to didactic and lab-based research-skill enhancement experiences, with year-round mentoring over the course of two years. Mentor-mentee matching is based on shared research interests to promote congruence and to enhance skill acquisition. Program descriptions and sample narratives of participants’ perceptions of PRIDE’s impact on their career progress are showcased. Additionally, we highlight the overall program design and structure of four of seven funded summer institutes that focus on cardiovascular disease, related conditions, and health disparities. Mentees’ testimonials about the value of the PRIDE mentoring approach in facilitating career development are also noted. Meeting the clinical and research needs of an increasingly diverse US population is an issue of national concern. The PRIDE initiative, which focuses on increasing research preparedness and professional development of groups underrepresented in the biomedical research workforce, with an emphasis on mentoring as the critical approach, provides a robust model that is impacting the careers of future investigators. PMID:27440978

  12. 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.

  13. Blood typing

    MedlinePlus

    ... ABO blood typing; Blood group; Anemia - immune hemolytic blood type; ABO blood type; A blood type; AB blood type; O blood type ... The 2 steps above can accurately determine your blood type. Rh typing uses a method similar to ABO ...

  14. Dynamics of blood flow in a microfluidic ladder network

    NASA Astrophysics Data System (ADS)

    Maddala, Jeevan; Zilberman-Rudenko, Jevgenia; McCarty, Owen

    The dynamics of a complex mixture of cells and proteins, such as blood, in perturbed shear flow remains ill-defined. Microfluidics is a promising technology for improving the understanding of blood flow under complex conditions of shear; as found in stent implants and in tortuous blood vessels. We model the fluid dynamics of blood flow in a microfluidic ladder network with dimensions mimicking venules. Interaction of blood cells was modeled using multiagent framework, where cells of different diameters were treated as spheres. This model served as the basis for predicting transition regions, collision pathways, re-circulation zones and residence times of cells dependent on their diameters and device architecture. Based on these insights from the model, we were able to predict the clot formation configurations at various locations in the device. These predictions were supported by the experiments using whole blood. To facilitate platelet aggregation, the devices were coated with fibrillar collagen and tissue factor. Blood was perfused through the microfluidic device for 9 min at a physiologically relevant venous shear rate of 600 s-1. Using fluorescent microscopy, we observed flow transitions near the channel intersections and at the areas of blood flow obstruction, which promoted larger thrombus formation. This study of integrating model predictions with experimental design, aids in defining the dynamics of blood flow in microvasculature and in development of novel biomedical devices.

  15. 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

  16. Splenic release of platelets contributes to increased circulating platelet size and inflammation after myocardial infarction.

    PubMed

    Gao, Xiao-Ming; Moore, Xiao-Lei; Liu, Yang; Wang, Xin-Yu; Han, Li-Ping; Su, Yidan; Tsai, Alan; Xu, Qi; Zhang, Ming; Lambert, Gavin W; Kiriazis, Helen; Gao, Wei; Dart, Anthony M; Du, Xiao-Jun

    2016-07-01

    Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, β1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation.

  17. Circulation Systems on Microcomputers.

    ERIC Educational Resources Information Center

    Carlson, Gary

    1984-01-01

    Reports on the use of microcomputers in comprehensive library circulation systems. Topics covered include system requirements (reliability, completeness); determining circulation system needs (saving money, improving service, modernization); limitations of microcomputers (capacity, kinds of data stored, number of stations or terminals); system…

  18. Regulation of the pulmonary circulation in the fetus and newborn.

    PubMed

    Gao, Yuansheng; Raj, J Usha

    2010-10-01

    During the development of the pulmonary vasculature in the fetus, many structural and functional changes occur to prepare the lung for the transition to air breathing. The development of the pulmonary circulation is genetically controlled by an array of mitogenic factors in a temporo-spatial order. With advancing gestation, pulmonary vessels acquire increased vasoreactivity. The fetal pulmonary vasculature is exposed to a low oxygen tension environment that promotes high intrinsic myogenic tone and high vasocontractility. At birth, a dramatic reduction in pulmonary arterial pressure and resistance occurs with an increase in oxygen tension and blood flow. The striking hemodynamic differences in the pulmonary circulation of the fetus and newborn are regulated by various factors and vasoactive agents. Among them, nitric oxide, endothelin-1, and prostaglandin I(2) are mainly derived from endothelial cells and exert their effects via cGMP, cAMP, and Rho kinase signaling pathways. Alterations in these signaling pathways may lead to vascular remodeling, high vasocontractility, and persistent pulmonary hypertension of the newborn.

  19. 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.

  20. 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

  1. Human umbilical cord blood mononuclear cells and chorionic plate-derived mesenchymal stem cells promote axon survival in a rat model of optic nerve crush injury.

    PubMed

    Chung, Sokjoong; Rho, Seungsoo; Kim, Gijin; Kim, So-Ra; Baek, Kwang-Hyun; Kang, Myungseo; Lew, Helen

    2016-05-01

    The use of mesenchymal stem cells (MSCs) in cell therapy in regenerative medicine has great potential, particularly in the treatment of nerve injury. Umbilical cord blood (UCB) reportedly contains stem cells, which have been widely used as a hematopoietic source and may have therapeutic potential for neurological impairment. Although ongoing research is dedicated to the management of traumatic optic nerve injury using various measures, novel therapeutic strategies based on the complex underlying mechanisms responsible for optic nerve injury, such as inflammation and/or ischemia, are required. In the present study, a rat model of optic nerve crush (ONC) injury was established in order to examine the effects of transplanting human chorionic plate-derived MSCs (CP‑MSCs) isolated from the placenta, as well as human UCB mononuclear cells (CB-MNCs) on compressed rat optic nerves. Expression markers for inflammation, apoptosis, and optic nerve regeneration were analyzed, as well as the axon survival rate by direct counting. Increased axon survival rates were observed following the injection of CB‑MNCs at at 1 week post-transplantation compared with the controls. The levels of growth-associated protein-43 (GAP‑43) were increased after the injection of CB‑MNCs or CP‑MSCs compared with the controls, and the expression levels of hypoxia-inducible factor-1α (HIF-1α) were also significantly increased following the injection of CB-MNCs or CP-MSCs. ERM-like protein (ERMN) and SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) were found to be expressed in the optic nerves of the CP‑MSC-injected rats with ONC injury. The findings of our study suggest that the administration of CB‑MNCs or CP‑MSCs may promote axon survival through systemic concomitant mechanisms involving GAP‑43 and HIF‑1α. Taken together, these findings provide further understanding of the mechanisms repsonsible for optic nerve injury and may aid in the development of novel cell

  2. Human umbilical cord blood mononuclear cells and chorionic plate-derived mesenchymal stem cells promote axon survival in a rat model of optic nerve crush injury

    PubMed Central

    CHUNG, SOKJOONG; RHO, SEUNGSOO; KIM, GIJIN; KIM, SO-RA; BAEK, KWANG-HYUN; KANG, MYUNGSEO; LEW, HELEN

    2016-01-01

    The use of mesenchymal stem cells (MSCs) in cell therapy in regenerative medicine has great potential, particularly in the treatment of nerve injury. Umbilical cord blood (UCB) reportedly contains stem cells, which have been widely used as a hematopoietic source and may have therapeutic potential for neurological impairment. Although ongoing research is dedicated to the management of traumatic optic nerve injury using various measures, novel therapeutic strategies based on the complex underlying mechanisms responsible for optic nerve injury, such as inflammation and/or ischemia, are required. In the present study, a rat model of optic nerve crush (ONC) injury was established in order to examine the effects of transplanting human chorionic plate-derived MSCs (CP-MSCs) isolated from the placenta, as well as human UCB mononuclear cells (CB-MNCs) on compressed rat optic nerves. Expression markers for inflammation, apoptosis, and optic nerve regeneration were analyzed, as well as the axon survival rate by direct counting. Increased axon survival rates were observed following the injection of CB-MNCs at at 1 week post-transplantation compared with the controls. The levels of growth-associated protein-43 (GAP-43) were increased after the injection of CB-MNCs or CP-MSCs compared with the controls, and the expression levels of hypoxia-inducible factor-1α (HIF-1α) were also significantly increased following the injection of CB-MNCs or CP-MSCs. ERM-like protein (ERMN) and SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) were found to be expressed in the optic nerves of the CP-MSC-injected rats with ONC injury. The findings of our study suggest that the administration of CB-MNCs or CP-MSCs may promote axon survival through systemic concomitant mechanisms involving GAP-43 and HIF-1α. Taken together, these findings provide further understanding of the mechanisms repsonsible for optic nerve injury and may aid in the development of novel cell-based therapeutic strategies with

  3. Effects of a 10-Day Intensive Health Promotion Program Combining Diet and Physical Activity on Body Composition, Physical Fitness, and Blood Factors of Young Adults: A Randomized Pilot Study.

    PubMed

    Lee, Kyoung Soon; Lee, Jae Koo; Yeun, Young Ran

    2017-04-11

    BACKGROUND A lifestyle characterized by poor eating habits and physical inactivity is a risk factor for multiple lifestyle diseases in young adults. This study assessed the effects of implementing an intensive 10-day health promotion program combining diet and physical activities on body composition, physical fitness, and biochemical parameters of young adults. MATERIAL AND METHODS In this randomized pilot study, 30 female undergraduate students were randomly allocated to an intervention and a control group. The health promotion program consisted of unlimited amounts of vegetarian food; aerobic, flexibility, and strength exercises (3 hours/day); lectures on health (3 hours/day); massage practice (2 hours/day); and healthy cooking practice (1 hour/day). The effects of the intervention were analyzed using the Mann-Whitney U test and the Wilcoxon signed-rank test. RESULTS The intensive 10-day health promotion program significantly reduced body weight, body mass index, triglyceride, total cholesterol, low-density lipoprotein cholesterol, blood glucose, and the homeostasis model assessment of insulin resistance. At the same time, participants demonstrated increased back muscle, leg muscle, and grip strength; waist and shoulder flexibility; balance; and cardiorespiratory endurance. CONCLUSIONS The intensive 10-day health promotion program is a viable intervention for improving body composition, physical fitness, glycemic control, and blood lipid levels in young adults.

  4. Donating Blood

    MedlinePlus

    ... blood transfusion. Blood donors — especially donors with certain blood types — are always in demand. Who Can Donate Blood? ... Natural Disasters: How to Help Blood Blood Transfusions Blood Types Contact Us Print Resources Send to a Friend ...

  5. [Contributions of the Council of Europe's Blood Transfusion Steering Committee to the determination of rules for the selection of donors of blood and blood components and the study of sexual behaviors having an impact on blood safety].

    PubMed

    Behr-Gross, M-E; Heiden, M; Norda, R

    2013-05-01

    In November 2009, the Council of Europe's Blood Transfusion Steering Committee created a group of experts to explore the problem of behaviors having an impact on the management of donors of blood and blood components and on blood transfusion safety in Europe. This ad hoc group sought a harmonised interpretation of temporary exclusion (or temporary deferral), as opposed to permanent exclusion (or permanent deferral), in the context of the selection of donors of blood and blood components. It was also given the mandate to assess, on the basis of available data, the possibility of differentiating "at risk" behaviours from behaviours "at high risk" of contamination by serious infectious diseases transmitted by blood, blood components or derived therapeutic products. The primary objective of this work was to ensure the safety of blood, blood components and derived therapeutic products for future recipients by promoting a risk analysis-based approach, given that some countries envisaged amending their provisions for donor selection. However, a risk analysis can only be performed on groups, not individuals, which may give the impression of a discriminatory approach, so it needed to be justified in the context of transfusion safety. A collaborative project, which included an investigation phase, led to the drafting of a technical memorandum that summarised the data collected in ten Council of Europe member states on the selection criteria for blood donors and the epidemiology of infectious diseases (with a focus on human immunodeficiency virus) in the general population and among blood donors. The technical memorandum was published in 2011 on the European Directorate for the Quality of Medicines and Healthcare website dedicated to this project. A draft resolution of the Committee of Ministers of the Council of Europe was then developed by the Council of Europe's Blood Transfusion Steering Committee. This text was circulated among member and observer states of the Council

  6. 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)

  7. 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

  8. Congenital cardiovascular malformations and the fetal circulation.

    PubMed

    Rudolph, A M

    2010-03-01

    After birth, gas exchange is achieved in the lung, whereas prenatally it occurs in the placenta. This is associated with differences in blood flow patterns in the fetus as compared with the postnatal circulation. Congenital cardiovascular malformations are associated with haemodynamic changes in the fetus, which differ from those occurring postnatally. Obstruction to cardiac outflow may alter myocardial development, resulting in progressive ventricular hypoplasia. Alteration of oxygen content may profoundly influence pulmonary vascular and ductus arteriosus responses. Interference in blood flow and oxygen content may affect cerebral development as a result of inadequate oxygen or energy substrate supply. The circulatory effects may be gestational dependent, related to maturation of vascular responses in different organs. These prenatal influences of congenital cardiac defects may severely affect immediate, as well as longterm, postnatal prognosis and survival. This has stimulated the development of techniques for palliation of disturbed circulation during fetal life.

  9. 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

  10. Cerebral circulation during acceleration stress

    NASA Astrophysics Data System (ADS)

    Cirovic, Srdjan

    A mathematical model of the cerebrovascular system has been developed to examine the influence of acceleration on cerebral circulation. The objective is to distinguish the main factors that limit cerebral blood flow in pilots subjected to accelerations which exceed the gravitational acceleration of the earth (Gz > 1). The cerebrovascular system was approximated by an open-loop network of elastic tubes and the flow in blood vessels was modeled according to a one-dimensional theory of flow in collapsible tubes. Since linear analysis showed that the speed of pulse propagation in the intracranial vessels should not be modified by the skull constraint, the same governing equations were used for the intracranial vessels as for the rest of the network. The steady and pulsatile components of the cerebrospinal fluid pressure were determined from the condition that the cranial volume must be conserved. After the qualitative aspects of the model results were verified experimentally, the open-loop geometry was incorporated into a global mathematical model of the cardiovascular system. Both the mathematical models and the experiment show that cerebral blood flow diminishes for Gz > 1 due to an increase in the resistance of the large veins in the neck, which collapse as soon as the venous pressure becomes negative. In contrast, the conservation of the cranial volume requires that the cerebrospinal and venous pressure always be approximately the same, and the vessels contained in the cranial cavity do not collapse. Positive pressure breathing provides protection by elevating blood arterial and venous pressures at the heart, thus preventing the venous collapse and maintaining the normal cerebral vascular resistance.

  11. 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.

  12. Circulating and tissue biomarkers in early-stage non-small cell lung cancer

    PubMed Central

    Fumagalli, Caterina; Bianchi, Fabrizio; Raviele, Paola Rafaniello; Vacirca, Davide; Bertalot, Giovanni; Rampinelli, Cristiano; Lazzeroni, Matteo; Bonanni, Bernardo; Veronesi, Giulia; Fusco, Nicola; Barberis, Massimo; Guerini-Rocco, Elena

    2017-01-01

    Objective We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). Materials and Methods Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test). Promoter methylation status of p16, RASSF1a and RARβ2 and telomerase activity were assessed in sputum samples. DNA was extracted from each tumour developed during follow-up and subjected to a mutation survey using the LungCarta panel on the Sequenom MassARRAY platform. Results During follow-up (9 years) six individuals underwent surgery for stage I NSCLC with a median time of disease onset of 20.5 months. MiR-Test scores were positive (range: 0.14–7.24) in four out of six baseline pre-disease onset sera. No association was identified between free circulating DNA or sputum biomarkers and disease onset. All tumours harboured at least one somatic mutation in well-known cancer genes, including KRAS (n = 4), BRAF (n = 1), and TP53 (n = 3). Conclusion Circulating miRNA tests may represent valuable tools to detect clinically-silent tumours. Early-stage lung adenocarcinomas harbour recurrent genetic events similar to those described in advanced-stage NSCLCs. PMID:28194229

  13. Regulation of