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Sample records for promoting blood circulation

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

    PubMed

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

    2014-08-01

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

  2. Chinese Herb and Formulas for Promoting Blood Circulation and Removing Blood Stasis and Antiplatelet Therapies

    PubMed Central

    Liu, Yue; Yin, Hui-Jun; Shi, Da-zhuo; Chen, Ke-ji

    2012-01-01

    Atherothrombosis, which directly threatens people's health and lives, is the main cause of morbidity and mortality all over the world. Platelets play a key role in the development of acute coronary syndromes (ACSs) and contribute to cardiovascular events. Oral antiplatelet drugs are a milestone in the therapy of cardiovascular atherothrombotic diseases. In recent years, many reports have shown the possibility that “resistance” to oral anti-platelet drugs and many adverse reactions, such as serious bleeding risk, which provides an impetus for developing new anti-platelet drugs possesses highly efficiency and fewer adverse effects. Study on the blood stasis syndrome and promoting blood circulation and removing blood stasis is the most active field of research of integration of traditional and western medicine in China. Blood-stasis syndrome and platelet activation have close relationship, many Chinese herb and formulas for promoting blood circulation and removing blood stasis possess definite anti-platelet effect. This paper covers the progress of anti-platelet mechanism of Chinese herb and formulas for promoting blood circulation and removing blood stasis and is to be deeply discussed in further research. PMID:22454656

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

    PubMed

    Yao, Jun

    2015-04-01

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

  4. [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.

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

    PubMed

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

    2012-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Clinical effect of Jiutengzhuyu tablets on promoting blood circulation in women with oviducal obstruction.

    PubMed

    Pang, Baozhen; Pang, Qingyang; Pang, Huiqing; Song, Guohong

    2012-12-01

    To test the clinical curative effect of Jiutengzhuyu tablets, a patented Chinese vine-derived drug used for promoting blood circulation, on women with oviducal obstruction. Patients with tubal infertility were divided randomly into two groups: 58 patients in the treatment group and 57 in a control group. The treated patients took Jiutengzhuyu tablets orally for 25 days. The control group received an intrauterine infusion of 5 mg dexamethasone sodium phosphate, 4000 units of chymotrypsin, 80 000 units of gentamicin sulfate dissolved in 20 mL of normal saline at 1 mL/min. After 3 months of treatment, the curative effect on tubal patency was assessed and a 1-year follow-up visit was used to document any pregnancies. The total effective rate was 78% in the treatment group and 32% in the control group with a statistically significant difference (chi2 = 24.57, P < 0.01). Jiutengzhuyu was effective in treating infertility caused by tubal infertility with a Traditional Chinese Medicine diagnosis of blood stasis.

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

    PubMed Central

    Wang, Jie; Xiong, Xingjiang; Feng, Bo

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. [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.

  11. Effects and Perspectives of Chinese Patent Medicines for Tonifying Qi and Promoting Blood Circulation on Patients with Cerebral Infarction.

    PubMed

    Zhou, Li; Guo, Sheng-Nan; Gao, Ying

    2015-01-01

    Stroke is a disease with high morbidity, disability, and fatality. Since ischemic stroke is the most common kind of stroke, increasing attention has been paid to its prevention and treatment. Given the limitations of conventional medicine, there is growing interest in Chinese Medicine (CM), especially Chinese Patent Medicine (CPM) for its convenience and stability. Studies of CM show that Chinese Patent Medicines for Tonifying Qi and Promoting Blood Circulation (CPMs-TQPBC) are one of the most common and effective categories of all clinical CPMs in China. This review investigated and summarized the randomized controlled trials (RCT) of CPMs-TQPBC combined with conventional interventions in the last 10 years. Trial results demonstrated the potential in reducing the endpoints and improving neurologic impairments, body movements, Barthel index, quality of life, and certain biomarkers. Furthermore, certain CM syndromes were alleviated with rare adverse events. Advantages of interventions combined with CPMs-TQPBC for patients with cerebral infarction were discovered. Compared with the Chinese patent medicines for promoting blood circulation (CPMs-PBC) alone, CPMs for both tonifying qi and promoting blood circulation exhibited noticeably better effects. The underlying reasons could be related to the improvement of microcirculation in the brain, protection against ischemic reperfusion injury, generation of neuroprotective factors, and inhibition of apoptosis. Under the circumstances of qi deficiency and blood stasis syndrome (QDBSS) (Qixu-Xueyu Zheng), CPMs- TQPBC showed a substantial difference. More trials focusing on specific patient groups should be carried out to corroborate and expand the findings.

  12. 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

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

    PubMed

    Liu, Ming; Liu, Zhen

    2012-11-01

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

  14. Effects of replenishing qi, promoting blood circulation and resolving phlegm on vascular endothelial function and blood coagulation system in senile patients with hyperlipemia.

    PubMed

    Yang, Huimin; Han, Libei; Sheng, Tong; He, Qiong; Liang, Jinpu

    2006-06-01

    To observe the curative effect of the method of replenishing qi, promoting blood circulation and resolving phlegm on senile hyperlipemia and its effects on vascular endothelial function and blood coagulation system. 96 patients with senile hyperlipemia were randomly divided into a treatment group and a control group. 56 patients in the treatment group orally took danshen jueming granules while 40 patients in the control group orally took xuezhikang capsules. Observed were indexes of blood lipid, vascular endothelial function, blood coagulation system and safety. After treatment, the treatment group was obviously superior to the control group (P < 0.05) in reducing plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as well as in the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), D-dimer (D-D) and fibrinogen (FIB). Danshen Jueming Granules have the effect of regulating metabolism of blood lipid, and improving vascular endothelial function and blood coagulation system in senile patients with hyperlipemia.

  15. [Case-control study on therapeutic effects of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries].

    PubMed

    Li, Sheng-hua; Li, Yu-ji; Li, Shen-song; Deng, Qiang; Liu, Yong-ming; Kong, Ling-Jun; Zhu, Huan-ping; Liao, Min-jie

    2011-09-01

    To observe the effects of Chinese herb of promoting blood circulation to dissipate blood stasis on the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum of patients with mudslide injuries, and investigate the mechanisms of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries. Patients with mudslide injuries who were translated from Zhouqu and Chengxian to Lanzhou from 12th August 2010 were divided into two groups (group A and group B). Twenty-five patients in group A, containing 15 males and 10 females, with an average age of (39.0 +/- 3.9) years. According to AIS scoring system, 1 point in 2 cases, 2 points in 3, 3 points in 17 and 4 points in 3. No patients got 5 points. Based on ISS rating system, 16 cases got 16 points or less, 7 cases rated between 16 and 25, only 2 cases were equal to 25 points or more. Another 25 patients were in group B, including 11 males and 14 females, with a mean age of (40.1 +/- 3.6) years; AIS score showed 3 cases got 1 point, 4 got 2 points, 16 got 3 and 2 got 4 points, no patients got 5 points. Patients in group B were divided into three parts by ISS score:15 cases (16 points or less); 9 cases (range 16 to 25 points) and 1 case (25 points or more). All the patients accepted general physical checkup. Eight patients were treated by surgical treatment in group A (3 patients were treated with open reduction plate fixation, 4 patients were treated with debridement BHID, and 1 patient underwent foreign body removal) and 6 cases in group B (1 patient was treated with craniocerebral surgery,2 patients were treated with chest surgery, and 3 patients were treated with soft tissue debridement). All the patients of two groups were treated by support treatment, detumescence treatment and preventing infection, complications. A seven days course of treatment with detumescence analgesic mixture 50 ml p.o. bid, traumatologic cleansing liquid 20 ml ad us, ext 20

  16. 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.

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

    PubMed Central

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

    2010-01-01

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

  18. [Dose-effect relationship of traditional Chinese medicine formula for promoting blood circulation to remove stasis on ADP-induced platelet aggregation and rabbit plasma thrombin time].

    PubMed

    Zhang, Yanhua; Tang, Yuping; Guo, Jianming; Ding, Anwei; Duan, Jinao

    2009-11-01

    To investigate the effect of five traditional Chinese medicine formula for promoting blood circulation to remove stasis (Xuefuzhuyu Tang, Shaofuzhuyu Tang, Gexiazhuyu Tang, ShentongZhuyu Tang, Tongqiaohuoxue Tang) on platelet aggregation and clotting time in a dose-response relationship. The platelet aggregation was tested with Born's method and thrombin time (TT) method was established to determine the clotting time. The formula for promoting blood circulation to remove stasis showed significant inhibitory effects on the platelet aggregation and prolonged clotting time, the supernate of 80% alcohol solution showed the most potent inhibitory activity among the three kinds of samples from one formula (P < 0.01), especially the supernate of Shaofuzhuyu Tang and Gexiazhuyu Tang were better than other formula on platelet aggregation. About the anticoagulant, the whole formula showed the evidently prolonging the clotting time than other two fractions (P < 0.01) and the precipitation were the worst. The formula for promoting blood circulation to remove stasis showed significant effect on platelet aggregation and clotting time, and different samples of the formula had different efficacy. The study established a foundation for further bio-activity evaluation of these formulae and provided evidence for the treatment of cardiovascular and cerebrovascular diseases.

  19. Clinical observations on 100 cases of ulcerative colitis treated with the method of clearing away heat, expelling dampness, promoting blood circulation and healing ulcer.

    PubMed

    Ye, Bai; Shen, Hong; Lu, Yue; Wang, Ya-qi

    2010-06-01

    To observe the clinical therapeutic effect of the method of clearing away heat, expelling dampness, promoting blood circulation and healing ulcer on ulcerative colitis. The 100 cases were randomly divided into a control group of 45 cases treated with retention enema of the enterosoluble tablet sulfasalazine once every evening and a treatment group of 55 cases treated with retention enema of the decoction for clearing away heat, expelling dampness, promoting blood circulation and healing ulcer once every evening. The patients in both groups orally took Chinese drug for basic treatment for 30 days as a course. After treatment, the clinical therapeutic effects in the 2 groups were compared and changed symptoms in intestinal mucosa were observed under endoscope. The total effective rate of treatment group was better in relieving symptoms of TCM syndrome (90.9%) and intestinal mucosa (83.3%) than that of control group (68.9%, 56.3%) (P<0.01 or P<0.05). With good therapeutic effect on ulcerative colitis, Qinghua Huoxue Lianyang therapy (clearing away heat, expelling dampness, promoting blood circulation and healing ulcer) can obviously repair intestinal mucosa.

  20. [Controlled clinical trials of therapeutic effects of Chinese herbs promoting blood circulation and removing blood stasis on the treatment of reflex sympathetic dystrophy with type of stagnation of vital energy and blood stasis].

    PubMed

    Xu, Rui-Sheng; Zong, Xu-Hua; Li, Xiao-Gang

    2009-12-01

    To observe clinical results of Chinese herbs promoting blood circulation and removing blood stasis on the treatment of reflex sympathetic dystrophy (RSD) with type of stagnation of vital energy and blood stasis. RSD with type of stagnation of vital energy and blood stasis was distinguished as erubescence, high temperature, perspiration, damp and acro-edema, with middle level pain. From 2006 to 2008, 58 patients with RSD of stagnation of vital energy and blood stasis were randomly divided into the treatment group (30 cases) and the control group (28 cases). The former were treated with Chinese medicine to activate blood circulation and improve bone and muscle nourishment. Chinese medicine includes: Caesalpinia Sappan 10 g, Ligusticum Chuanxiong 6 g, Frankincense 6 g, Angelica 10 g, Safflower 6 g, Myrrh 6 g, Ground Beetle 10 g, Araliaceae 3 g, Radix Paeoniae Rubra 10 g, Pericarpium Citri Reticulatae 5 g, Lawn Pennywort Herb 15 g, Manis Pentadactyla 10 g, Corydalis Yanhusuo 10 g, Rhizoma Drynariae 15 g, which were boiled into decoction and the patients were take orally everyday with a course of treatment for 10 days, together with the boiled Chinese traditional medicine of stretching muscle and activating blood circulation to fume and wash the limbs twice everyday. The compatibility of medicines in prescription includes: Lycopodium Japanicum Grass 10 g, Gentiana Macrophylla Pall 10 g, Radix Angelicae Pubescentis 10 g, Angelica 10 g, Uncaria 10 g, Frankincense 6 g, Myrrh 6 g, Safflower 6 g. Control group were treated with a placebo of the same color for oral use and external application. The delivery times, method and the time of therapy were all the same as the treatment group. After 30 days' treatment, the effective indexes of VAS pain score and swelling condition were observed in both groups. VAS pain score: the treatment group decreased (3.8 +/- 0.8) points and the control group decreased (1.0 +/- 0.3) points, the difference between the two groups was significantly

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

    PubMed

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

    2014-12-01

    Peanut agglutinin (PNA), which accounts for ~0.15% of the weight of the common peanut, is a carbohydrate-binding protein that binds the oncofoetal Thomsen-Friedenreich (TF) disaccharide (galactoseβ1,3N-acetylgalactosamineα-) that is overexpressed by ~90% of human cancers. Previous studies have shown that PNA is highly resistant to cooking and digestion and rapidly enters the human blood circulation after peanut ingestion. This study investigates the hypothesis that PNA appearance in the circulation after peanut ingestion may mimic the actions of endogenous TF-binding human galectin-3 in metastasis promotion. It shows that PNA at concentrations similar to those found in blood circulation after peanut ingestion increases cancer cell heterotypic adhesion to the blood vascular endothelium and enhances the formation of tumour cell homotypic aggregates, two important steps in the metastasis cascade, and enhances metastasis in a mouse metastasis model. These effects of PNA are shown to result from its interaction with the cancer-associated TF disaccharide on the transmembrane mucin protein MUC1, causing MUC1 cell surface polarization that reveals underlying cell surface adhesion molecules. Thus, PNA appearance in the blood circulation after peanut ingestion mimics the actions of endogenous galectin-3 and promotes cancer cell metastatic spread by interaction with cancer-associated TF/MUC1. As metastasis accounts for the majority of cancer-associated fatality, regular consumption of peanuts by cancer patients would therefore be expected to have an adverse effect on cancer survival. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Effects of extracts and isolated compounds from safflower on some index of promoting blood circulation and regulating menstruation.

    PubMed

    Yao, Dong; Wang, Zheng; Miao, Li; Wang, Linyan

    2016-09-15

    Carthamus tinctorius is used as one of the Traditional Chinese Medicine (TCM) materials in prescriptions and composite to promote blood circulation to remove blood stasis, regulate menstruation and alleviate pain for over 2500 years. Modern pharmacological experiments have demonstrated that safflower has wide-reaching biological activities, including dilating coronary artery, modulating immune system, improving myocardial ischemia, anticoagulation and thromboprophylaxis, antioxidation, antihypoxic, antiaging, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. Platelet aggregation of safflower extract and main constituents in safflower were determined by PAF-induced or ADP-induced platelet aggregation in vitro. Anticoagulation activity was measured by clotting assay of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) according to the methods provided by the biological reagents provider (Sun Biochemical). Antioxidant effects of safflower were assessed using DPPH radical-scavenging activity test, ABTS radical-scavenging activity test and ferric reducing antioxidant power test. In addition, rats ovary granulosa cell proliferation activity was used for the bio-activity index on regulate menstruation of safflower. Safflower extract at the concentration of 0.7g/mL (P<0.001) and 0.5g/mL (P<0.01) had significantly antagonistic effect on PAF-induced platelet aggregation, compared with negative control. And the anti-platelet aggregation of 0.7g/mL safflower extract was significantly stronger than that of positive control (P<0.001). 0.7g/mL of hydroxysafflor yellow A (P<0.01), anhydrosafflor yellow B (P<0.05), 6-hydroxykaempferol-3-O-rutinoside (P<0.05), keampferol-3-O-β-rutinoside (P<0.01) had significant effect on platelet aggregation compared with negative control. Safflower extract at the concentration of 0.5g/mL (P<0.001) and 0.125g/mL (P<0.01) could significantly inhibit ADP-induced platelet

  3. Blood circulation under weightless conditions

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

  4. [Effects of promoting blood circulation to remove meridian obstruction combined with medicinal guides on related osteogenesis factors in rabbits with femoral head necrosis].

    PubMed

    Wang, Rong-tian; Kong, Xiang-ying; Tian, Neng; Lin, Na; Chen, Wei-heng

    2013-07-01

    To observe effects of blood circulation promoting compounds combined with medicinal guides on content of bone glaprotein (BGP), bone morphogenetic protein-2 (BPM-2) and expression of BMP-2 mRNA in rabbits with femoral head necrosis, and explore its mechanism. Ninety-eight healthy Spragur-Dawley male rabbits were collected and weighted 2.2 to 2.8 kg. Eighty-four rabbits were built femoral head necrosis model by freezing left femoral head in liquid nitrogen, then randomly divided into 6 groups, 14 in each group. The 6 groups included model group,promoting blood circulation to remove meridian obstruction group,promoting blood circulation to remove meridian obstruction combined with achyranthes bidentata group,radix angelicae pubescentis, asarum group, and platycodon grandiflorum group,other 14 rabbits were sham operation group. While drug groups were administrated corresponding Chinese herb after molding,model group and shamp operation group were given saline. Recombinant human granulocyte-colony stimulating factor ( 30 microg x kg(-1) x d(-1))were injected into all rabbits for 7 days. Samples were taken on the second and fourth week,the content of BGP and BMP-2 were detected by enzyme-linked immunosorbent assay (ELSA) and radioimmunoassay (RIA), histopathological changes of left femoral head were observed by Hematoxylin and Eeosin staining (HE), and expression of BMP-2 mRNA were tested by fluorescence in situ hybridization. Compared with sham operation group, the rate of empty lacunae femoral head were obviously increased in model group, and the content of BGP were increased on the second week, and BMP-2 and BMP-2 mRNA were decreased on the fourth week. Compared with model group, the content of BGP, BMP-2 and BMP-2 mRNA were higher both of the second and fourth week in promoting blood circulation to remove meridian obstruction group. The rate of empty la- cunae femoral head were lower in achyranthes bidentata group, BGP, BMP-2 and BMP-2 mRNA were higher on the fourth

  5. [Experimental study on two-way application of drugs with neutral property for promoting blood circulation and removing blood stasis on cold and heat blood stasis syndromes II].

    PubMed

    Hao, Er-Wei; Deng, Jia-Gang; Du, Zheng-Cai; Zheng, Zuo-Wen; Yang, Ke; Wang, Qin; Tang, Yun-Li; Bao, Chuan-Hong; Lu, Xiao-Yan; Tang, Zhi-Ling; Deng, Xiu-Qiong

    2013-02-01

    To further study the characteristics of drugs with neutral property in two-way application and conditioned dominance by observing the action characteristic of 10 traditional Chinese medicines with neutral property in hemorheological indicators of heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome rats. The model of heat stagnation and blood stasis syndrome rats was established by injecting carrageenan and dry yeast, while the model of cold stagnation and blood stasis syndrome rats was established by body freezing. Subsequently, 10 traditional Chinese medicines with neutral property, 5 traditional Chinese medicines with heat property and 5 traditional Chinese medicines with cold property were selected for intervention to observe the changes in such indicators as whole blood viscosity, plasma viscosity and hematocrit and analyze the action characteristics of drugs with neutral property. ANOVA showed that among six of the 10 traditional Chinese medicines with neutral property, including Typhae Pollen, Sarcandrae Herba and Sappan lignum, could obviously increase the hemorheological indicators of both heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome rats; five traditional Chinese medicines with cold property, such as Salviae Miltiorrhizae Radix et Rhizoma, Leonuri Herba, Rhei Radix et Rhizoma, could significantly ameliorate the hemorheological indicators of heat stagnation and blood stasis syndrome rats (P < 0.01 or P < 0.05), and Salvia Miltiorrhiza Radix et Rhizoma alone could ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats (P < 0.05); all of the five traditional Chinese medicines with heat property could significantly ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats (P < 0.01), among which Carthami Flos and Notoginseng Radix et Rhizoma could significantly ameliorate the hemorheological indicators of cold

  6. Blood storage affects the detection of cellular prion protein on peripheral blood leukocytes and circulating dendritic cells in part by promoting platelet satellitism.

    PubMed

    Glier, Hana; Holada, Karel

    2012-06-29

    Flow cytometry represents an attractive approach for developing currently unavailable screening tests for prion diseases. Several studies have reported significant differences in the binding of antibodies directed against cellular prion protein (PrP(C)) to blood cells of prion-infected subjects compared with healthy controls. However, flow cytometry data usually show large individual variations in detected PrP(C) levels in both infected and control groups, rendering the interpretation of individual patient data difficult. To determine how pre-analytical variables, such as the choice of anticoagulant, whether or not the blood was stored, and the storage temperature, affect the detection of PrP(C) in blood cells. Blood from healthy donors was collected in EDTA or citrate anticoagulant and processed either immediately or after storage overnight at room temperature or at 4°C. The expression of PrP(C) by T cells, B cells, NK cells, monocytes and circulating dendritic cells was evaluated using quantitative flow cytometry with the PrP(C) monoclonal antibodies AG4 and AH6. The anticoagulation of blood with citrate resulted in decreased levels of PrP(C) on monocytes but not the other cell types. The storage of blood prior to analysis led to a significant decrease in the levels of PrP(C) on the cells studied, although there were substantial differences between the cell populations. This decrease was more pronounced when using mAb AG4, which targets the N-terminal portion of the PrP(C) molecule, or following storage at room temperature. Moreover, we identified platelet satellitism on leukocytes, especially on monocytes and granulocytes, as an additional factor contributing to the heterogeneity of PrP(C) detection in stored blood. Our study demonstrates that the storage of blood prior to analysis greatly affects the detection of PrP(C) by flow cytometry. To limit the inclusion of storage-generated artifacts, we recommend the processing of blood samples immediately after their

  7. [Experimental study on two-way application of traditional Chinese medicines capable of promoting blood circulation and removing blood stasis with neutral property in cold and hot blood stasis syndrome I].

    PubMed

    Hao, Er-Wei; Deng, Jia-Gang; Du, Zheng-Cai; Yan, Ke; Zheng, Zuo-Wen; Wang, Qin; Huang, Li-Zhen; Bao, Chuan-Hong; Deng, Xiu-Qiong; Lu, Xiao-Yan; Tang, Zhi-Ling

    2012-11-01

    To study the action characteristics of "two-way application and conditioned dominance" of traditional Chinese medicines with neutral property by observing the action characteristic of 10 traditional Chinese medicines capable of promoting blood circulation and removing blood stasis with neutral property in the microcirculation in rats with heat stagnation and blood stasis syndrome. The rat model with heat stagnation and blood stasis syndrome was established by injecting carrageenan and dry yeast, and the rat model with cold stagnation and blood stasis syndrome was built by the body freezing method. Ten traditional Chinese medicines with neutral property, including 5 with hot property and 5 with cold property, were selected for intervention to observe blood flow rate and flow state indicators in rat auricles and make a comparative analysis on action characteristics of traditional Chinese medicines with neutral property. ANOVA showed that among the 10 traditional Chinese medicines with neutral property, 6 such as Typhae Pollen, Sappan Lignum and Vaccariae Semen can obviously increase the blood flow rate (P < 0.01 or P < 0.05) in the above two models; all of the 5 traditional Chinese medicines with cold property can increase the blood flow rate (P < 0.01 or P < 0.05) in the rat model with heat stagnation and blood stasis syndrome, but only Salvia miltiorrhiza can increase the blood flow rate (P < 0.01 or P < 0.05) in the rat models with cold stagnation and blood stasis syndrome, while other medicines showed no notable effect; among the 5 traditional Chinese medicines with hot property, Carthamus tinctorius and Ligusticum chuanxiong can increase the blood flow rate (P < 0.01 or P < 0.05) in the rat models with cold stagnation and blood stasis syndrome, but had no obvious effect to the blood flow rate in the rat models with heat stagnation and blood stasis syndrome. According to the analysis on average blood flow rate, traditional Chinese medicines with natural and cold

  8. 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.

  9. 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

  10. [Effect of 5 warm-hot nature Chinese drugs for promoting blood circulation and removing blood stasis on 5-HT, NE, and endocrine hormones of rats of cold coagulation and blood stasis syndrome].

    PubMed

    Wang, Peng; Fu, Xian-Jun; Zhou, Yang; Wang, Zhen-Guo

    2014-11-01

    To study the mechanism of warm-hot nature Chinese drugs (WHNCD) for promoting blood circulation and removing blood stasis (PBCRBS) for intervening model rats of cold coagulation and blood stasis syndrome (CCBSS). CCBSS rat model was set up in outbred SD rats using ice water immersion method. Totally 300 successfully modeled CCBSS rats were randomly divided into 5 groups according to the principle of balance weight, 60 in each group. Contents of triothyrone (T3), tetraiodothyroine (T4), progesterone (P), 5-hydroxytryptamine (5-HT), and noradrenalin (NE) were paralleledly detected in all groups. Then rats in each group were subdivided into 6 subgroups as the model group, the curcuma group, the Ligsticum Chuanxiong group, the safflower group, the Rhizoma Corydalis group, and the Olibanumg group. Besides, 5 normal control groups were set up for 5 indices, 50 rats in total. We need 70 rats (7 groups) to finish observing 1 index, 350 rats in total for 5 indices. Except those in the model group and the normal control group, rats were administered with corresponding decoction at 20 g crude drugs/kg body weight by gastrogavage, 3 mL each time, once daily for 7 successive days. Equal volume of normal saline was given to rats in the normal control group and the model group. Contents of T3, T4, P, 5-HT, and NE were detected before treatment and 1 week after treatment. Compared with before treatment in the same group, T3 increased in the Ligsticum Chuanxiong group and the Olibanumg group, 5-HT increased in the Ligsticum Chuanxiong group, T4, NE, and P increased in all medicated groups (P < 0.05). Compared with the normal control group, contents of T3, T4, 5-HT, NE, and P in the model group decreased (P < 0.05). Compared with the model group, contents of T3, T4, 5-HT, and NE increased in each medicated group (P < 0.05). There was statistical difference in contents of P between the Ligsticum Chuanxiong group and the Olibanumg group (P < 0.05). WHNCD for PBCRBS had regulatory

  11. Inhibition of PAI-1 Activity by Toddalolactone as a Mechanism for Promoting Blood Circulation and Removing Stasis by Chinese Herb Zanthoxylum nitidum var. tomentosum.

    PubMed

    Yu, Bo; Zhang, Guangping; Jin, Lingling; Zhang, Bo; Yan, Dong; Yang, Hong; Ye, Zuguang; Ma, Tonghui

    2017-01-01

    Traditional Chinese medicine has been used to treat a variety of human diseases for many centuries. Zanthoxylum nitidum var. tomentosum is used as an adjuvant to promote blood circulation and remove stasis. However, the mechanisms of improving circulation and other biological activities of Z. nitidum var. tomentosum are still unclear. Plasminogen activator inhibitor-1 (PAI-1) regulates the plasminogen activation system through inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA). PAI-1 has been linked to fibrin deposition that evolves into organ fibrosis and atherosclerosis. In the present study, we showed that ethanol extract prepared from Z. nitidum var. tomentosum exhibited PAI-1 inhibitory activity, and identified toddalolactone as the main active component that inhibited the activity of recombinant human PAI-1 with IC50 value of 37.31 ± 3.23 μM, as determined by chromogenic assay, and the effect was further confirmed by clot lysis assay. In vitro study showed that toddalolactone inhibited the binding between PAI-1 and uPA, and therefore prevented the formation of the PAI-1/uPA complex. Intraperitoneal injection of toddalolactone in mice significantly prolonged tail bleeding and reduced arterial thrombus weight in a FeCl3-induced thrombosis model. In addition, the hydroxyproline level in the plasma and the degree of liver fibrosis in mice were decreased after intraperitoneal injection of toddalolactone in CCl4-induced mouse liver fibrosis model. Taken together, PAI-1 inhibition exerted by toddalolactone may represent a novel molecular mechanism by which Z. nitidum var. tomentosum manifests its effect in the treatment of thrombosis and fibrosis.

  12. Inhibition of PAI-1 Activity by Toddalolactone as a Mechanism for Promoting Blood Circulation and Removing Stasis by Chinese Herb Zanthoxylum nitidum var. tomentosum

    PubMed Central

    Yu, Bo; Zhang, Guangping; Jin, Lingling; Zhang, Bo; Yan, Dong; Yang, Hong; Ye, Zuguang; Ma, Tonghui

    2017-01-01

    Traditional Chinese medicine has been used to treat a variety of human diseases for many centuries. Zanthoxylum nitidum var. tomentosum is used as an adjuvant to promote blood circulation and remove stasis. However, the mechanisms of improving circulation and other biological activities of Z. nitidum var. tomentosum are still unclear. Plasminogen activator inhibitor-1 (PAI-1) regulates the plasminogen activation system through inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA). PAI-1 has been linked to fibrin deposition that evolves into organ fibrosis and atherosclerosis. In the present study, we showed that ethanol extract prepared from Z. nitidum var. tomentosum exhibited PAI-1 inhibitory activity, and identified toddalolactone as the main active component that inhibited the activity of recombinant human PAI-1 with IC50 value of 37.31 ± 3.23 μM, as determined by chromogenic assay, and the effect was further confirmed by clot lysis assay. In vitro study showed that toddalolactone inhibited the binding between PAI-1 and uPA, and therefore prevented the formation of the PAI-1/uPA complex. Intraperitoneal injection of toddalolactone in mice significantly prolonged tail bleeding and reduced arterial thrombus weight in a FeCl3-induced thrombosis model. In addition, the hydroxyproline level in the plasma and the degree of liver fibrosis in mice were decreased after intraperitoneal injection of toddalolactone in CCl4-induced mouse liver fibrosis model. Taken together, PAI-1 inhibition exerted by toddalolactone may represent a novel molecular mechanism by which Z. nitidum var. tomentosum manifests its effect in the treatment of thrombosis and fibrosis. PMID:28785222

  13. 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.

  14. 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.

  15. Acute strength training promotes responses in whole blood circulating levels of miR-146a among older adults with type 2 diabetes mellitus.

    PubMed

    Morais Junior, Gilberto Santos; Souza, Vinicius Carolino; Machado-Silva, Wilcelly; Henriques, Adriane Dallanora; Melo Alves, Andressa; Barbosa Morais, Danilo; Nóbrega, Otávio Toledo; Brito, Ciro José; Dos Santos Silva, Roberto Jerônimo

    2017-01-01

    Type 2 diabetes mellitus (T2DM) consists of a set of metabolic and endocrine disorders which evolve into deficiency in insulin action and hyperglycemia. Physical exercise is considered the main intervention to prevent and control T2DM. Literature has suggested that circulating microRNAs (miRs) help to understand responses to physical activity among diabetic patients. Thus, the aim of this study was to analyze the acute effect of two interventions (strength and cardiovascular) on the total, whole blood circulating concentrations of miR-126, miR-146a and miR-155 in older adults with and without T2DM. A total of 23 male and female older adults (68.2±5.3 years) participated in the trial, 13 of whom presented with controlled T2DM and 10 were nondiabetics. They underwent both interventions separately, performed with intensity from 60% to 70% of reserve heart rate. Glucose and miRs levels were quantified and compared across groups with baseline titers as covariables. Diabetic patients showed more reduction in serum blood glucose than nondiabetics, with a great magnitude of reduction after the strength training intervention, which was paralleled by a positive change of the whole blood circulating levels of miR-146a, but not of the other miRs. Our report supports evidence that miR-146a levels in peripheral blood leukocytes are negatively associated with a state of insulin resistance, which is suggested as a novel marker to trace response to antidiabetic interventions.

  16. 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

    Qin, Wenmin; Zhao, Kai; Yang, Haiyan

    2016-11-01

    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

  17. 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

  18. Chinese patent medicine for chronic obstructive pulmonary disease based on principles of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm: a systematic review of randomized controlled trials.

    PubMed

    Liu, Wei; Yang, Shuang; Fu, Min; Li, Jian; Song, Yaling; Wei, Baolin; Liu, Enshun; Sun, Zengtao

    2015-02-01

    To assess the efficacy and safety of Chinese patent medicine (CPM) with the principle of tonifying Qi, promoting blood circulation by removing blood stasis, and resolving phlegm (TQ-PBC-RP) in the management of stable chronic obstructive pulmonary disease (COPD). A systematic review of randomized controlled trials (RCTs) identified from electronic databases and print was conducted. RCTs testing CPMs with TQ-PBC-RP against any type of controlled intervention in patients with stable COPD and assessing clinically relevant outcomes were included. Methodological quality was evaluated with the risk of bias tool according to systematic review handbook 5.0.2. Quality of evidence was estimated by the rating approach developed by the Grading of Recommendations, Assessment, Development, and Evaluation Working Group. Thirteen eligible RCTs with 12 oral CPMs were tested. Significant differences between groups in favor of CPMs were not reported in all trials. Most trials included were deemed to be of low methodological quality with poor evidence quality. Because of large data heterogeneity, statistical pooling was not performed for all outcomes. The effectiveness of CPM in the treatment of stable COPD is not supported by evidence. Currently, evidence from RCTs is scarce and methodologically weak. Considering the popularity of CPMs among patients undergoing COPD, rigorously designed trials are warranted.

  19. [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.

  20. Portal Venous Blood Circulation Supports Immunosuppressive Environment and Pancreatic Cancer Circulating Tumor Cell Activation.

    PubMed

    Arnoletti, Juan Pablo; Zhu, Xiang; Almodovar, Alvin J O; Veldhuis, Paula P; Sause, Ryan; Griffith, Elizabeth; Corpus, George; Chang, Jeffrey C C; Fanaian, Naʼim; Litherland, Sally A

    2017-01-01

    Aggressive spread and liver metastases are predominant features of pancreatic ductal adenocarcinoma (PDAC). This study investigates activation of PDAC circulating tumor cells (CTC) and immunosuppression in the portal venous system. Portal venous and peripheral blood were collected during pancreaticoduodenectomy from patients with PDAC (n = 21) or other non-PDAC pancreatic conditions (n = 20). Circulating tumor cells were isolated by fluorescence-activated cell sorting and characterized for messenger RNA (mRNA) expression and acetylated chromatin encoding K-RAS exon 12 mutation (K-RASmut). Myeloid-derived suppressor cells (MDSC) were identified using flow cytometry. Pancreatic ductal adenocarcinoma K-RASmut mRNA expression in portal venous blood CTC was significantly elevated compared with preoperative and postoperative peripheral blood (P = 0.0123 and P = 0.0246, respectively). There was no significant variation in total CTC numbers between portal and peripheral blood.Portal venous M-MDSC were elevated compared with peripheral blood in PDAC patients (P = 0.0065). M-MDSC increases correlated with K-RASmut mRNA-expressing CTC present in PDAC portal blood (P < 0.0001). Association of MDSC with active CTC in portal venous blood may support immunosuppression within the portal venous circulation to promote PDAC CTC survival.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. [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.

  6. 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.

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

    PubMed

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

    2010-06-22

    The primitive blood circulation requires intravascular plasma flow. However, it remains unclear whether the onset of earliest blood circulation is dependent solely on establishment of a functional circulatory organ or whether it also requires active processes inherent in blood cells. In this study, we present novel mechanisms for the onset of blood circulation by monitoring fluorescently labeled blood precursors and blood vessels in zebrafish. The earliest blood circulation occurs synchronously. This synchrony is achieved by the retention of erythroid precursors on the lumen of the vasculature after their invasion from the subaortic region, and then by simultaneous release of these precursors into the flow. Morphological and biochemical analyses suggest that the onset of blood circulation accompanies disruption of blood cell-to-vessel adhesion and requires metalloprotease-dependent processes. ADAM8, a member of the a disintegrin and metalloprotease (ADAM) family, mediates the onset of blood circulation. In ADAM8-depleted embryos, erythroid cells fail to detach from the vascular lumen and stagnate. Expression of a protease-defective ADAM8 in erythroid cells causes dominant-negative effects on blood circulation, suggesting cell-autonomous roles of ADAM8. Based on these findings, we propose that the first erythroid cells require both flow-dependent passive and proteolysis-dependent active processes to enter the circulation. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. 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…

  9. 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…

  10. 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.

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

    PubMed

    Remizova, M I; Gerbut, K A

    2014-05-01

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

  12. Mechanisms of Qi-blood circulation and Qi deficiency syndrome in view of blood and interstitial fluid circulation.

    PubMed

    Yao, Wei; Yang, Hongwei; Ding, Guanghong

    2013-08-01

    Based on comparison between fundamental theories of Traditional Chinese Medicine (TCM) and Western Medicine (WM) and modern scientific research on meridians, we find that "Qi" in TCM is closely related to tissue fluid. In this study, the essence of Qi is explored in the view of circulation of blood and interstitial fluid. Because the concept of Qi is complicated, Qi deficiency syndrome (QDS) is chosen to probe the relationship between of Qi deficiency and Qi-blood circulation (QBC). We analyze Qi-blood theory in terms of WM, set up a hemodynamic model to describe QBC, and review clinical research on QDS in the view of blood-interstitial fluid circulation. QDS is caused by imbalances of substance exchanges between blood and interstitial fluid, leading to an increase in the interstitial liquid volume or a decrease and retention of metabolic wastes in interstitial fluid. This study describes the essence of Qi, providing support for further research on theories of Qiand Qi-blood circulation in TCM.

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

    PubMed

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

    2014-10-01

    Multifunctional polymers with defined structure and biocompatibility are critical to the development of drug delivery systems and bioconjugates. In this article, the synthesis, in vitro blood compatibility, cell viability, in vivo circulation, biodistribution, and clearance of hybrid copolymers based on linear and branched polyglycerol are reported. Hybrid polyglycerols (M(n) ≈ 100 kDa) are synthesized with different compositions (15-80 mol% linear polyglycerol). Relatively small hydrodynamic size and radius of gyration of the hybrid polyglycerols suggest that they are highly compact functional nanostructures. The hybrid polyglycerols show excellent blood compatibility as determined by measuring their effects on blood coagulation, red blood cell aggregation, hemolysis, platelet, and complement activation. The cell viability in presence of hybrid polyglycerols is excellent up to 10 mg mL(-1) concentration and is similar to both dextran and polyvinyl alcohol. Furthermore, tritium labeled hybrid polyglycerol shows long blood circulation (t(1/2β)= 34 h) with minimal organ accumulation in mice. Multifunctionality, compact nature, biocompatibility, and the long blood circulation make these polymers attractive for the development of bioconjugates and drug delivery systems. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. [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.

  15. 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

  16. 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

  17. Is hydrogen sulfide a circulating "gasotransmitter" in vertebrate blood?

    PubMed

    Olson, Kenneth R

    2009-07-01

    Hydrogen sulfide (H(2)S) is gaining acceptance as a signaling molecule and has been shown to elicit a variety of biological effects at concentrations between 10 and 1000 micromol/l. Dissolved H(2)S is a weak acid in equilibrium with HS(-) and S(2-) and under physiological conditions these species, collectively referred to as sulfide, exist in the approximate ratio of 20% H(2)S, 80% HS(-) and 0% S(2-). Numerous analyses over the past 8 years have reported plasma or blood sulfide concentrations also in this range, typically between 30 and 300 micromol/l, thus supporting the biological studies. However, there is some question whether or not these concentrations are physiological. First, many of these values have been obtained from indirect methods using relatively harsh chemical conditions. Second, most studies conducted prior to 2000 failed to find blood sulfide in micromolar concentrations while others showed that radiolabeled (35)S-sulfide is rapidly removed from blood and that mammals have a relatively high capacity to metabolize exogenously administered sulfide. Very recent studies using H(2)S gas-sensing electrodes to directly measure sulfide in plasma or blood, or HPLC analysis of head-space gas, have also indicated that sulfide does not circulate at micromolar levels and is rapidly consumed by blood or tissues. Third, micromolar concentrations of sulfide in blood or exhaled air should be, but are not, malodorous. Fourth, estimates of dietary sulfur necessary to sustain micromolar levels of plasma sulfide greatly exceed the daily intake. Collectively, these studies imply that many of the biological effects of sulfide are only achieved at supra-physiological concentrations and they question whether circulating sulfide is a physiologically relevant signaling molecule. This review examines the blood/plasma sulfide measurements that have been reported over the past 30 years from the perspective of the analytical methods used and the potential sources of error.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. [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.

  4. 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'…

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

    PubMed Central

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

    2016-01-01

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

  6. 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.

  7. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA.

    PubMed

    Haber, Daniel A; Velculescu, Victor E

    2014-06-01

    The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell-derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments. Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis. ©2014 American Association for Cancer Research.

  8. Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA

    PubMed Central

    Haber, Daniel A.; Velculescu, Victor E.

    2015-01-01

    The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell–derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments. Significance Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis. PMID:24801577

  9. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  14. 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.

  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. [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.

  17. [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

  18. 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

  19. Circulating galectins -2, -4 and -8 in cancer patients make important contributions to the increased circulation of several cytokines and chemokines that promote angiogenesis and metastasis.

    PubMed

    Chen, C; Duckworth, C A; Fu, B; Pritchard, D M; Rhodes, J M; Yu, L-G

    2014-02-04

    Circulating concentrations of the cytokines interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and chemokines monocyte chemotatic protein 1 (MCP-1)/CCL2 and growth-regulator oncogene α (GROα)/chemokine C-X-C motif ligand 1 are commonly increased in cancer patients and they are increasingly recognised as important promoters, via divergent mechanisms, of cancer progression and metastasis. The effect of galectins-2, -4 and -8, whose circulating levels are highly increased in cancer patients, on endothelial secretion of cytokines was assessed in vitro by cytokine array and in mice. The relationship between serum levels of galectins and cytokines was analysed in colon and breast cancer patients. Galectins-2, -4 and -8 at pathological concentrations induce secretion of G-CSF, IL-6, MCP-1 and GROα from the blood vascular endothelial cells in vitro and in mice. Multiple regression analysis indicates that increased circulation of these galectins accounts for 41∼83% of the variance of these cytokines in the sera of colon and breast cancer patients. The galectin-induced secretion of these cytokines/chemokines is shown to enhance the expression of endothelial cell surface adhesion molecules, causing increased cancer-endothelial adhesion and increased endothelial tubule formation. The increased circulation of galectins -2, -4 and -8 in cancer patients contributes substantially to the increased circulation of G-CSF, IL-6 and MCP-1 by interaction with the blood vascular endothelium. These cytokines and chemokines in turn enhance endothelial cell activities in angiogenesis and metastasis.

  20. [Effect of activating blood circulation or activating blood circulation and detoxication on platelet activation, inflammation, and coagulation status in acute myocardial infarction rats].

    PubMed

    Ma, Xiao-Juan; Guo, Chun-Yu; Yin, Hui-Jun; Liu, Yue; Shi, Da-Zhuo

    2014-11-01

    To observe the effect of activating blood circulation drugs or activating blood circulation and detoxication drugs on indices of platelet activation, inflammation, and coagulation status correlated with blood-stasis and toxin in acute myocardial infarction rats. Totally 100 male SD rats were randomly divided into the sham-operation group, the model group, the activating blood circulation group, the activating blood circulation and detoxication group, and the metoprolol group, 20 in each group. Rats in the activating blood circulation group were administered with Xiongshao Capsule at the daily dose of 0.39 g/kg. Rats in the activating blood circulation and detoxication group were administered with Xiongshao Capsule (at the daily dose of 0.39 g/kg) and Huanglian Capsule (at the daily dose of 0.135 g/kg). Rats in the metoprolol group received metoprolol at the daily dose of 2.25 mg/kg. And rats in the rest two groups were administered with normal saline. All medication lasted for 3 successive weeks. After the last administration, the rat model of acute myocardial infarction was prepared by ligation of left anterior descending artery. No ligation was given to rats in the sham-operation group. Animals were sacrificed 24 h after modeling. Tumor necrosis factor-α (TNF-α), β-thromboglobulin (β-TG), platelet α granule membrane protein-140 (GMP-140), 11 dehydro-thromboxane B2 (11-DH-TXB2), fibrinopeptide A (FPA), antithrombin III (AT-III), and D-dimer (DD) were detected by ELISA. The mRNA expression of TNF-α was tested by RT-PCR. Platelet activation parameters were significantly increased in the model group, when compared with the sham-operation group (P < 0.01). Compared with the model group, all indices (except GMP-140 in the metoprolol group) obviously decreased in each medicated group (P < 0.01, P < 0.05). Besides, β-TG and 11-DH-TXB2 were superior in the activating blood circulation and detoxication group to that of the metoprolol group (P < 0.05). But 11-DH-TXB2

  1. Capture and Release of Viable Circulating Tumor Cells from Blood.

    PubMed

    Rawal, Siddarth; Ao, Zheng; Agarwal, Ashutosh

    2016-10-28

    We demonstrate a method for size based capture of viable circulating tumor cell (CTC) from whole blood, along with the release of these cells from chip for downstream analysis and/or culture. The strategy employs the use of a novel Parylene C membrane slot pore microfilter to capture CTC and a coating of poly (N-iso-propylacrylamide) (PIPAAm) for thermoresponsive viable release of the captured CTC. The capture of live cells is enabled by leveraging the design of a slot pore geometry with specific dimensions to reduce the shear stress typically associated with the filtration process. While the microfilter exhibits a high capture efficiency, the release of these cells is non-trivial. Typically, only a small percentage of cells are released when techniques such as reverse flow or cell scraping are used. The strong adhesion of these epithelial cancer cells to the Parylene C membrane is attributable to non-specific electrostatic interaction. To counteract this effect, we employed the use of PIPAAm coating and exploited its thermal responsive interfacial properties to release the cells from the filter. Blood is first filtered at room temperature. Below 32 °C, PIPAAm is hydrophilic. Thereafter, the filter is placed in either culture media or a buffer maintained at 37 °C, which results in the PIPAAm turning hydrophobic, and subsequently releasing the electrostatically bound cells.

  2. [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.

  3. 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.

  4. Experimental study of physiological advantages of assist circulation using oscillated blood flow.

    PubMed

    Kobayashi, S; Nitta, S; Yambe, T; Naganuma, S; Hashimoto, H; Fukuju, T; Tabayashi, K

    1995-07-01

    To estimate the effect of oscillated blood flow on hemodynamics in an awake condition, left ventricular assist circulation using oscillated blood flow was performed on 3 adult goats as chronic animal examination. A vibrating flow pump (VFP) was used for generating high-frequency oscillated flow. The blood flow rate of assisted circulation was approximately 1.0 L/min, and the driving frequency of VFP was 25 Hz. Systemic vascular resistance and arterial impedance were calculated in this study. Systemic vascular resistance during assist circulation was decreased compared with that without assistance. Oscillated blood flow may be effective in decreasing vascular resistance. Moreover, it was suggested from the study of arterial impedance that motive characteristics of the vascular wall against changing blood pressure may keep their normal reaction. Therefore, oscillated blood flow may be used for left ventricular assist circulation as concluded from the study of the characteristics of blood vessels.

  5. Prediction of Ocular Drug Distribution from Systemic Blood Circulation.

    PubMed

    Vellonen, Kati-Sisko; Soini, Esa-Matti; Del Amo, Eva M; Urtti, Arto

    2016-09-06

    Systemically circulating drugs may distribute to ocular tissues across the blood-ocular barriers. Ocular distribution is utilized in the treatment of ocular diseases with systemic medications, but ocular delivery of systemic drugs and xenobiotics may also lead to adverse ocular effects. Ocular distribution after systemic drug administration has not been predicted or modeled. In this study, distribution clearance between vitreous and plasma was obtained from a previous QSPR model for clearance of intravitreal drugs. These values were used in a pharmacokinetic simulation model to describe entry of unbound drug from plasma to vitreous. The simulation models predicted ocular distribution of 10 systemic drugs in rabbit eyes within 1.96 mean fold error and the distribution of cefepime from plasma to vitreous in humans. This is the first attempt to predict ocular distribution of systemic drugs. Reliable predictions were obtained using systemic concentrations of unbound drug, computational value of ocular distribution clearance, and a simple pharmacokinetic model. This approach can be used in drug discovery to estimate ocular drug exposure at an early stage.

  6. 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)

  7. 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

  8. 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.

  9. [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.

  10. Circulating galectins -2, -4 and -8 in cancer patients make important contributions to the increased circulation of several cytokines and chemokines that promote angiogenesis and metastasis

    PubMed Central

    Chen, C; Duckworth, C A; Fu, B; Pritchard, D M; Rhodes, J M; Yu, L-G

    2014-01-01

    Background: Circulating concentrations of the cytokines interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and chemokines monocyte chemotatic protein 1 (MCP-1)/CCL2 and growth-regulator oncogene α (GROα)/chemokine C-X-C motif ligand 1 are commonly increased in cancer patients and they are increasingly recognised as important promoters, via divergent mechanisms, of cancer progression and metastasis. Methods: The effect of galectins-2, -4 and -8, whose circulating levels are highly increased in cancer patients, on endothelial secretion of cytokines was assessed in vitro by cytokine array and in mice. The relationship between serum levels of galectins and cytokines was analysed in colon and breast cancer patients. Results: Galectins-2, -4 and -8 at pathological concentrations induce secretion of G-CSF, IL-6, MCP-1 and GROα from the blood vascular endothelial cells in vitro and in mice. Multiple regression analysis indicates that increased circulation of these galectins accounts for 41∼83% of the variance of these cytokines in the sera of colon and breast cancer patients. The galectin-induced secretion of these cytokines/chemokines is shown to enhance the expression of endothelial cell surface adhesion molecules, causing increased cancer-endothelial adhesion and increased endothelial tubule formation. Conclusion: The increased circulation of galectins -2, -4 and -8 in cancer patients contributes substantially to the increased circulation of G-CSF, IL-6 and MCP-1 by interaction with the blood vascular endothelium. These cytokines and chemokines in turn enhance endothelial cell activities in angiogenesis and metastasis. PMID:24384681

  11. The Clinical Utilization of Circulating Cell Free DNA (CCFDNA) in Blood of Cancer Patients

    PubMed Central

    Elshimali, Yahya I.; Khaddour, Husseina; Sarkissyan, Marianna; Wu, Yanyuan; Vadgama, Jaydutt V.

    2013-01-01

    Qualitative and quantitative testing of circulating cell free DNA (CCFDNA) can be applied for the management of malignant and benign neoplasms. Detecting circulating DNA in cancer patients may help develop a DNA profile for early stage diagnosis in malignancies. The technical issues of obtaining, using, and analyzing CCFDNA from blood will be discussed. PMID:24065096

  12. 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.

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

    PubMed

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

    2015-11-01

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

  14. Market Research and Magazine Circulation Promotion: A Case Study.

    ERIC Educational Resources Information Center

    Van Tubergen, G. Norman

    When a major national news magazine decided to advertise on television to increase circulation, market researchers had to design research procedures that would assess the effectiveness of various advertising options. The system was designed around the toll-free telephone number given in the advertisement, with the receiving operator recording the…

  15. 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.

  16. 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.

  17. [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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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

  4. Atmospheric circulation patterns which promote winter Arctic sea ice decline

    NASA Astrophysics Data System (ADS)

    Luo, Binhe; Luo, Dehai; Wu, Lixin; Zhong, Linhao; Simmonds, Ian

    2017-05-01

    The impact of winter atmospheric blocking over the Ural Mountains region (UB) coincident with different phases of the North Atlantic Oscillation (NAO) on the sea ice variability over the Barents and Kara Seas (BKS) in winter is investigated. It is found that the UB in conjunction with the positive phase of the NAO (NAO+) leads to the strongest sea ice decline. During this phase composites and trajectory analyses reveal an efficient moisture pathway to the BKS from the mid-latitude North Atlantic near the Gulf Stream Extension region where water vapor is abundant due to high sea surface temperatures. The NAO+-UB combination is an optimal circulation pattern that significantly increases the BKS water vapor that plays a major role in the BKS warming and sea ice reduction, while the increased sensible and latent heat fluxes play secondary roles. By contrast, much fewer dramatic impacts on the BKS are observed when the UB coincides with the neutral or negative phases of the NAO. Our results present new insights into the complex processes involved with Arctic sea ice reduction and warming. The mechanisms highlighted here potentially offer a perspective into the mechanisms behind Arctic multi-decadal climate variability.

  5. 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

  6. 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.

  7. Circulating blood cells function as a surveillance system for damaged tissue in Drosophila larvae

    PubMed Central

    Babcock, Daniel T.; Brock, Amanda R.; Fish, Greg S.; Wang, Yan; Perrin, Laurent; Krasnow, Mark A.; Galko, Michael J.

    2008-01-01

    Insects have an open circulatory system in which the heart pumps blood (hemolymph) into the body cavity, where it directly bathes the internal organs and epidermis. The blood contains free and tissue-bound immune cells that function in the inflammatory response. Here, we use live imaging of transgenic Drosophila larvae with fluorescently labeled blood cells (hemocytes) to investigate the circulatory dynamics of larval blood cells and their response to tissue injury. We find that, under normal conditions, the free cells rapidly circulate, whereas the tissue-bound cells are sessile. After epidermal wounding, tissue-bound cells around the wound site remain sessile and unresponsive, whereas circulating cells are rapidly recruited to the site of damage by adhesive capture. After capture, these cells distribute across the wound, appear phagocytically active, and are subsequently released back into circulation by the healing epidermis. The results demonstrate that circulating cells function as a surveillance system that monitors larval tissues for damage, and that adhesive capture, an important mechanism of recruitment of circulating cells to inflammatory sites in vertebrates, is shared by insects and vertebrates despite the vastly different architectures of their circulatory systems. PMID:18632567

  8. Correlation between blood circulation grading and angiogenesis using ultrasonic contrast of rabbit VX2 hepatic carcinoma.

    PubMed

    Xu, Chang-Song; Su, Yi-Jin; Xu, Ming; Liu, Wei; Hao, Peng; Du, Lian-Fang

    2016-02-01

    To build the rabbit model of VX2 hepatic carcinoma, examine the tumor body using the ultrasonic contrast and study the correlation between the blood circulation grading and angiogenesis. The VX2 tumor strain was prepared in the lateral muscle of the hind legs of 40 male New Zealand rabbits (which were purchased from Nanjing Senbao Biotech Co., Ltd.). The tumor block was embedded in the center of left liver lobe directly to build the rabbit model of VX2 hepatic carcinoma. The ultrasonic contrast was performed 14 d after implanting the tumor body. The semi-quantitative classification (0-IV level) was taken according to the blood flow of tumor vessel. Animals were executed using the air embolism method. The liver was separated to extract RNA and total protein respectively. The real-time PCR and western blotting method were employed to detect the expression of angiogenesis-related factors of VEGF, bFGF and TNF-α, while the ultrasonic contrast to detect the correlation with blood circulation grading. The Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables and analyze the correlation between the blood circulation grading and angiogenesis using the ultrasonic contrast. Thirty-three rabbits had the successful model of VX2 hepatic carcinoma. The blood circulation grading by ultrasonic contrast was: 2 cases at level 0 (6.60%), 5 cases at level I (16.7%), 12 cases at level II (40.0%), 6 cases at level III (20.0%) (local dense or clustered blood flow) and 5 cases at level IV (16.7%). The results showed that there was positive correlation between three angiogenesis-related factors and the blood circulation grading. The correlation coefficient between three angiogenesis-related factors and the blood circulation grading was over 0.9, which indicated the relatively high correlation. The ultrasound blood circulation grading for the hepatic carcinoma can clearly reflect the changes of blood vessel, which will be of

  9. [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.

  10. 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…

  11. 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…

  12. 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.

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

    PubMed

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

    2016-07-01

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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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…

  19. 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…

  20. [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.

  1. 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

  2. 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

  3. 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

  4. [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.

  5. 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

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

    PubMed Central

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

    2014-01-01

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

  7. [Suitable working conditions for elderly people with different degrees of compensation of dysfunctional blood circulation of eyes].

    PubMed

    Razumovskaya, A M; Razumovskiy, M I; Trofimova, S V

    2015-01-01

    In dealing with complex problems in labor and social rehabilitation of elderly people with different degrees of compensation of dysfunctional blood circulation of eyes, a great role play methods of rational and qualitative analysis of appropriate employment. The analysis of 110 patients of 55-70 years of age (220 eyes) with dysfunctional blood circulation of eyes has been done. Professional abilities of elderly patients with dysfunctional blood circulation of eyes depend on the state of functioning vision and the level of blood circulation of the eye. In our study we show the clinical and prognostic data and based on that we could develop the absolutely prohibited working conditions depending on the level dysfunctional blood circulation of eyes of elderly people.

  8. Citrullination of CXCL8 increases this chemokine's ability to mobilize neutrophils into the blood circulation.

    PubMed

    Loos, Tamara; Opdenakker, Ghislain; Van Damme, Jo; Proost, Paul

    2009-10-01

    During the first line defense of an infected host, circulating neutrophils invade the inflamed tissue, whereas mature neutrophils from the bone marrow pool migrate into the blood circulation and from there reinforce tissue infiltration. The CXC chemokine CXCL8, also know as interleukin-8, is a potent attractant of neutrophils. Recently, we discovered a new natural post-translational modification of CXCL8, i.e. the deimination of arginine into citrulline by peptidylarginine deiminases. The ability to provoke leukocytosis was assessed by intravenous administration of citrullinated CXCL8 in rabbits. Adsorption of citrullinated CXCL8 to the Duffy antigen/receptor for chemokines on human or rabbit erythrocytes was evaluated using a competitive binding assay. Finally, surface expression of adhesion molecules was studied after stimulating neutrophils with citrullinated CXCL8. Citrullination of CXCL8 significantly increased this chemokine's ability to recruit neutrophils into the blood circulation. In addition, the competitive binding properties of CXCL8 for the Duffy antigen/receptor for chemokines were impaired upon citrullination. Since the Duffy antigen/receptor for chemokines is an important scavenging receptor for CXCL8 in the blood stream, citrullination may delay CXCL8 clearance from the circulation. Furthermore, the shedding of CD62L (L-selectin) and the upregulation of CD11b (beta2-integrin) protein expression on CXCL8-induced neutrophils were improved by deimination of CXCL8, possibly contributing to the neutrophil egress from the bone marrow. Conversely, surface expression of CD15, the neutrophilic ligand of endothelial selectins, was equally well upregulated by intact and citrullinated CXCL8. These data show that citrullination of CXCL8 enhances leukocytosis, possibly through impaired chemokine clearance from the blood circulation and prolonged presentation to the bone marrow.

  9. 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

  10. Septin 9 promoter region methylation in free circulating DNA-potential role in noninvasive diagnosis of lung cancer: preliminary report.

    PubMed

    Powrózek, Tomasz; Krawczyk, Paweł; Kucharczyk, Tomasz; Milanowski, Janusz

    2014-04-01

    Currently, there are no sensitive diagnostic tests that could allow early detection of lung cancer. Among some cancer patients, epigenetic changes in the nature of methylation of different gene promoter regions are observed, which affect expression of suppressor genes such as septin 9 (SEPT9). Due to the ability of detecting these changes in free circulating DNA in peripheral blood, such genes may become ideal markers in early and noninvasive diagnostics of cancer. Methylation of SEPT9 promoter region in plasma DNA is observed frequently in colorectal cancer patients. The aim of the study was to define the frequency of SEPT9 promoter methylation in lung cancer patients and evaluation of usefulness of this marker in early diagnostic of lung cancer. Plasma samples were obtained from 70 untreated patients with different lung cancer pathological diagnosis and disease stage and from 100 healthy individuals. DNA was isolated from peripheral blood plasma and was then subjected to bisulfitation, purification and elution using Abbott mSEPT9 Detection Kit. Methylation level was assessed by real-time PCR with the use of specific SEPT9 promoter methylation probe. Each sample was assayed in the presence of positive and negative control. SEPT9 promoter methylation was detected in 31 (44.3% of the whole studied group) of lung cancer patients finding the result positive when methylation was detected in 1 out of 3 repetitions of each test sample determinations. The marker was present in patients with different pathological diagnosis and disease stage. Analysis of SEPT9 promoter region methylation may be useful in early diagnosis of lung cancer.

  11. 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.

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

    PubMed

    Datsyuk, O I

    2016-01-01

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

  13. 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

  14. Contributions of Respiration and Heartbeat to the Pulmonary Blood Flow in the Fontan Circulation.

    PubMed

    Honda, Takashi; Itatani, Keiichi; Takanashi, Manabu; Kitagawa, Atsushi; Ando, Hisashi; Kimura, Sumito; Nakahata, Yayoi; Oka, Norihiko; Miyaji, Kagami; Ishii, Masahiro

    2016-11-01

    In the Fontan circulation, driving forces with respiration, heartbeat, and lower limb muscle pump are relevant. However, the mechanics of these forces has not been proven, and their effects on the Fontan circulation remain unclear. We performed catheter examinations and measured pressure and flow velocity simultaneously in the bilateral pulmonary arteries of 12 Fontan patients 1 year after the operation. The pulmonary pressure and flow velocity data were decomposed into respiratory and heartbeat components by discrete Fourier analysis. We then calculated respiratory and cardiac wave intensity (WI) based on the respiratory and heartbeat components of pressure and flow velocity data. Respiratory WI formed 2 negative peaks, a backward expansion wave during the inspiratory phase, and then a backward compression wave during the expiratory phase. In 2 phrenic nerve palsy cases and 1 case of a patient on a respirator, respiratory WI showed disturbed patterns and a negative pattern, respectively. Cardiac WI showed 2 or 4 negative peaks, the time phase of which matched that of the atrial contractions. WI analysis elucidated that inspiration acts as a sucking driving force and increases the pulmonary blood flow in the Fontan circulation. Respiratory complications compromise efficiency in the Fontan circulation. It was also revealed that the pulmonary blood flow was mutually dammed up and sucked in by increases and decreases in atrial pressure. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Computational Prediction of Human Salivary Proteins from Blood Circulation and Application to Diagnostic Biomarker Identification

    PubMed Central

    Wang, Jiaxin; Liang, Yanchun; Wang, Yan; Cui, Juan; Liu, Ming; Du, Wei; Xu, Ying

    2013-01-01

    Proteins can move from blood circulation into salivary glands through active transportation, passive diffusion or ultrafiltration, some of which are then released into saliva and hence can potentially serve as biomarkers for diseases if accurately identified. We present a novel computational method for predicting salivary proteins that come from circulation. The basis for the prediction is a set of physiochemical and sequence features we found to be discerning between human proteins known to be movable from circulation to saliva and proteins deemed to be not in saliva. A classifier was trained based on these features using a support-vector machine to predict protein secretion into saliva. The classifier achieved 88.56% average recall and 90.76% average precision in 10-fold cross-validation on the training data, indicating that the selected features are informative. Considering the possibility that our negative training data may not be highly reliable (i.e., proteins predicted to be not in saliva), we have also trained a ranking method, aiming to rank the known salivary proteins from circulation as the highest among the proteins in the general background, based on the same features. This prediction capability can be used to predict potential biomarker proteins for specific human diseases when coupled with the information of differentially expressed proteins in diseased versus healthy control tissues and a prediction capability for blood-secretory proteins. Using such integrated information, we predicted 31 candidate biomarker proteins in saliva for breast cancer. PMID:24324552

  16. Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles

    PubMed Central

    Merkel, Timothy J.; Jones, Stephen W.; Herlihy, Kevin P.; Kersey, Farrell R.; Shields, Adam R.; Napier, Mary; Luft, J. Christopher; Wu, Huali; Zamboni, William C.; Wang, Andrew Z.; Bear, James E.; DeSimone, Joseph M.

    2011-01-01

    It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles. PMID:21220299

  17. Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles.

    PubMed

    Merkel, Timothy J; Jones, Stephen W; Herlihy, Kevin P; Kersey, Farrell R; Shields, Adam R; Napier, Mary; Luft, J Christopher; Wu, Huali; Zamboni, William C; Wang, Andrew Z; Bear, James E; DeSimone, Joseph M

    2011-01-11

    It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.

  18. 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.

  19. [Impaired hemostasis as a cause of intensified bleeding after heart surgery with extracorporeal blood circulation].

    PubMed

    Morozov, Iu A; Charnaia, M A; Gladysheva, V G

    2004-01-01

    The paper contains the results of a retrospective analysis of causes for an intensified bleeding in patients operated on the heart with artificial blood circulation. An affected hemostasis plasma chain, i.e. insufficiency of blood coagulation factors due to hemodelution, hypofibrinogenemia etc., provoked the above disorder in 39% of patients with a higher postoperative bleeding. Additional reasons for the impaired hemostasis chain included: the "heparin-rebound" phenomenon (3.4%), activation of the secondary fibrinolysis (3.4%) and disseminated intravascular coagulation (DIC) (0.14%). Finally, an undiagnosed inadequate surgical hemostasis provoked an intense bleeding in 19.5% of cases.

  20. [CORRECTION OF BLOOD CIRCULATION IN THE PROSTATE IN PATIENTS WITH CHRONIC PROSTATITIS ASSOCIATED WITH UROGENITAL INFECTIONS].

    PubMed

    Kondrat'eva, Ju S; Nejmark, A I; Zheltikova, Ja D; Subbotin, E A

    2015-01-01

    The aim of the study was to assess the effect of a combined preparation of Vitaprost on blood supply and microcirculation in the prostate gland in 35 patients with chronic infectious urethral prostatitis. The effectiveness of treatment was estimated by a combination of clinical, bacteriological and instrumental diagnostic methods. Transrectal ultrasonography with color Doppler and laser Doppler flowmetry were used to estimate all components of blood circulation in the prostate. Examination results obtained before and after treatment showed better clinical outcomes and improved parameters of blood flow and microcirculation in the prostate in patients receiving Vitapost. These results indicate that combination therapy including Vitaprost is effective in correcting blood flow and microcirculatory disorders of the prostate and can be utilized in the treatment of chronic infectious urethral prostatitis.

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

    PubMed

    Takeuchi, Takashi; Kitagawa, Hiroshi; Harada, Etsumori

    2004-05-01

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

  2. 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.

  3. 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…

  4. 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…

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

    PubMed

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

    2015-12-01

    For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as "accelerated blood clearance (ABC)" where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe(3)O(4) nanoparticles (Fe(3)O(4) @RBC NPs) rely on CD47, which is a "don't eat me" marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-α) receptor. Fe(3)O(4) @RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe(3)O(4) @RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    Liu, Yue; Yin, Huijun; Chen, Keji

    2013-11-01

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

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

    PubMed Central

    Yamakoshi, Yoshiki

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. 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

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

    PubMed

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

    2015-02-06

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

  11. 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.

  12. 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.

  13. 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.

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

    PubMed

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

    2016-07-20

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

  15. 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.

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

    PubMed

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

    2012-06-01

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

  17. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  19. 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.

  20. 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.

  1. Circulating microRNAs as Biomarkers for Detection of Autologous Blood Transfusion

    PubMed Central

    Leuenberger, Nicolas; Schumacher, Yorck Olaf; Pradervand, Sylvain; Sander, Thomas; Saugy, Martial; Pottgiesser, Torben

    2013-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs measured in blood plasma have emerged as specific and sensitive markers of physiological processes and disease. In this study, we investigated whether circulating miRNAs can serve as biomarkers for the detection of autologous blood transfusion, a major doping technique that is still undetectable. Plasma miRNA levels were analyzed using high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after autologous blood transfusion (blood bag storage time 42 days) in 10 healthy subjects and 10 controls without transfusion. Other serum markers of erythropoiesis were determined in the same samples. Our results revealed a distinct change in the pattern of circulating miRNAs. Ten miRNAs were upregulated in transfusion samples compared with control samples. Among these, miR-30b, miR-30c, and miR-26b increased significantly and showed a 3.9-, 4.0-, and 3.0-fold change, respectively. The origin of these miRNAs was related to pulmonary and liver tissues. Erythropoietin (EPO) concentration decreased after blood reinfusion. A combination of miRNAs and EPO measurement in a mathematical model enhanced the efficiency of autologous transfusion detection through miRNA analysis. Therefore, our results lay the foundation for the development of miRNAs as novel blood-based biomarkers to detect autologous transfusion. PMID:23840438

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

    PubMed

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

    2014-10-01

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

  3. Effect of cable cerclage on regional blood circulation in rabbits: a scintigraphic study.

    PubMed

    Karakoyun, Ozgur; Sahin, Ertan; Erol, Mehmet Fatih; Karıksız, Mesut; Küçükkaya, Metin

    2016-12-01

    To evaluate changes in blood circulation of the femoral cortex in rabbits using scintigraphy before and after cable cerclage alone or combined with an intramedullary Kirschner wire. Ten New Zealand rabbits were used. For the right femur, a 2-mm-thick cable was placed around the mid-diaphyseal region and squeezed with a 400-N force and locked with a clip. For the left femur, a 1.8-mm Kirschner wire was inserted retrogradely into the medullary canal, and a 2-mm-thick cable was applied using the same technique. The blood perfusion ratio of the region of interest (ROI) before and after surgery was evaluated using scintigraphy. For the right femurs, the mean ROI perfusion ratio decreased by 45% from 2.51 to 1.37 after intervention (p=0.001). For the left femurs, the mean ROI perfusion ratio decreased by 56% from 2.12 to 0.92 after intervention (p<0.001). The mean ROI perfusion ratio post-intervention was higher in the right than left femurs (p=0.017). Cable cerclage around the femoral cortex significantly decreased blood circulation in the area.

  4. Polyanhydride micelles with diverse morphologies for shape-regulated cellular internalization and blood circulation

    PubMed Central

    Yang, Guang; Wang, Jie; Li, Dan

    2017-01-01

    Abstract Biodegradable amphiphilic poly (ethylene glycol) (PEG) based ether-anhydride terpolymer, consisting of PEG, 1, 3-bis (p-carboxyphenoxy) propane (CPP) and sebacic acid (SA), namely PEG-CPP-SA terpolymer, was employed to self-assemble into micelles by adding water into a solution of the terpolymer in tetrahydrofuran (THF). The shape of polyanhydride micelles can be regulated by simply adjusting the water addition rate, where spherical, rod-like and comb-like micelles can obtained under water addition rate of 20, 3 and 1 ml/h, respectively. The effect of micellar morphologies on the cellular internalization and intracellular distribution were characterized qualitatively with cervical cancer cells (HeLa cells) and hepatoma cells (HepG2 cells) by fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry (FCM) and transmission electron microscopy (TEM). The results reveal that the cellular uptake of micelles are micelle-shape-dependent (rod-like micelles may possess the highest cellular internalization rate) and cell-type-specific. Each endocytic pathway can make a contribution to this process in different degree. Moreover, blood circulation experiments of these micelles were carried out, demonstrating that comb-like micelles have a relatively longer blood circulating feature, which may due to its irregular shape help to increase the sensitivity to fluid forces and allows them to tumble and align with the blood flow. PMID:28596913

  5. 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.

  6. 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

  7. 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

  8. Comparative Analysis of Compatibility Effects on Invigorating Blood Circulation for Cyperi Rhizoma Series of Herb Pairs Using Untargeted Metabolomics

    PubMed Central

    Liu, Pei; Shang, Er-Xin; Zhu, Yue; Yu, Jin-Gao; Qian, Da-Wei; Duan, Jin-Ao

    2017-01-01

    The mutual-assistance compatibility of Cyperi Rhizoma (Xiangfu, XF) and Angelicae Sinensis Radix (Danggui, DG), Chuanxiong Rhizoma (Chuanxiong, CX), Paeoniae Radix Alba (Baishao, BS), or Corydalis Rhizoma (Yanhusuo, YH), found in a traditional Chinese medicine (TCM) named Xiang-Fu-Si-Wu Decoction (XFSWD), can produce synergistic and promoting blood effects. Nowadays, XFSWD has been proved to be effective in activating blood circulation and dissipating blood stasis. However, the role of the herb pairs synergistic effects in the formula were poorly understood. In order to quantitatively assess the compatibility effects of herb pairs, mass spectrometry-based untargeted metabolomics studies were performed. The plasma and urine metabolic profiles of acute blood stasis rats induced by adrenaline hydrochloride and ice water and administered with Cyperi Rhizoma—Angelicae Sinensis Radix (XD), Cyperi Rhizoma—Chuanxiong Rhizoma (XC), Cyperi Rhizoma—Paeoniae Radix Alba (XB), Cyperi Rhizoma—Corydalis Rhizoma (XY) were compared. Relative peak area of identified metabolites was calculated and principal component analysis (PCA) score plot from the potential markers was used to visualize the overall differences. Then, the metabolites results were used with biochemistry indicators and genes expression values as parameters to quantitatively evaluate the compatibility effects of XF series of herb pairs by PCA and correlation analysis. The collective results indicated that the four XF herb pairs regulated glycerophospholipid metabolism, steroid hormone biosynthesis and arachidonic acid metabolism pathway. XD was more prominent in regulating the blood stasis during the four XF herb pairs. This study demonstrated that metabolomics was a useful tool to efficacy evaluation and compatibility effects of TCM elucidation. PMID:29018346

  9. 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.

  10. The role of vasculature and blood circulation in zebrafish swimbladder development

    PubMed Central

    2010-01-01

    Background Recently we have performed a detailed analysis of early development of zebrafish swimbladder, a homologous organ of tetrapod lung; however, the events of swimbladder development are still poorly characterized. Many studies have implicated the role of vascular system in development of many organs in vertebrates. As the swimbladder is lined with an intricate network of blood capillaries, it is of interest to investigate the role of the vascular system during early development of swimbladder. Results To investigate the role of endothelial cells (ECs) and blood circulation during development of the swimbladder, phenotypes of swimbladder were analysed at three different stages (~2, 3 and 5 dpf [day postfertilization]) in cloche (clo) mutant and Tnnt2 morphants, in the background of transgenic lines Et(krt4:EGFP)sq33-2 and Et(krt4:EGFP)sqet3 which express EGFP in the swimbladder epithelium and outer mesothelium respectively. Analyses of the three tissue layers of the swimbladder were performed using molecular markers hb9, fgf10a, acta2, and anxa5 to distinguish epithelium, mesenchyme, and outer mesothelium. We showed that the budding stage was independent of ECs and blood flow, while early epithelial growth, mesenchymal organization and its differentiation into smooth muscle, as well as outer mesothelial organization, were dependent on ECs. Blood circulation contributed to later stage of epithelial growth, smooth muscle differentiation, and organization of the outer mesothelium. Inflation of the swimbladder was also affected as a result of absence of ECs and blood flow. Conclusion Our data demonstrated that the vascular system, though not essential in swimbladder budding, plays an important role in the development of the swimbladder starting from the early growth stage, including mesenchyme organization and smooth muscle differentiation, and outer mesothelial organization, which in turn may be essential for the function of the swimbladder as reflected in its

  11. The role of vasculature and blood circulation in zebrafish swimbladder development.

    PubMed

    Winata, Cecilia Lanny; Korzh, Svetlana; Kondrychyn, Igor; Korzh, Vladimir; Gong, Zhiyuan

    2010-01-14

    Recently we have performed a detailed analysis of early development of zebrafish swimbladder, a homologous organ of tetrapod lung; however, the events of swimbladder development are still poorly characterized. Many studies have implicated the role of vascular system in development of many organs in vertebrates. As the swimbladder is lined with an intricate network of blood capillaries, it is of interest to investigate the role of the vascular system during early development of swimbladder. To investigate the role of endothelial cells (ECs) and blood circulation during development of the swimbladder, phenotypes of swimbladder were analysed at three different stages (approximately 2, 3 and 5 dpf [day postfertilization]) in cloche (clo) mutant and Tnnt2 morphants, in the background of transgenic lines Et(krt4:EGFP)sq33-2 and Et(krt4:EGFP)sqet3 which express EGFP in the swimbladder epithelium and outer mesothelium respectively. Analyses of the three tissue layers of the swimbladder were performed using molecular markers hb9, fgf10a, acta2, and anxa5 to distinguish epithelium, mesenchyme, and outer mesothelium. We showed that the budding stage was independent of ECs and blood flow, while early epithelial growth, mesenchymal organization and its differentiation into smooth muscle, as well as outer mesothelial organization, were dependent on ECs. Blood circulation contributed to later stage of epithelial growth, smooth muscle differentiation, and organization of the outer mesothelium. Inflation of the swimbladder was also affected as a result of absence of ECs and blood flow. Our data demonstrated that the vascular system, though not essential in swimbladder budding, plays an important role in the development of the swimbladder starting from the early growth stage, including mesenchyme organization and smooth muscle differentiation, and outer mesothelial organization, which in turn may be essential for the function of the swimbladder as reflected in its eventual inflation.

  12. Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction.

    PubMed

    Merx, Marc W; Gorressen, Simone; van de Sandt, Annette M; Cortese-Krott, Miriam M; Ohlig, Jan; Stern, Manuel; Rassaf, Tienush; Gödecke, Axel; Gladwin, Mark T; Kelm, Malte

    2014-01-01

    Nitric oxide (NO) derived from endothelial NO synthase (NOS3) plays a central role in myocardial ischemia/reperfusion (I/R)-injury. Subsets of circulating blood cells, including red blood cells (RBCs), carry a NOS3 and contribute to blood pressure regulation and RBC nitrite/nitrate formation. We hypothesized that the circulating blood born NOS3 also modulates the severity of myocardial infarction in disease models. We cross-transplanted bone marrow in wild-type and NOS3(-/-) mice with wild-type mice, producing chimeras expressing NOS3 only in vascular endothelium (BC-/EC+) or in both blood cells and vascular endothelium (BC+/EC+). After 60-min closed-chest coronary occlusion followed by 24 h reperfusion, cardiac function, infarct size (IS), NOx levels, RBCs NO formation, RBC deformability, and vascular reactivity were assessed. At baseline, BC-/EC+ chimera had lower nitrite levels in blood plasma (BC-/EC+: 2.13 ± 0.27 μM vs. BC+/EC+ 3.17 ± 0.29 μM; *p < 0.05), reduced DAF FM associated fluorescence within RBCs (BC-/EC+: 538.4 ± 12.8 mean fluorescence intensity (MFI) vs. BC+/EC+: 619.6 ± 6.9 MFI; ***p < 0.001) and impaired erythrocyte deformability (BC-/EC+: 0.33 ± 0.01 elongation index (EI) vs. BC+/EC+: 0.36 ± 0.06 EI; *p < 0.05), while vascular reactivity remained unaffected. Area at risk did not differ, but infarct size was higher in BC-/EC+ (BC-/EC+: 26 ± 3 %; BC+/EC+: 14 ± 2 %; **p < 0.01), resulting in decreased ejection fraction (BC-/EC+ 46 ± 2 % vs. BC+/EC+: 52 ± 2 %; *p < 0.05) and increased end-systolic volume. Application of the NOS inhibitor S-ethylisothiourea hydrobromide was associated with larger infarct size in BC+/EC+, whereas infarct size in BC-/EC+ mice remained unaffected. Reduced infarct size, preserved cardiac function, NO levels in RBC and RBC deformability suggest a modulating role of circulating NOS3 in an acute model of myocardial I/R in chimeric mice.

  13. 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.

  14. [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.

  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. Filtration and Analysis of Circulating Cancer Associated Cells from the Blood of Cancer Patients.

    PubMed

    Tang, Cha-Mei; Zhu, Peixuan; Li, Shuhong; Makarova, Olga V; Amstutz, Platte T; Adams, Daniel L

    2017-01-01

    Filtration is one of the most efficient methods to remove red and white blood cells from whole blood, while retaining larger cells on the surface of the filter. Precision pore microfilters, such as the CellSieve™ microfilters, are ideally suited for this purpose, as they are strong, with uniform pore size and distribution, and have low fluorescent background required for microscopic image analysis. We present a system to implement the filtration of whole blood in combination with CellSieve™ microfilters that is simple and straightforward to use. Being that the blood of cancer patients often contains both tumor cells and stromal cells associated with cancer that are larger than normal blood cells, microfiltration shows great promise in better understanding these cell types. Accurate identification and characterization of cancer associated cells has led to increased specificity as it relates to CTCs and epithelial-mesenchymal transition cells (EMTs) and enabled the identification of previously unknown cell types, such as cancer associated macrophage-like cells (CAMLs). Using a system that isolates both CTCs and circulating stromal cells, clinicians can better diagnose cancer patients to determine therapy, monitor treatment, and watch for recurrence.

  17. 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

  18. 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.

  19. 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.

  20. Detection of circulating tumor cells from cryopreserved human sarcoma peripheral blood mononuclear cells.

    PubMed

    Li, Heming; Meng, Qing H; Noh, Hyangsoon; Batth, Izhar Singh; Somaiah, Neeta; Torres, Keila E; Xia, Xueqing; Wang, Ruoyu; Li, Shulin

    2017-09-10

    Circulating tumor cells (CTCs) enter the vasculature or lymphatic system after shedding from the primary tumor. CTCs may serve as "seed" cells for tumor metastasis. The utility of CTCs in clinical applications for sarcoma is not fully investigated, partly owing to the necessity for fresh blood samples and the lack of a CTC-specific antibody. To overcome these drawbacks, we developed a technique for sarcoma CTCs capture and detection using cryopreserved peripheral blood mononuclear cells (PBMCs) and our proprietary cell-surface vimentin (CSV) antibody 84-1, which is specific to tumor cells. This technique was validated by sarcoma cell spiking assay, matched CTCs comparison between fresh and cryopreserved PBMCs, and independent tumor markers in multiple types of sarcoma patient blood samples. The reproducibility was maximized when cryopreserved PBMCs were prepared from fresh blood samples within 2 h of the blood draw. In summary, as far as we are aware, ours is the first report to capture and detect CTCs from cryopreserved PBMCs. Further validation in other types of tumor may help boost the feasibility and utility of CTC-based diagnosis in a centralized laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. [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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. [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.

  7. 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.

  8. 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.

  9. Targeting of a Mutant Plasminogen Activator to Circulating Red Blood Cells for Prophylactic Fibrinolysis

    PubMed Central

    Zaitsev, Sergei; Spitzer, Dirk; Murciano, Juan-Carlos; Ding, Bi-Sen; Tliba, Samira; Kowalska, M. Anna; Bdeir, Khalil; Kuo, Alice; Stepanova, Victoria; Atkinson, John P.; Poncz, Mortimer; Cines, Douglas B.

    2010-01-01

    Chemical coupling to carrier red blood cells (RBCs) converts tissue type plasminogen activator (tPA) from a problematic therapeutic into a safe agent for thromboprophylaxis. The goal of this study was to develop a more clinically relevant recombinant biotherapeutic by fusing a mutant tPA with a single-chain antibody fragment (scFv) with specificity for glycophorin A (GPA) on mouse RBCs. The fusion construct (anti-GPA scFv/PA) bound specifically to mouse but not human RBCs and activated plasminogen; this led to rapid and stable attachment of up to 30,000 copies of anti-GPA scFv/PA per mouse RBC that were thereby endowed with high fibrinolytic activity. Binding of anti-GPA scFv/PA neither caused RBC aggregation, hemolysis, uptake in capillary-rich lungs or in the reticuloendothelial system nor otherwise altered the circulation of RBCs. Over 40% of labeled anti-GPA scFv/PA injected in mice bound to RBC, which markedly prolonged its intravascular circulation and fibrinolytic activity compared with its nontargeted PA counterpart, anti-GPA scFv/PA, but not its nontargeted PA analog, prevented thrombotic occlusion in FeCl3 models of vascular injury. These results provide proof-of-principle for the development of a recombinant PA variant that binds to circulating RBC and provides thromboprophylaxis by use of a clinically relevant approach. PMID:19952305

  10. Fjord circulation promotes significant glacier-wide submarine melting at a west Greenland tidewater glacier

    NASA Astrophysics Data System (ADS)

    Slater, Donald A.; Straneo, Fiamma; Das, Sarah B.; Nienow, Peter W.

    2017-04-01

    In recent decades, rapid change at Greenland's marine-terminating glaciers has significantly impacted the contribution of the ice sheet to sea level. While these changes have been widely linked to a warming of the ocean around Greenland, process understanding linking ocean forcing to glacier response, for example by submarine melting, remains at an early stage. The most rapid submarine melting likely occurs where buoyant plumes, initiated by subglacial discharge, rise up tidewater glacier calving fronts. Plumes have therefore received much attention, yet a plume typically occupies only a small fraction of the submerged calving front area. Thus melting within the plume itself may be a small contributor to the front-wide melting experienced by the glacier. A plume may however promote melting over a much larger area by inducing a fjord-scale circulation which, by increasing water velocities at the ice/ocean interface, can give rise to increased melting over the entire glacier face. Here we address this fjord-scale, plume-driven circulation and its impact on submarine melting by combining observations collected within 100 m of marine-terminating Saqqarliup Sermia in west Greenland with high-resolution fjord modelling using the MITgcm. Both field data and modelling show that water from the main plume flows away from the glacier as a subsurface jet, and that entrainment into this jet generates regions of fjord water recirculating back towards the glacier. The modelling further suggests that these recirculations drive elevated across-glacier water motion thereby promoting significant submarine melting over the full 4 km-width of the calving front, resulting in total melt volumes which substantially exceed those generated directly by the relatively narrow plume. Our results highlight the value of combining detailed field observations with modelling and demonstrate how the secondary fjord circulation generated by plumes may play a significant role in driving submarine

  11. 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

  12. Evaluation of INK4A promoter methylation using pyrosequencing and circulating cell-free DNA from patients with hepatocellular carcinoma

    PubMed Central

    Kirk, Jason L.; Merwat, Shehzad N.; Ju, Hyunsu; Soloway, Roger D.; Wieck, Lucas R.; Li, Albert; Okorodudu, Anthony O.; Petersen, John R.; Abdulla, Nihal E.; Duchini, Andrea; Cicalese, Luca; Rastellini, Cristiana; Hu, Peter C.; Dong, Jianli

    2015-01-01

    Background Hyper-methylation of CpG dinucleotides in the promoter region of inhibitor of cyclin-dependent kinase 4A (INK4A) has been reported in 60%–80% of hepatocellular carcinoma (HCC). As INK4A promoter hypermethylation event occurs early in HCC progression, the quantification of INK4A promoter methylation in blood sample may represent a useful biomarker for non-invasive diagnosis and prediction of response to therapy. Methods We examined INK4A promoter methylation using circulating cell-free DNA (ccfDNA) in a total of 109 serum specimens, including 66 HCC and 43 benign chronic liver diseases. Methylation of the individual seven CpG sites was examined using pyrosequencing. Results Our results showed that there were significantly higher levels of methylated INK4A in HCC specimens than controls and that the seven CpG sites had different levels of methylation and might exist in different PCR amplicons. The area under receiver operating characteristic (ROC) curve was 0.82, with 65.3% sensitivity and 87.2% specificity at 5% (LOD), 39.0% sensitivity and 96.5% specificity at 7% LOD, and 20.3% sensitivity and 98.8% specificity at 10% LOD, respectively. Conclusions Our results support additional studies incorporating INK4A methylation testing of ccfDNA to further validate the diagnostic, predictive, and prognostic characteristics of this biomarker in HCC patients. The knowledge of the existence of epi-alleles should help improve assay design to maximize detection. PMID:24406287

  13. Reduction in blood product usage associated with routine use of mini bypass systems in extracorporeal circulation.

    PubMed

    Perthel, M; Klingbeil, A; El-Ayoubi, L; Gerick, M; Laas, J

    2007-01-01

    The objective of this study is to investigate the hypothesis that a reduced prime extracorporeal circulation (ECC) system and ensuing reduction in patient hemodilution can affect blood product use. We performed a prospective, randomized study from a group of 60 consecutive coronary artery bypass graft (CABG) patients, comparing blood product usage and postoperative bleeding in 30 mini bypass systems (n = 30) to 30 conventional systems (n = 30). The patient demographics in terms of patient weight, height, age, preoperative hemoglobin, preoperative hematocrit, BSA, ejection fraction, and NYHA were not statistically significant. Blood product use, including fresh frozen plasma (FFP) and homolgous blood transfusions was tracked through the operating theater and into the intensive care unit. In the mini bypass group, while no homologous blood transfusions were given in the OR, 27% of the patients received at least one unit of homologous blood. In the control group, 43% of the patients received at least one unit of blood in the OR or in the ICU and there was a stastistically-significant 38% reduction in homologous blood product use (p = 0.05). For the patients who received homologous blood, there was also a significant reduction in transfused volume (0.53 +/- 0.90 units blood mini bypass vs 1.3 +/- 1.93 units conventional, p < 0.05). In terms of FFP, there was also a stastistically significant difference between the two groups (0 units transfused in mini bypass group vs 3 patients receiving one unit FFP in the control group, p < 0.001). Cumulative postoperative bleeding during the ICU stay was also evaluated, yielding a significant reduction (365 +/- 495 ml mini bypass vs 825 +/- 975 ml conventional, p < 0.05). Mini bypass reduces on-pump hemodilution and, therefore, donor blood usage in routine CABG patients as compared to conventional ECC circuits and can reduce postoperative bleeding as compared to a traditional system. The mini bypass system is safe in routine

  14. 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.

  15. 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

  16. Meshless bubble filter using ultrasound for extracorporeal circulation and its effect on blood.

    PubMed

    Mino, Koji; Imura, Masato; Koyama, Daisuke; Omori, Masayoshi; Kawarabata, Shigeki; Sato, Masafumi; Watanabe, Yoshiaki

    2015-02-01

    A bubble filter with no mesh structure for extracorporeal circulation using ultrasound was developed. Hemolysis was evaluated by measuring free hemoglobin (FHb). FHb in 120 mL of bovine blood was measured in acoustic standing-wave fields. With a sound pressure amplitude of 60 kPa at driving frequencies of 1 MHz, 500 kHz and 27 kHz for 15 min. FHb values were 641.6, 2575 and 8903 mg/dL, respectively. Thus, hemolysis was inhibited with higher driving frequencies when the same sound pressure amplitude was applied. An ultrasound bubble filter with a resonance frequency of 1 MHz was designed. The filtering characteristics of the flowing microbubbles were investigated with a circulation system using bovine blood with a flow rate of 5.0 L/min. Approximately 99.1% of microbubbles were filtered with 250 kPa and a flow of 5.0 L/min. Hemolysis decreased as the sound pressure decreased; FHb values were 225.8 and 490.7 mg/dL when using 150 and 200 kPa, respectively. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  17. [Auxiliary blood circulation and the artificial heart: forty years of development].

    PubMed

    Tolpekin, V E; Shumakov, D V

    2006-01-01

    The article summarizes forty-year experience in working over the problem of the artificial heart and auxiliary blood circulation in Laboratory and later Research Institute of Transplantology and Artificial Organs. This work has resulted in the development of balloon pumps for intraaortic contrapulsation, the technique of balloon installation, and indications to its application. The results of the clinical application of the method in patients with various pathologies have been estimated. Preclinically, left ventricular bypass techniques have been tested on more than twenty models of membrane type artificial ventricles. The results of the clinical application of left ventricular bypass have been analyzed. The authors adduce data on the development of the thermomechanical implantable bypass system "Micron-M". After achieving 100-day survival of calves with an artificial heart, an artificial heart with external power supply was used as a "bridge" to heart transplantation, but there was only one patient in whom transplantation was performed. The authors consider development of implantable auxiliary blood circulation devices and the artificial heart to be of great prospective value.

  18. Effects of therapeutic ultrasound on intramuscular blood circulation and oxygen dynamics.

    PubMed

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

    2014-01-01

    This study aimed to clarify the effects of therapeutic ultrasound on intramuscular local blood circulation (and oxygen dynamics) using near-infrared spectroscopy (NIRS). The participants were 11 healthy males. 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/cm(2), 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. 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). 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.

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

    PubMed

    Kubo, K

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    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 similar fashion to a target model and demonstrated within-group dialogic interaction patterns. It was found that statements associated with DLA contributed to the collaborative group dynamics by providing cognitive scaffolding and enabling critical monitoring, which together facilitated model development and students' participation and understanding. In the model generation phase, the skills demonstrated indicated the use of statements associated with DLA as one student focused on the principles of blood circulation, thereby providing scaffolding for the other students. These students then generated another sub-model. In the model elaboration phase, statements associated with DLA elements such as request information of mechanism (AQ-a) and resolve discrepancies in knowledge (AQ-b) provided students with metacognitive scaffolding and enabled them to show their deep cognitive participation. Moreover, statements associated with DLA elements such as asking questions or metacognitive activity enabled the students to monitor others' models or ideas critically, showing that active cognitive interaction was taking place within the group. These findings reveal that individual learning approaches will bring a synergistic effect to a group modeling process and can lead to practical educational insights for educators seeking to use lessons based on group modeling.

  1. 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.

  2. 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

  3. 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.

  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. 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.

  6. 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

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

    PubMed

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

    2014-06-01

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

  8. Maternal body-mass index and cord blood circulating endothelial colony-forming cells.

    PubMed

    Moreno-Luna, Rafael; Muñoz-Hernandez, Rocio; 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

    2014-03-01

    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 nonpathologic pregnancies. We measured the level of ECFCs in the cord blood of neonates (n = 27) born from non-obese healthy mothers with nonpathologic 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. We observed variation in ECFC abundance among subjects and found a positive correlation between prepregnancy maternal BMI and ECFC content (r = 0.51, P = .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/m(2) and BMI between 25-30 kg/m(2), including the ability to form vascular networks in vivo. 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 pathologic pregnancies. Copyright © 2014 Mosby, Inc. All rights reserved.

  9. 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.

  10. [Analysis on anti-hepatoma effect of medicine invigorating blood circulation and eliminating blood stasis based on warm-pungent-liver efficiency network].

    PubMed

    Gu, Hao; Ma, Li; Yuan, Bin; Zhang, Yan-Ling; Wang, Yun; Qiao, Yan-Jiang

    2014-07-01

    The efficiency network is a complicated network for revealing the efficient mechanism of traditional Chinese medicines (TCMs) and relations among efficiencies. The efficiency-property relations were used to establish a warm-pungent-liver efficiency network to explain the principle of treating hepatoma with medicines invigorating blood circulation and eliminating blood stasis. Safflower, a warm-pungent medicine distributing along the live meridian, was taken for example to discuss the efficiency network' s application in the identification of active ingredients of TCMs and the combination. In the early stage of this study, combined warm-pungent-liver medicines distributed along the liver meridian and invigorating blood circulation and eliminating blood stasis were taken as the study objects to collect the pharmacological effect data of warm-pungent-liver medicines and obtain the pharmacological effect combinations with the highest blood circulation-invigorating association by the association rules and the chi-square test. The pharmacological target data recorded in the DrugBank database is used to establish the warm-pungent-liver efficiency network according to the principle line of "efficiency-property-pharmacology-target-protein interaction" under the background of the protein interaction network. The blood circulation-invigorating medicines could directly treat hepatoma by impacting protooncogene, cancer suppressor gene, cell apoptosis and anti-inflammation, and indirectly treat hepatoma by resisting coagulation and adhesion, regulating local blood circulation, preventing cancer cell metastasis and enhancing the tissues' sensitivity to the anticancer drugs. Among the active ingredients of safflower screened based on the blood circulation-invigorating network targets, carthamin yellow, quercetin and luteolin have been proved to have the anti-hepatoma effect in literatures, which indicated the reliability of this study's results and the purpose of the efficiency

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

    PubMed

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

    2013-10-01

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

  12. 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.

  13. A cell transportation solution that preserves live circulating tumor cells in patient blood samples.

    PubMed

    Stefansson, Steingrimur; Adams, Daniel L; Ershler, William B; Le, Huyen; Ho, David H

    2016-05-06

    Circulating tumor cells (CTCs) are typically collected into CellSave fixative tubes, which kills the cells, but preserves their morphology. Currently, the clinical utility of CTCs is mostly limited to their enumeration. More detailed investigation of CTC biology can be performed on live cells, but obtaining live CTCs is technically challenging, requiring blood collection into biocompatible solutions and rapid isolation which limits transportation options. To overcome the instability of CTCs, we formulated a sugar based cell transportation solution (SBTS) that stabilizes cell viability at ambient temperature. In this study we examined the long term viability of human cancer cell lines, primary cells and CTCs in human blood samples in the SBTS for transportation purposes. Four cell lines, 5 primary human cells and purified human PBMCs were tested to determine the viability of cells stored in the transportation solution at ambient temperature for up to 7 days. We then demonstrated viability of MCF-7 cells spiked into normal blood with SBTS and stored for up to 7 days. A pilot study was then run on blood samples from 3 patients with metastatic malignancies stored with or without SBTS for 6 days. CTCs were then purified by Ficoll separation/microfilter isolation and identified using CTC markers. Cell viability was assessed using trypan blue or CellTracker™ live cell stain. Our results suggest that primary/immortalized cell lines stored in SBTS remain ~90% viable for > 72 h. Further, MCF-7 cells spiked into whole blood remain viable when stored with SBTS for up to 7 days. Finally, live CTCs were isolated from cancer patient blood samples kept in SBTS at ambient temperature for 6 days. No CTCs were isolated from blood samples stored without SBTS. In this proof of principle pilot study we show that viability of cell lines is preserved for days using SBTS. Further, this solution can be used to store patient derived blood samples for eventual isolation of viable CTCs after

  14. 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

  15. 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

  16. Influence of passive leg movements on blood circulation on the tilt table in healthy adults

    PubMed Central

    Czell, David; Schreier, Reinhard; Rupp, Rüdiger; Eberhard, Stephen; Colombo, Gery; Dietz, Volker

    2004-01-01

    Background One problem in the mobilization of patients with neurological diseases, such as spinal cord injury, is the circulatory collapse that occurs while changing from supine to vertical position because of the missing venous pump due to paralyzed leg muscles. Therefore, a tilt table with integrated stepping device (tilt stepper) was developed, which allows passive stepping movements for performing locomotion training in an early state of rehabilitation. The aim of this pilot study was to investigate if passive stepping and cycling movements of the legs during tilt table training could stabilize blood circulation and prevent neurally-mediated syncope in healthy young adults. Methods In the first experiment, healthy subjects were tested on a traditional tilt table. Subjects who had a syncope or near-syncope in this condition underwent a second trial on the tilt stepper. In the second experiment, a group of healthy subjects was investigated on a traditional tilt table, the second group on the tilt ergometer, a device that allows cycling movements during tilt table training. We used the chi-square test to compare the occurrence of near-syncope/syncope in both groups (tilt table/tilt stepper and tilt table/tilt ergometer) and ANOVA to compare the blood pressure and heart rate between the groups at the four time intervals (supine, at 2 minutes, at 6 minutes and end of head-up tilt). Results Separate chi-square tests performed for each experiment showed significant differences in the occurrence of near syncope or syncope based on the device used. Comparison of the two groups (tilt stepper/ tilt table) in experiment one (ANOVA) showed that blood pressure was significantly higher at the end of head-up tilt on the tilt stepper and on the tilt table there was a greater increase in heart rate (2 minutes after head-up tilt). Comparison of the two groups (tilt ergometer/tilt table) in experiment 2 (ANOVA) showed that blood pressure was significantly higher on the tilt

  17. [Clinical study on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation].

    PubMed

    Yang, Kun; Cai, Sheng-Chao; Zhu, Cai-Feng; Fei, Ai-Hua; Qin, Xiao-Feng; Xia, Jian-Guo

    2014-06-01

    To observe the efficacy on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation so as to provide the effective clinical therapeutic methods for osteoporosis. Sixty cases of primary osteoporosis were randomized into a spreading moxibustion group (30 cases) and a calcium tablet group (30 cases). In the calcium tablet group, caltrate was prescribed for oral administration, 600 mg per day. In the spreading moxibustion group, on the basis of the treatment as the calcium tablet group, the spreading moxibustion was applied at Dazhui (GV 14) to Yaoshu (GV 2) for warming yang and activating blood circulation. The duration of treatment was 12 weeks. Visual analogue scale (VAS) score, TCM clinical symptom score and bone mineral density (BMD) were observed and compared before and after treatment in the patients between the two groups. VAS scores were reduced apparently after treatment in the two groups (both P < 0.01) and the results in the spreading moxibustion group were obviously superior to that in the calcium tablet group (2.36 +/- 0.43 vs 4.52 +/- 0.35, P < 0.01). BMD were all increased in the two groups (P < 0.05, P < 0.01) and the results in the spreading moxibustion group were superior to those in the calcium tablet group (both P < 0.05). The total clinical effective rate was 86.67% (26/30) in the spreading moxibustion group, apparently better than 63.33% (19/30) in the calcium tablet group (P < 0.05). TCM clinical symptom scores after treatment were all reduced apparently in the two groups (both P < 0.01), and the result in the spreading moxibustion group was obviously superior to that in the calcium tablet group (4.72 +/- 1.90 vs 6.82 +/- 2.30, P < 0.01). The total effective rate of TCM symptoms was 93.33% (28/30) in the spreading moxibustion group, apparently better than 70.00% (21/30) in the calcium tablet group (P < 0.05). The combined therapy of spreading moxibustion for warming yang and activating blood

  18. Blood ionized magnesium concentrations during cardiopulmonary bypass and their correlation with other circulating cations.

    PubMed

    Aziz, S; Haigh, W G; Van Norman, G A; Kenny, R J; Kenny, M A

    1996-01-01

    The recent introduction of new measurement technology (using ion specific electrodes) makes intraoperative evaluation of blood ionized magnesium (Mg2+, or iMg)--the bioactive fraction of circulation magnesium--possible. The goals of this study were: (1) to examine the longitudinal pattern(s) of change in blood iMg during cardiopulmonary bypass (CPB); and (2) to determine the relationship of iMg to Ca2+ (iCa), K, pH, Na, and hematocrit (Hct) during CPB. Blood was collected serially before, during, and after CPB on 30 patients undergoing elective coronary artery bypass graft procedures and the iMg was measured with an AVL Scientific Corp., model 988-4 instrument. Overall, 73% of iMg results were abnormally low, 50% during CPB. Some cases had both hypo- and hyperionized magnesemic episodes. There were low iCa during CPB in 97% of cases. Using Spearman's rank order correlations and p < 0.05, iMg and K were directly correlated before, during, and after bypass, suggesting their parallel movement between tissue and blood. iMg and iCa were directly correlated before, and inversely correlated after, CPB, but unassociated during bypass. iMg and Na were inversely correlated after bypass in all cases. iMg was inversely correlated to pH and positively correlated to Hct during CPB only, and only in patients with concurrent association of iMg and iCa. Blood iMg depletion occurs frequently in CPB patients. iMg changes are not readily predictable. The association of intraoperative iMg depletion with postsurgical atrial fibrillation--reported to have a hypomagnesemic connection- should be investigated.

  19. 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

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  2. NMDA Receptor Activity in Circulating Red Blood Cells: Methods of Detection.

    PubMed

    Makhro, Asya; Kaestner, Lars; Bogdanova, Anna

    2017-01-01

    Abundance and activity of N-methyl-D-aspartate (NMDA) in circulating red blood cells contributes to the maintenance of intracellular Ca(2+) in these cells and, by doing that, controls red cell volume, membrane stability, and O2 carrying capacity. Detection of the NMDA receptor activity in red blood cells is challenging as the number of its copies is low and shows substantial cell-to-cell heterogeneity. Receptor abundance is reliably assessed using the radiolabeled antagonist ([(3)H]MK-801) binding technique. Uptake of Ca(2+) following the NMDA receptor activation is detected in cells loaded with Ca(2+)-sensitive fluorescent dye Fluo-4 AM. Both microfluorescence live-cell imaging and flow cytometry may be used for fluorescence intensity detection. Automated patch clamp is currently used for recording of electric currents triggered by the stimulation of the NMDA receptor. These currents are mediated by the Ca(2+)-sensitive K(+) (Gardos) channels that open upon Ca(2+) uptake via the active NMDA receptor. Furthermore, K(+) flux through the Gardos channels induced by the NMDA receptor stimulation in red blood cells may be detected using unidirectional K(+)((86)Rb(+)) influx.

  3. 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.

  4. 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.

  5. Morphological changes in vascular and circulating blood cells following exposure to detergent sclerosants.

    PubMed

    Cooley-Andrade, O; Connor, D E; Ma, D D F; Weisel, J W; Parsi, K

    2016-04-01

    To investigate morphological changes in vascular and circulating blood cells following exposure to detergent sclerosants sodium tetradecyl sulfate and polidocanol. Samples of whole blood, isolated leukocytes, platelets, endothelial cells, and fibroblasts were incubated with varying concentrations of sclerosants. Whole blood smears were stained with Giemsa and examined by light and bright field microscopy. Phalloidin and Hoechst stains were used to analyze cytoplasmic and nuclear morphology by fluorescence microscopy. Endothelial cell and fibroblasts were analyzed by live cell imaging. Higher concentrations of sclerosants induced cell lysis. Morphological changes in intact cells were observed at sublytic concentrations of detergents. Low concentration sodium tetradecyl sulfate induced erythrocyte acanthocytosis and macrocytosis, while polidocanol induced Rouleaux formation and increased the population of target cells and stomatocytes. Leukocytes showed swelling, blebbing, vacuolation, and nuclear degradation following exposure to sodium tetradecyl sulfate, while polidocanol induced pseudopodia formation, chromatin condensation, and fragmentation. Platelets exhibited pseudopodia with sodium tetradecyl sulfate and a "fried egg" appearance with polidocanol. Exposure to sodium tetradecyl sulfate resulted in size shrinkage in both endothelial cell and fibroblasts, while endothelial cell developed distinct spindle morphology. Polidocanol induced cytoplasmic microfilament bundles in both endothelial cell and fibroblasts. Patchy chromatin condensation was observed following exposure of fibroblasts to either agent. Detergent sclerosants are biologically active at sublytic concentrations. The observed morphological changes are consistent with cell activation, apoptosis, and oncosis. The cellular response is concentration dependent, cell-specific, and sclerosant specific. © The Author(s) 2015.

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

    PubMed

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

    2014-10-01

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

  7. 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

  8. PEGylation of Vesicular Stomatitis Virus Extends Virus Persistence in Blood Circulation of Passively Immunized Mice

    PubMed Central

    Tesfay, Mulu Z.; Kirk, Amber C.; Hadac, Elizabeth M.; Griesmann, Guy E.; Federspiel, Mark J.; Barber, Glen N.; Henry, Stephen M.; Peng, Kah-Whye

    2013-01-01

    We are developing oncolytic vesicular stomatitis viruses (VSVs) for systemic treatment of multiple myeloma, an incurable malignancy of antibody-secreting plasma cells that are specifically localized in the bone marrow. One of the presumed advantages for using VSV as an oncolytic virus is that human infections are rare and preexisting anti-VSV immunity is typically lacking in cancer patients, which is very important for clinical success. However, our studies show that nonimmune human and mouse serum can neutralize clinical-grade VSV, reducing the titer by up to 4 log units in 60 min. In addition, we show that neutralizing anti-VSV antibodies negate the antitumor efficacy of VSV, a concern for repeat VSV administration. We have investigated the potential use of covalent modification of VSV with polyethylene glycol (PEG) or a function-spacer-lipid (FSL)–PEG construct to inhibit serum neutralization and to limit hepatosplenic sequestration of systemically delivered VSV. We report that in mice passively immunized with neutralizing anti-VSV antibodies, PEGylation of VSV improved the persistence of VSV in the blood circulation, maintaining a more than 1-log-unit increase in VSV genome copies for up to 1 h compared to the genome copy numbers for the non-PEGylated virus, which was mostly cleared within 10 min after intravenous injection. We are currently investigating if this increase in PEGylated VSV circulating half-life can translate to increased virus delivery and better efficacy in mouse models of multiple myeloma. PMID:23325695

  9. Nanocapsules of therapeutic proteins with enhanced stability and long blood circulation for hyperuricemia management.

    PubMed

    Zhang, Xiaopei; Xu, Duo; Jin, Xin; Liu, Gan; Liang, Sheng; Wang, Hui; Chen, Wei; Zhu, Xinyuan; Lu, Yunfeng

    2017-06-10

    Among a broad spectrum of medical treatments, protein therapeutics holds tremendous opportunities for the treatment of metabolic disorders, cancer, autoimmune diseases and etc. Broad adaption of protein therapeutics, however, still remain challenging, not only because of poor protein stability, but they also experience fast clearance after administrated and elicit immune responses, resulting in undesirable biodistribution and short blood residence time. In this study, we demonstrate a novel protein delivery method via encapsulating therapeutic proteins within thin shells of poly(N-vinylpyrrolidone) (PVP), which leads to significantly improved protein stability, reduced macrophage uptake, prolonged circulation time and reduced immunogenicity. Exemplified with urate oxidase (UOx), the enzyme used for hyperuricemia treatment, as-formed UOx nanocapsules, n(UOx), exhibits enhanced stability, more significant therapeutic effects, and a more than 10-fold improvement in circulation time when compared with native UOx. This technology not only demonstrates the use of UOx nanocapsules for hyperuricemia management, but also provides a general approach for a broad spectrum of therapeutic proteins for in vivo applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [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.

  11. 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.

  12. [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.

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

    PubMed

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

    2013-01-01

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

  14. [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.

  15. [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.

  16. Effects of gelucire content on stability, macrophage interaction and blood circulation of nanoparticles engineered from nanoemulsions.

    PubMed

    Wehrung, Daniel; Geldenhuys, Werner J; Oyewumi, Moses O

    2012-06-01

    The main objective of the study is to investigate the efficacy of Gelucire 44/14 (gelucire) in facilitating formation of cetyl alcohol (CA)-based nanoparticle (NP) and to assess the effects on key NP properties and functions. NPs from oil-in-water nanoemulsion precursors were prepared using binary mixtures of CA and gelucire (CA/gelucire) containing gelucire at 0, 25, 50 and 75% (w/w). The sizes of gelucire-based NPs (128-183 nm) were five times lower than control NPs (made without gelucire). All the NPs (with or without gelucire component) did not activate macrophages as monitored by reactive oxygen species production. Results from differential scanning calorimetry, FT-IR and multimodal light scattering measurements demonstrated the involvement of gelucire component in achieving homogeneous CA/gelucire particle populations that were stable on storage. The P-glycoprotein (P-gp) function assay in MES-Dx5 cells showed the potential of gelucire-based NPs in inhibiting rhodamine 123 efflux. Similarly, the extent of NP uptake by macrophage (RAW 264.7 cell) was dependent on the amount of gelucire component (inverse relationship; R(2)=0.996). NPs made with CA/gelucire mixture (at 50%, w/w gelucire) were the most effective in blood circulation studies in BALB/c mice. Additional studies with paclitaxel-loaded NPs demonstrated that the retention of gelucire-based NPs in blood circulation was comparable to NPs coated with DSPE-PEG(2000) (p>0.6). The over-all work indicated the potential efficacy of gelucire as a safe and biocompatible excipient that can serve multiple functions in enhancing the performance of lipid-based NP drug delivery systems. Published by Elsevier B.V.

  17. 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

  18. PEGylation of bacteriophages increases blood circulation time and reduces T‐helper type 1 immune response

    PubMed Central

    Kim, Kwang‐Pyo; Cha, Jeong‐Dan; Jang, Eun‐Hye; Klumpp, Jochen; Hagens, Steven; Hardt, Wolf‐Dietrich; Lee, Kyung‐Yeol; Loessner, Martin J.

    2008-01-01

    Summary The increasing occurrence of antibiotic‐resistant pathogens is of growing concern, and must be counteracted by alternative antimicrobial treatments. Bacteriophages represent the natural enemies of bacteria. However, the strong immune response following application of phages and rapid clearance from the blood stream are hurdles which need to be overcome. Towards our goal to render phages less immunogenic and prolong blood circulation time, we have chemically modified intact bacteriophages by conjugation of the non‐immunogenic polymer monomethoxy‐polyethylene glycol (mPEG) to virus proteins. As a proof of concept, we have used two different polyvalent and strictly virulent phages of the Myoviridae, representing typical candidates for therapeutical approaches: Felix‐O1 (infects Salmonella) and A511 (infects Listeria). Loss of phage infectivity after PEGylation was found to be proportional to the degree of modification, and could be conveniently controlled by adjusting the PEG concentration. When injected into naïve mice, PEGylated phages showed a strong increase in circulation half‐life, whereas challenge of immunized mice did not reveal a significant difference. Our results suggest that the prolonged half‐life is due to decreased susceptibility to innate immunity as well as avoidance of cellular defence mechanisms. PEGylated viruses elicited significantly reduced levels of T‐helper type 1‐associated cytokine release (IFN‐γ and IL‐6), in both naïve and immunized mice. This is the first study demonstrating that PEGylation can increases survival of infective phage by delaying immune responses, and indicates that this approach can increase efficacy of bacteriophage therapy. PMID:21261844

  19. Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

    PubMed

    Ponce, R; Armstrong, K; Andrews, K; Hensler, J; Waggie, K; Heffernan, J; Reynolds, T; Rogge, M

    2005-01-01

    Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

  20. 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.

  1. Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization.

    PubMed

    Hilty, Matthias Peter; Müller, Andrea; Flück, Daniela; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Auinger, Katja; Lundby, Carsten; Maggiorini, Marco

    2016-12-01

    Matthias Peter Hilty, Andrea Mueller, Daniela Flück, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Katja Auinger, Carsten Lundby, and Marco Maggiorini. Effect of increased blood flow on the pulmonary circulation before and during high altitude acclimatization. High Alt Med Biol. 17:305-314, 2016.-Introduction and Methods: Acute exposure to high altitude increases pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR). The evolution of Ppa and PVR with continuous hypoxic exposure remains, however, elusive. To test the hypothesis that altitude exposure leads to a persistent elevation in Ppa and PVR throughout acclimatization in seven healthy male subjects, echocardiography was performed at sea level (SL; 488 m) weekly during a 4-week sojourn at 3454 m (HA1-HA4) and upon return (SL2). Pulmonary artery catheterization and bilateral thigh cuff release maneuver were performed at SL and HA3 to study the properties of pulmonary circulation after 3 weeks of acclimatization. Pulmonary artery catheter determined that systolic Ppa (mean ± SEM) was increased from 20 ± 1 at SL to 27 ± 2 mmHg at HA3 (p < 0.01). Echocardiography assessed that systolic Ppa remained equally increased throughout acclimatization (26 ± 2, 25 ± 2, 25 ± 2, and 24 ± 2 mmHg at HA1-HA4; p = 0.93) and returned to baseline upon return (17 ± 2, 18 ± 1 mmHg at SL, SL2; p = 0.3). The same was shown for PVR. Right heart function remained unaffected. Thigh cuff release maneuvers at SL and HA3 resulted in similar increase in cardiac output (2.5 ± 0.5 and 2.2 ± 0.4 L/min; p = 0.61) without affecting mean Ppa. Prolonged altitude exposure leads to a persistent increase in Ppa and PVR without affecting right heart function and is fully reversible within 1 week after return to SL. The thigh cuff release maneuver-induced increase in cardiac output suggests a preserved ability of pulmonary circulation to cope with

  2. Microtube device for selectin-mediated capture of viable circulating tumor cells from blood.

    PubMed

    Hughes, Andrew D; Mattison, Jeff; Western, Laura T; Powderly, John D; Greene, Bryan T; King, Michael R

    2012-05-01

    Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage. We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer. Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20-704 viable CTCs per 3.75-mL sample, achieving purities of 18%-80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading. The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.

  3. 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

  4. High Levels of Peripheral Blood Circulating Plasma Cells as a Specific Risk Factor for Progression of Smoldering Multiple Myeloma

    PubMed Central

    Bianchi, Giada; Kyle, Robert A.; Larson, Dirk R.; Witzig, Thomas E.; Kumar, Shaji; Dispenzieri, Angela; Morice, William G.; Rajkumar, S. Vincent

    2012-01-01

    Smoldering multiple myeloma (SMM) carries a 50% risk of progression to multiple myeloma (MM) or related malignancy within the first 5 years following diagnosis. The goal of this study was to determine if high levels of circulating plasma cells (PCs) are predictive of SMM transformation within the first 2–3 years from diagnosis. Ninety-one patients diagnosed with SMM at Mayo Clinic from January 1994 through January 2007 who had testing for circulating PCs using an immunofluorescent assay and adequate follow up to ascertain disease progression, were studied. High level of circulating PCs was defined as absolute peripheral blood PCs >5000 ×106/L and/or > 5% cytoplasmic immunoglobulin (Ig) positive PCs per 100 peripheral blood mononuclear cells. Patients with high circulating PCs (14 of 91 patients, 15%) were significantly more likely to progress to active disease within 2 years compared with patients without high circulating PCs, 71% versus 25%, respectively, P=0.001. Corresponding rates for progression within 3 years were 86% versus 35%, respectively, P<0.001. Overall survival (OS) after both SMM diagnosis and MM diagnosis was also significantly different. High levels of circulating PCs identify SMM patients with an elevated risk of progression within the first 2 to 3 years following diagnosis. PMID:22902364

  5. High levels of peripheral blood circulating plasma cells as a specific risk factor for progression of smoldering multiple myeloma.

    PubMed

    Bianchi, G; Kyle, R A; Larson, D R; Witzig, T E; Kumar, S; Dispenzieri, A; Morice, W G; Rajkumar, S V

    2013-03-01

    Smoldering multiple myeloma (SMM) carries a 50% risk of progression to multiple myeloma (MM) or related malignancy within the first 5 years following diagnosis. The goal of this study was to determine if high levels of circulating plasma cells (PCs) are predictive of SMM transformation within the first 2-3 years from diagnosis. Ninety-one patients diagnosed with SMM at Mayo Clinic from January 1994 through January 2007, who had testing for circulating PCs using an immunofluorescent assay and adequate follow-up to ascertain disease progression, were studied. High level of circulating PCs was defined as absolute peripheral blood PCs >5 × 10(6)/l and/or >5% PCs per 100 cytoplasmic immunoglobulin (Ig)-positive peripheral blood mononuclear cells. Patients with high circulating PCs (14 of 91 patients, 15%) were significantly more likely to progress to active disease within 2 years compared with patients without high circulating PCs, 71% versus 24%, respectively, P=0.001. Corresponding rates for progression within 3 years were 86% versus 34%, respectively, P<0.001. Overall survival (OS) after both SMM diagnosis and MM diagnosis was also significantly different. High levels of circulating PCs identify SMM patients with an elevated risk of progression within the first 2-3 years following diagnosis.

  6. 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.

  7. 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

  8. Cell-sheet Therapy With Omentopexy Promotes Arteriogenesis and Improves Coronary Circulation Physiology in Failing Heart

    PubMed Central

    Kainuma, Satoshi; Miyagawa, Shigeru; Fukushima, Satsuki; Pearson, James; Chen, Yi Ching; Saito, Atsuhiro; Harada, Akima; Shiozaki, Motoko; Iseoka, Hiroko; Watabe, Tadashi; Watabe, Hiroshi; Horitsugi, Genki; Ishibashi, Mana; Ikeda, Hayato; Tsuchimochi, Hirotsugu; Sonobe, Takashi; Fujii, Yutaka; Naito, Hisamichi; Umetani, Keiji; Shimizu, Tatsuya; Okano, Teruo; Kobayashi, Eiji; Daimon, Takashi; Ueno, Takayoshi; Kuratani, Toru; Toda, Koichi; Takakura, Nobuyuki; Hatazawa, Jun; Shirai, Mikiyasu; Sawa, Yoshiki

    2015-01-01

    Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31+/lectin+) and structurally (CD31+/α-SMA+) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial 13N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart. PMID:25421595

  9. 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.

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. 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.

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

    USDA-ARS?s Scientific Manuscript database

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

    PubMed

    Scharlach, Constantin; Warmuth, Carsten; Schellenberger, Eyk

    2015-11-01

    Blood circulation is an important determinant of the biodistribution of superparamagnetic iron oxide nanoparticles. Here we present a magnetic resonance imaging (MRI) technique based on the use of ultrafast echo times (UTE) for the noninvasive determination of blood half-lives at high particle concentrations, when conventional pulse sequences fail to produce a useful MR signal. Four differently coated iron oxide nanoparticles were administered intravenously at a dose of 500 μmol Fe/kg bodyweight and UTE images of C57BL/6 mice were acquired on a 1-T ICON scanner (Bruker). T2* relaxometry was done by acquiring UTE images with echo times of 0.1, 0.8 and 1.6 ms. Blood circulation time was then determined by fitting an exponential curve to the time course of the measured relaxation rates. Circulation time was shortest for particles coated with malic acid (t1/2=23 min) and longest for particles coated with tartaric acid (t1/2=63 min). UTE-based T2* relaxometry allows noninvasive determination of blood circulation time and is especially useful when high particle concentrations are present. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.…

  17. Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood

    USDA-ARS?s Scientific Manuscript database

    The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma gene transcripts that were common to 9 term pregnant women and their newborns but absent or reduced in...

  18. 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

  19. Heat dissipation by blood circulation and airway tissue heat absorption in a canine model of inhalational thermal injury.

    PubMed

    Wan, Jiangbo; Zhang, Guoan; Qiu, Yuxuan; Wen, Chunquan; Fu, Tairan

    2016-05-01

    This study aimed to further explore heat dissipation by blood circulation and airway tissue heat absorption in an inhalational thermal injury model. Twelve adult male Beagle dogs were divided into four groups to inhale heated air for 10min: the control group, group I (100.5°C), group II (161.5°C), and group III (218°C). The relative humidity and temperature of the inhaled heated air were measured in the heating tube and trachea, as were blood temperatures and flow velocities in both common jugular veins. Formulas were used to calculate the total heat quantity reduction of the heated air, heat dissipation by the blood, and airway tissue heat absorption. The blood temperatures of both the common jugular veins increased by 0.29°C±0.07°C to 2.96°C±0.24°C and the mean blood flow volume after injury induction was about 1.30-1.74 times greater than before injury induction. The proportions of heat dissipated by the blood and airway tissue heat absorption were 68.92%±14.88% and 31.13%±14.87%, respectively. The heat dissipating ability of the blood circulation was demonstrated and improved upon along with tissue heat absorption owing to increased regional blood flow. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  20. 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

  1. Manual Lymphatic Drainage in Blood Circulation of Upper Limb With Lymphedema After Breast Cancer Surgery.

    PubMed

    Guerero, Raquel Michelini; das Neves, Lais Mara Siqueira; Guirro, Rinaldo Roberto de Jesus; Guirro, Elaine Caldeira de Oliveira

    2017-05-01

    The purpose of this study was to assess blood flow after manual lymphatic drainage (MLD) in women who had received surgery for breast cancer and had post-axillary lymphadenectomy lymphedema. Sixteen volunteers (mean age 64 ± 11.44 years) were divided into 2 groups. Those in group 1 received MLD without upper limb elevation, and those in group 2 received MLD with elevation of 30° of the upper limb. Blood flow velocity of the brachial vein and artery were measured using Doppler ultrasound before, immediately after, and 30 minutes after MLD, with and without 30° of upper limb elevation as defined by a random crossover design and an interval (washout) of 7 days. Comparison of data before and after MLD was evaluated by the Friedman test. There was a significant increase of blood flow velocity in the brachial vein after the therapeutic procedure with upper limb elevation. However, after 30 minutes the data returned to the pretreatment value. This preliminary study indicated that MLD promoted increased brachial vein velocity flow in the short term. Copyright © 2017. Published by Elsevier Inc.

  2. [Clinical research on supplementing Qi and activating blood circulation herbs on lung protection in acute lung injury ventilation patients].

    PubMed

    Li, Min; Yang, Ming-hui; Dou, Yong-qi; Liu, Yi

    2014-11-01

    To study the supplementing Qi and activating blood circulation herbs on lung protection in acute lung injury (ALI) ventilation patients. 67 cases of ALI patients were enrolled and randomly divided into two groups. Routine treatment was for 32 cases of control group while treatment with adding supplementing Qi and activating blood circulation herbs was for 35 cases of treatment group, by 60 mL per time for 14 consecutive days with each day three times. Hemodynamics, changes of arterial blood gas, assay of pdymorphonuclears (PMN) value and the image of bronchoscopes between two groups in T0, T3, T7 and T14 were compared. PMN, HR, SVR, PaO2 , PO2/FiO2 and pH of treatment group were significantly improved compared with control group during T0, T3, T7 and T14 (P <0. 05). The compared differences were remarkable on hemodynamics, changes of arterial blood gas and assay of PMN value between treatment group and control group. The image of bronchoscopes in treatment group was improved significantly. The intervention of supplementing Qi and activating blood circulation herbs can effectively protect the lung function from ALI patients who received ventilation.

  3. 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.

  4. 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

  5. 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

  6. Angiogenic conditioning of peripheral blood mononuclear cells promotes fracture healing

    PubMed Central

    Mifuji, K.; Kamei, N.; Tanaka, R.; Arita, K.; Mizuno, H.; Asahara, T.; Adachi, N.; Ochi, M.

    2017-01-01

    Objectives The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing. Methods Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium in vitro. In order to evaluate the therapeutic potential of QQMNCs, cells were transplanted into an immunodeficient rat femur nonunion model. The rats were randomised into three groups: control; PBMNCs; and QQMNCs. The fracture healing was evaluated radiographically and histologically. Results The total number of PBMNCs was decreased after QQ-culture, however, the number of CD34+ and CD206+ cells were found to have increased as assessed by flow cytometry analysis. In addition, gene expression of angiogenic factors was upregulated in QQMNCs. In the animal model, the rate of bone union was higher in the QQMNC group than in the other groups. Radiographic scores and bone volume were significantly associated with the enhancement of angiogenesis in the QQMNC group. Conclusion We have demonstrated that QQMNCs have superior potential to accelerate fracture healing compared with PBMNCs. The QQMNCs could be a promising option for fracture nonunion. Cite this article: K. Mifuji, M. Ishikawa, N. Kamei, R. Tanaka, K. Arita, H. Mizuno, T. Asahara, N. Adachi, M. Ochi. Angiogenic conditioning of peripheral blood mononuclear cells promotes fracture healing. Bone Joint Res 2017;6: 489–498. DOI: 10.1302/2046-3758.68.BJR-2016-0338.R1. PMID:28835445

  7. Optimized siRNA-PEG Conjugates for Extended Blood Circulation and Reduced Urine Excretion in Mice

    PubMed Central

    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. PMID:23471415

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Ligustrazine improves blood circulation by suppressing Platelet activation in a rat model of allergic asthma.

    PubMed

    Wang, Yajuan; Zhu, Huizhi; Tong, Jiabing; Li, Zegeng

    2016-07-01

    Chuan-xiong (Ligusticum wallichii) is a traditional herbal medicine in Eastern Asia, but the effect of its active component ligustrazine remains unclear. We explored its effect and possible mechanism in a well-characterized rat model of allergic asthma. Ligustrazine suppressed bronchial hyper-responsiveness to methacholine, and suppressed lung inflammation in asthmatic rats. Ligustrazine exhibited potent immuno-modulatory and anti-inflammatory effects: it suppressed lymphocyte and eosinophil mobilization, and reduced cytokine IL-5 and IL-13 production significantly in lung tissues from asthmatic rats (P<0.05). Further histological examinations clearly demonstrated that ligustrazine improved blood circulation and ameliorated platelet activation, aggregation and adhesion, which induced sustained infiltration and activation of various inflammatory cells, including lymphocytes and eosinophils, followed by synthesis and release of a variety of pro-inflammatory mediators and cytokines. The present study suggests that ligustrazine is a potent agent for the treatment of allergic asthma due to its strong anti-inflammatory and immuno-modulatory properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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.

  14. 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.

  15. 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.

  16. Impact of negative affectivity and trait forgiveness on aortic blood pressure and coronary circulation.

    PubMed

    Sanchez-Gonzalez, Marcos A; May, Ross W; Koutnik, Andrew P; Fincham, Frank D

    2015-02-01

    Prior research suggests that negative affectivity (NA) may have a direct adverse effect on coronary circulation, whereas forgiveness may provide cardioprotection. This study examined whether NA and forgiveness were independently related to aortic hemodynamics and the subendocardial viability index (SVI), a marker of coronary perfusion. A sample of 131 adults (M = 21.11 years, SD = 2.52) were evaluated for NA (depression, anxiety, and anger symptoms) and forgiveness (Tendency to Forgive Scale; TTF). Aortic hemodynamic parameters via applanation tonometry were assessed at rest and during sympathostimulation (cold pressor test; CPT). Hierarchical multiple regression analyses of resting values showed that NA was related to higher aortic blood pressure (ABP) and lower SVI. After controlling for demographics and for NA, TTF scores were significantly associated with decreased ABP, but increased SVI. CPT changes from baseline indicated that, after controlling for demographics and NA, TTF scores were significantly associated with SVI. Results indicate that NA significantly predicts ABP and decreased SVI. Conversely, forgiveness seems to provide cardioprotection by evoking decreased ABP while improving SVI. © 2014 Society for Psychophysiological Research.

  17. 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

  18. Citrullination of CXCL8 increases this chemokine’s ability to mobilize neutrophils into the blood circulation

    PubMed Central

    Loos, Tamara; Opdenakker, Ghislain; Van Damme, Jo; Proost, Paul

    2009-01-01

    Background During the first line defense of an infected host, circulating neutrophils invade the inflamed tissue, whereas mature neutrophils from the bone marrow pool migrate into the blood circulation and from there reinforce tissue infiltration. The CXC chemokine CXCL8, also know as interleukin-8, is a potent attractant of neutrophils. Recently, we discovered a new natural post-translational modification of CXCL8, i.e. the deimination of arginine into citrulline by peptidylarginine deiminases. Design and Methods The ability to provoke leukocytosis was assessed by intravenous administration of citrullinated CXCL8 in rabbits. Adsorption of citrullinated CXCL8 to the Duffy antigen/receptor for chemokines on human or rabbit erythrocytes was evaluated using a competitive binding assay. Finally, surface expression of adhesion molecules was studied after stimulating neutrophils with citrullinated CXCL8. Results Citrullination of CXCL8 significantly increased this chemokine’s ability to recruit neutrophils into the blood circulation. In addition, the competitive binding properties of CXCL8 for the Duffy antigen/receptor for chemokines were impaired upon citrullination. Since the Duffy antigen/receptor for chemokines is an important scavenging receptor for CXCL8 in the blood stream, citrullination may delay CXCL8 clearance from the circulation. Furthermore, the shedding of CD62L (L-selectin) and the upregulation of CD11b (β2-integrin) protein expression on CXCL8-induced neutrophils were improved by deimination of CXCL8, possibly contributing to the neutrophil egress from the bone marrow. Conversely, surface expression of CD15, the neutrophilic ligand of endothelial selectins, was equally well upregulated by intact and citrullinated CXCL8. Conclusions These data show that citrullination of CXCL8 enhances leukocytosis, possibly through impaired chemokine clearance from the blood circulation and prolonged presentation to the bone marrow. PMID:19608678

  19. Rapid isolation of viable circulating tumor cells from patient blood samples.

    PubMed

    Hughes, Andrew D; Mattison, Jeff; Powderly, John D; Greene, Bryan T; King, Michael R

    2012-06-15

    Circulating tumor cells (CTC) are cells that disseminate from a primary tumor throughout the circulatory system and that can ultimately form secondary tumors at distant sites. CTC count can be used to follow disease progression based on the correlation between CTC concentration in blood and disease severity. As a treatment tool, CTC could be studied in the laboratory to develop personalized therapies. To this end, CTC isolation must cause no cellular damage, and contamination by other cell types, particularly leukocytes, must be avoided as much as possible. Many of the current techniques, including the sole FDA-approved device for CTC enumeration, destroy CTC as part of the isolation process (for more information see Ref. 2). A microfluidic device to capture viable CTC is described, consisting of a surface functionalized with E-selectin glycoprotein in addition to antibodies against epithelial markers. To enhance device performance a nanoparticle coating was applied consisting of halloysite nanotubes, an aluminosilicate nanoparticle harvested from clay. The E-selectin molecules provide a means to capture fast moving CTC that are pumped through the device, lending an advantage over alternative microfluidic devices wherein longer processing times are necessary to provide target cells with sufficient time to interact with a surface. The antibodies to epithelial targets provide CTC-specificity to the device, as well as provide a readily adjustable parameter to tune isolation. Finally, the halloysite nanotube coating allows significantly enhanced isolation compared to other techniques by helping to capture fast moving cells, providing increased surface area for protein adsorption, and repelling contaminating leukocytes. This device is produced by a straightforward technique using off-the-shelf materials, and has been successfully used to capture cancer cells from the blood of metastatic cancer patients. Captured cells are maintained for up to 15 days in culture

  20. Rapid Isolation of Viable Circulating Tumor Cells from Patient Blood Samples

    PubMed Central

    Hughes, Andrew D.; Mattison, Jeff; Powderly, John D.; Greene, Bryan T.; King, Michael R.

    2012-01-01

    Circulating tumor cells (CTC) are cells that disseminate from a primary tumor throughout the circulatory system and that can ultimately form secondary tumors at distant sites. CTC count can be used to follow disease progression based on the correlation between CTC concentration in blood and disease severity1. As a treatment tool, CTC could be studied in the laboratory to develop personalized therapies. To this end, CTC isolation must cause no cellular damage, and contamination by other cell types, particularly leukocytes, must be avoided as much as possible2. Many of the current techniques, including the sole FDA-approved device for CTC enumeration, destroy CTC as part of the isolation process (for more information see Ref. 2). A microfluidic device to capture viable CTC is described, consisting of a surface functionalized with E-selectin glycoprotein in addition to antibodies against epithelial markers3. To enhance device performance a nanoparticle coating was applied consisting of halloysite nanotubes, an aluminosilicate nanoparticle harvested from clay4. The E-selectin molecules provide a means to capture fast moving CTC that are pumped through the device, lending an advantage over alternative microfluidic devices wherein longer processing times are necessary to provide target cells with sufficient time to interact with a surface. The antibodies to epithelial targets provide CTC-specificity to the device, as well as provide a readily adjustable parameter to tune isolation. Finally, the halloysite nanotube coating allows significantly enhanced isolation compared to other techniques by helping to capture fast moving cells, providing increased surface area for protein adsorption, and repelling contaminating leukocytes3,4. This device is produced by a straightforward technique using off-the-shelf materials, and has been successfully used to capture cancer cells from the blood of metastatic cancer patients. Captured cells are maintained for up to 15 days in culture

  1. 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.

  2. 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.

  3. DNA hypomethylation of CBS promoter induced by folate deficiency is a potential noninvasive circulating biomarker for colorectal adenocarcinomas.

    PubMed

    Xue, Geng; Lu, Chao-Jing; Pan, Shu-Jun; Zhang, Yin-Ling; Miao, Hui; Shan, Shi; Zhu, Xiao-Ting; Zhang, Yi

    2017-08-01

    Aberrant DNA methylation patterns, which induced by folate deficiency, play important roles in tumorigenesis of colorectal cancer (CRC). Some DNA methylation alterations can also be detected in cell-free DNA (cfDNA) of patients' plasma, making cfDNA an ideal noninvasive circulating biomarker. However, exact DNA methylation alterations induced by folate deficiency in tumorigenesis of CRC and exact potential circulating cfDNA methylation biomarker are still unclear. Therefore, DNA methylation patterns of the normal human colon mucosal epithelial cell line (NCM460), cultured with normal or low folate content, were screened and the DNA hypomethylation of cystathionine-beta-synthase (CBS) promoter was further validated in vitro and vivo. Then, the correlation analysis between folate level, DNA methylation alteration in promoter and expression of CBS was carried out in vitro and vivo. Further, the methylation patterns of CBS promoter in plasma cfDNA were detected and statistically correlated with pathological parameters and clinical outcome. Our study showed that DNA hypomethylation in CBS promoter, induced by folate deficiency, would lead to up-regulation of CBS both in vitro and vivo. Patients with cfDNA hypomethylation of CBS promoter in plasma were correlated with high tumor stage and poor clinical outcome. In addition, cfDNA hypomethylation of CBS promoter in plasma was shown to be an independent prognostic factor for recurrence and cancer-related death in CRC. Our results indicated that DNA hypomethylation of CBS promoter induced by folate deficiency could serve as a potential noninvasive circulating biomarker and may be helpful in developing more effective prognostic markers for CRC.

  4. The effects of a fixed combination of 0.5% timolol and 1% dorzolamide on optic nerve head blood circulation.

    PubMed

    Ohguro, Ikuyo; Ohguro, Hiroshi

    2012-08-01

    The purpose of the present study is to evaluate the effects of a fixed combination of 0.5% timolol maleate (TM) and 1% dorzolamide hydrochloride (DZ) (FCTD(1%)) on optic nerve head (ONH) blood circulation. A drop of 0.5% TM, 1% DZ, or FCTD(1%) was topically administered to the right eyes of 15 healthy Japanese subjects, and a drop of saline was likewise administrated to their left eyes. Systemic blood pressure, heart rates (HRs), intraocular pressures (IOPs), ocular perfusion pressures, and blood circulation by a laser speckle flowgraphy at the ONH were measured before administration, and again at 1.5 and 6 h afterward. FCTD(1%) caused a significant increase in ONH blood circulation 6 h after the administration, while 0.5% TM and 1% DZ had no significant effect. The IOPs were significantly decreased in 0.5% TM (P<0.01) and FCTD(1%) (P<0.05) when compared with the saline-treated eyes at 1.5 and 6 h after administration, while 1% DZ did not show a statistically significant decrease. There were no significant changes in other systemic parameters except for a significant transient decrease in the HRs observed in 0.5% TM (P<0.01) when compared with the baseline at 1.5 h after the administration. Our current results suggest that FCTD(1%) caused a significant increase in ocular blood circulation on the ONH in healthy Japanese subjects, presumably by a synergistic effect of 0.5% TM and 1% DZ, although neither 0.5% TM nor 1% DZ on their own had a significant effect.

  5. [Alterations in blood circulation of vesicourethral segment in men with neurogenic and non-neurogenic lower urinary tract symptoms].

    PubMed

    Alayev, Yu G; Esilevskiy, Yu M; Shmidt, T E; Demidko, Yu L; Fiev, D N; Kazantsev, K Yu

    2016-12-01

    To specify the pathogenetic link between blood supply of the bladder neck and lower urinary tract symptoms (LUTS). The study involved 78 men aged 26 to 50 years, including 19 patients with multiple sclerosis (MS) and LUTS, 29 patients with chronic prostatitis category IIIB with LUTS and 30 patients with chronic prostatitis category IIIB without LUTS (control group). All the patients underwent Doppler ultrasonography of prostatic arteries and selective study of blood flow in the neck of the bladder. Pharmacological test using combinations of 1-blockers (1-AB) with m-anticholinergics (m-CB) and phosphodiesterase type 5 inhibitors (PDEI-5). The changes in the blood circulation of VUS were found to correlate with LUTS. The response of blood flow depended not only on the type of pharmacological agents, but also on the degree of vascular changes and neurological deficit in VUS. The findings of VUS vascular pharmacological tests with PDEI-5 and 1-AB + m-CB were comparable in chronic prostatitis with non-neurogenic LUTS and in MS with neurogenic LUTS. Vascular reaction in VUS depends on the presence of neurological deficit. The combination of (1-AB+ m-CB) increases the blood circulation of the bladder neck and prostate and reduces the LUTS. PDEI-5 reduces LUTS due to the positive effect on the blood circulation of the prostate and VUS. Circulatory abnormalities (=hypoxia) in VUS is an important pathogenetic mechanism of neurogenic and non-neurogenic LUTS and the way to compensate them using a combination of (1-AB+ m-CB) or PDEI-5. Therefore, one of the mechanisms of LUTS is associated with impaired blood flow in the bladder neck and VUS.

  6. Liberation of a bradykinin-like substance in the circulating blood of dogs by trypsin, chymotrypsin and nagarse

    PubMed Central

    Ferreira, S. H.; Silva, M. Rocha E

    1969-01-01

    1. Using the blood-bathed organ technique with cat jejunum as the test organ, it was shown that kinin was regularly released by infusions of trypsin, chymotrypsin and nagarse into the blood superfusing the tissue or into the jugular vein of dogs. 2. Intravenous injections of the three enzymes, in doses which did not change plasma bradykininogen (BKG) level, induced generation of kinin in the circulating blood. 3. Nagarse in kinin-liberating concentrations did not liberate angiotensin in the circulating blood. 4. The responses of the cat jejunum strip, and the systemic hypotension induced by the three enzymes, were enhanced by treatment of the dog with a bradykinin potentiator. 5. Injection of the enzymes in the blood perfused hind leg of the dog caused a fall in the vascular resistance. In this preparation, bradykinin potentiating factor (BPF) potentiated trypsin, but not the effects of chymotrypsin and nagarse injections. 6. It is suggested that the blood pressure lowering effect of low doses of trypsin is due mainly to kinin release. Chymotrypsin and nagarse, in addition to having a direct action on the vascular smooth muscles, also have indirect hypotensive effects due to the liberation of kinin. PMID:5789813

  7. Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.

    PubMed

    Bailey, Damian M; Rasmussen, Peter; Overgaard, Morten; Evans, Kevin A; Bohm, Aske M; Seifert, Thomas; Brassard, Patrice; Zaar, Morten; Nielsen, Henning B; Raven, Peter B; Secher, Niels H

    2017-01-10

    The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish their relative contribution in vivo, we quantified arterial-venous concentration gradients across the human cerebral and femoral circulation at rest and during exercise, an ideal model system characterized by physiological extremes of O2 tension and blood flow. Ten healthy participants (5 men, 5 women) aged 24±4 (mean±SD) years old were randomly assigned to a normoxic (21% O2) and hypoxic (10% O2) trial with measurements performed at rest and after 30 minutes of cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled simultaneously from the brachial artery and internal jugular and femoral veins with plasma and RBC nitric oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow was determined by transcranial Doppler ultrasound (cerebral blood flow) and constant infusion thermodilution (femoral blood flow) with net exchange calculated via the Fick principle. Hypoxia was associated with a mild increase in both cerebral blood flow and femoral blood flow (P<0.05 versus normoxia) with further, more pronounced increases observed in femoral blood flow during exercise (P<0.05 versus rest) in proportion to the reduction in RBC oxygenation (r=0.680-0.769, P<0.001). Plasma gradients reflecting consumption (arterial>venous; P<0.05) were accompanied by RBC iron nitrosylhemoglobin formation (venous>arterial; P<0.05) at rest in normoxia, during hypoxia (P<0.05 versus normoxia), and especially during exercise (P<0.05 versus rest), with the most pronounced gradients observed across the bioenergetically more active, hypoxemic, and acidotic femoral circulation (P<0.05 versus cerebral). In contrast, we failed

  8. [Effect of Chinese herbal medicine with Supplement Qi and Activating Blood Circulation on tubular reabsorption function of diabetic nephropathy rats].

    PubMed

    Yin, Juan-Juan; Yang, Ye; Wang, Qing-Bao; Li, Yun; Yin, Deng-Ke

    2013-06-01

    To investigate the effect of Chinese herbal medicine with Supplement Qi and Activating Blood Circulation (huangqi and danshen) on urinary protein, kidney function and tubular reabsorption of diabetic nephropathy rats. SD rats were randomly divided into a nondiabetic control group (normal group) and three groups in which diabetes were induced by a single intraperitoneal injection of freshly prepared streptozotocin( STZ,55 mg/kg body weight). Then the diabetes rats were randomly assigned to three groups: diabetic model group, Supplement Qi and Activating Blood Circulation traditional Chinese medicine group (huangqi and danshen group) and Gliquidone group (as a reference hypoglycemic drug). Each group was treated with corresponding drugs for 6 weeks. At the end of the study, the rats from each group were injected with FITC-labeled BSA through tail vein. The 24 h urinary protein excretion were measured and blood was collected for measuring plasma glucose levels, serum creatinine (Cr), blood urea nitrogen (BUN), triglyceride (TG) and total cholesterol (T-CHO). Renal tissue was used to measure the level of LPO,SOD,GSH-Px and AGEs and Paraffin-embedded sections were stained with HE, PAS and immunohistochemistry. The plasma glucose, the 24 h urinary protein excretion, the levels of serum Cr, BUN, TG and T-CHO in STZ-induced diabetic rats were higher than those of nondiabetic rats. Diabetic rats showed significantly increase in LPO and AGEs (P < 0.01) and decrease in antioxidant enzyme activity (both GSH-Px and SOD) (P < 0.05) as compared with non-diabetic control rats. Treatment with the Supplement Qi and Activating Blood Circulation traditional Chinese medicine for 6 weeks in diabetic rats significantly reduced the 24 h urinary protein excretion compared with model control (P < 0.01), and markedly decreased the levels of serum Cr,BUN,TG and T-CHO as compared with those of diabetic rat (P < 0.05). The levels of LPO and AGEs were decreased and the activity of GSH-Px was

  9. [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.

  10. [The influence of cardiosurgical intervention type and conditions of artificial blood circulation of perioperative dynamics of cardiac biomarkers].

    PubMed

    Dement'eva, I I; Morozov, Iu A; Charnaia, M A

    2013-01-01

    125 patients after cardiac surgery operated on with the use of artificial blood circulation (ABC) were followed-up. Blood levels of cardiac protein, binding aliphatic acids and troponin 1 and 3 days after the operation were registered. The study showed that aorta clamping more then 90 minutes and hypothermic perfusion regimen influence cardiomyocites negatively. The state of "surgical trauma" and reperfusional myocardium damage was approximately the same during aortic surgery, myocardium revascularization with the use of aortic clamping and cardioplegia, and correction of the acquired heart disease, according to the dynamics of the studied proteins in blood. The minimal blood level of cardiac protein, binding aliphatic acids after coronary by-pass surgery on the working heart witnesses about negative influence of crystalloid hypothermic cardioplegia on coronary microcirculation.

  11. [Study on material basis of essential oil from Yin Teng Gu Bi Kang prescription on activating blood circulation].

    PubMed

    Wang, Yuan-Qing; Yan, Jian-Ye; Gong, Li-Min; Luo, Kun; Li, Shun-Xiang; Yang, Yan-Tao; Xie, Yu

    2014-08-01

    To explore the component difference of the serum containing essential oil from Yin Teng Gu Bi Kang prescription in pathologic and physiologic rat models, and to reveal the material basis of its efficacy of activating blood circulation. The essential oils were obtained by CO2 supercritical fluid extraction and the ingredients of the essential oils in vitro and in vivo (under physiological and pathological status) were analyzed by GC-MS to compare differences of the essential oil under physiological and pathological status in rats. 32 components were identified with the main components of Z-ligustilide (39.23%) and d-limonene (21.7%) in the essential oil. In vivo analysis on the essential oil indicated that 16 components were identified, 7 existed originally in essential oil and 9 were metabolites under physiological status; while 22 components were identified, 10 existed originally in essential oil and 12 were metabolites under pathological status (acute blood stasis). There were 7 common prototypes and 8 common metabolites under different physiological status. The absorption and metabolism of essential oils were affected by blood stasis and the compounds migrating to blood may be the effective substance in activating blood circulation.

  12. [Observation on clinical efficacy of activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility].

    PubMed

    Fan, Xiao-Di; Ma, Kun; Shan, Jing; Jin, Xuan-Ting

    2013-01-01

    To discuss the clinical efficacy of the activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility. Eighty-six cases were randomly divided into two groups: the treatment group and the control group. The treatment group is administered with the activating renal blood circulation and ovarian stimulation formula (composed of 15 g Cuscutae Semen, 15 g Dipsaci Asperoidis Radix, 15 g Lycii Fructus, 15 g Spatholobi Caulis, 10 g Ligustri Lucidi Fructus, 15 g Lycopi Herba, 10 g Typhae Polleu, 10 g Angelicae Sinensis Radix, 15 g Cyathulae Radix etc.), whereas the control group was given clomiphene. The treatment group showed a pregnancy rate of 58.14%, with an ovulation rate of 68.6%. While the control group showed a pregnancy rate of 36.67%, with an ovulation rate of 70%. The comparison between the two groups showed that the activating renal blood circulation and ovarian stimulation formula was significantly different from clomiphene in statistical analysis (P < 0.05), without notable difference in the ovulation rate. Before and after the treatment, there is no significant difference in diameter of dominant follicles between the two groups, with remarkable difference in endometrium (P < 0.05).

  13. Red blood cell membrane fragments but not intact red blood cells promote calcium oxalate monohydrate crystal growth and aggregation.

    PubMed

    Chutipongtanate, Somchai; Thongboonkerd, Visith

    2010-08-01

    Cell membranes are thought to promote calcium oxalate kidney stone formation but to our knowledge the modulating effect of red blood cell membranes on calcium oxalate crystals has not been previously investigated. Thus, we examined the effects of red blood cell membrane fragments on calcium oxalate monohydrate and calcium oxalate dihydrate crystal growth and aggregation. Calcium oxalate monohydrate and calcium oxalate dihydrate crystals were treated with red blood cell membrane fragments or intact red blood cells from a healthy donor. Phase contrast microscopy was performed to evaluate crystal morphology and aggregation. We used ImageMaster 2D Platinum software to evaluate crystal size and spectrophotometric oxalate depletion assay to monitor crystal growth. Red blood cell membrane fragments had significant promoting activity on calcium oxalate monohydrate crystal growth with an approximately 75% increase in size and aggregation with an approximately 2.5-fold increase in aggregate number compared to the control without membrane fragments or cells. Approximately 50% of calcium oxalate monohydrate crystals were adhered by red blood cell membrane fragments. Intact red blood cells had no significant effect on calcium oxalate monohydrate crystal growth or aggregation but they could transform calcium oxalate monohydrate to calcium oxalate dihydrate crystals. Red blood cell membrane fragments and intact red blood cells had no effect on calcium oxalate dihydrate crystals. The promoting activity of red blood cell membrane fragments on calcium oxalate monohydrate crystal growth was successfully confirmed by spectrophotometric oxalate depletion assay. To our knowledge our data provide the first direct evidence that red blood cell membrane fragments are a promoting factor for calcium oxalate monohydrate crystal growth and aggregation. Thus, they may aggravate calcium oxalate stone formation. Copyright (c) 2010 American Urological Association Education and Research, Inc

  14. 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

  15. 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.

  16. Fate of radioactive exocrine pancreatic proteins injected into the blood circulation of the rat. Tissue uptake and transepithelial excretion

    SciTech Connect

    Rohr, G.; Scheele, G.

    1983-11-01

    (/sup 35/S)methionine or (/sup 35/S)methionine-labeled exocrine pancreatic proteins were injected into the bloodstream of conscious rats. Samples of blood, urine, bile, and pancreatic juice were collected at varying intervals through 7 h. Injection of (/sup 35/S)methionine resulted in the appearance of trichloroacetic acid--soluble radioactivity ((/sup 35/S)methionine) in bile and urine within 4 min and trichloroacetic acid-insoluble radioactivity in blood, bile, and pancreatic juice after 20 min. Analysis of these body fluids by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis and fluorography indicated that rat serum, biliary, and pancreatic proteins were labeled, respectively. After the injection of (/sup 35/S)methionine-labeled pancreatic proteins, half of the trichloroacetic acid-insoluble radioactivity disappeared from the serum in 10-15 min. Radioactive proteins appeared after 5 min in urine and bile, and, over the course of the experiment, accounted for 1%-2% and 0.3%-0.5% of the injected radioactivity, respectively. The studies indicate that pancreatic proteins are removed from the blood circulation by at least three separate pathways: (a) uptake and degradation by a variety of tissues in the body (approximately 97% of injected radioactivity), (b) excretion of intact proteins into urine (1%-2%), and (c) transport of intact proteins into bile (0.3%-0.5%). Transport of exocrine pancreatic proteins from the blood circulation to pancreatic juice could not be demonstrated.

  17. Gcsf-Chr19 promotes neutrophil migration to damaged tissue through blood vessels in zebrafish.

    PubMed

    Galdames, Jorge A; Zuñiga-Traslaviña, Constanza; Reyes, Ariel E; Feijóo, Carmen G

    2014-07-01

    G-CSF is an essential cytokine that regulates proliferation and differentiation of granulocytes from hematopoietic stem and progenitor cells. In mammals G-CSF has been identified as a key factor that promotes the release of neutrophils from the bone marrow into the blood circulation. In silico analysis indicates that zebrafish has two gcsf genes, gcsf-chr12 in chromosome 12 and gcsf-chr19 in chromosome 19. Gcsf-Chr12 participates in emergency myelopoiesis, but, in contrast to its mammalian orthologue, is not involved in neutrophil migration toward damaged tissue. In turn, the function of Gcsf-Chr19 has not been examined yet. In this study, we analyzed the role of Gcsf-Chr19 in regulating neutrophil migration toward the wound. Our results indicated that during the first h after caudal fin transection, neutrophils migrate from the hematopoietic tissue toward the injury, using the extracellular matrix as a substrate. Later, between 3 and 4 h postdamage, the recruitment mainly occurs through the bloodstream, and only a few neutrophils still use the extracellular matrix to migrate. During this process, the transcriptional levels of gcsf-chr19 are considerably increased, reaching a peak 1 h postdamage. The knockdown of Gcsf-chr19 indicated that the percentage of neutrophils that reach the wound decreased after the first h postinjury, suggesting that the knockdown specifically affects neutrophils that travel to the wound through blood vessels. Together, our data provide novel information about the regulation of neutrophil migration in zebrafish, positioning Gcsf-Chr19 as a key signal during the course of an inflammatory process triggered by severe damage. Copyright © 2014 by The American Association of Immunologists, Inc.

  18. 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.

  19. Biomechanical model of the coronary blood flow and its relation to certain aspects of auxiliary circulation research

    NASA Astrophysics Data System (ADS)

    Kogan, V. A.

    1981-11-01

    Whereas under experimental conditions it is possible to investigate the responses of the self-regulatory mechanisms of the coronary circulation either with a constant load on the myocardium and variable conditions of perfusion of the coronary system [17] or vice-versa [18], in the case of balloon pulsation both these factors act togetherandin animal experiments cannot be distinguished. At the same time, their separate evaluation is important in studying the hemodynamic efficiency of the counterpulsation method. The proposed model of the biomechanics of the coronary circulation is sensitive to changes in the conditions of perfusion of the myocardium and at the same time maintains a constant value of the coronary resistance irrespective of the energy consumption of the heart. Accordingly, by comparing the results of modeling and the experimental data it is possible to estimate the contribution of the self-regulatory mechanisms of the coronary blood flow to the change in the transport functions of the coronary circulation associated with intraaortic balloon pulsation. Thus, the proposed model can be used as a tool for investigating the blood supply to the normal heart and for the partial evaluation of the hemodynamic efficiency of the intraaortic counterpulsation method.

  20. 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.

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

    NASA Astrophysics Data System (ADS)

    Chan, Iatneng

    2012-02-01

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

  2. Markers of circulating tumour cells in the peripheral blood of patients with melanoma correlate with disease recurrence and progression.

    PubMed

    Reid, A L; Millward, M; Pearce, R; Lee, M; Frank, M H; Ireland, A; Monshizadeh, L; Rai, T; Heenan, P; Medic, S; Kumarasinghe, P; Ziman, M

    2013-01-01

    Multimarker quantitative real-time polymerase chain reaction (qRT-PCR) represents an effective method for detecting circulating tumour cells in the peripheral blood of patients with melanoma. To investigate whether the phenotype of circulating melanoma cells represents a useful indicator of disease stage, recurrence and treatment efficacy.   Peripheral blood was collected from 230 patients with melanoma and 152 healthy controls over a period of 3years and 9months. Clinical data and blood samples were collected from patients with primary melanoma (early stages, 0-II, n=154) and metastatic melanoma (late stages, III-IV, n=76). Each specimen was examined by qRT-PCR analysis for the expression of five markers: MLANA, ABCB5, TGFβ2, PAX3d and MCAM.  In total, 212 of the patients with melanoma (92%) expressed markers in their peripheral blood. Two markers, MLANA and ABCB5, had the greatest prognostic value, and were identified as statistically significant among patients who experienced disease recurrence within our study period, being expressed in 45% (MLANA) and 49% (ABCB5) of patients with recurrence (P=0·001 and P=0·031, respectively). For patients administered nonsurgical treatments, MCAM expression correlated with poor treatment outcome. Circulating tumour cells were detectable at all stages of disease and long after surgical treatment, even when patients were considered disease free. Specifically, expression of ABCB5 and MLANA had significant prognostic value in inferring disease recurrence, while MCAM expression was associated with poor patient outcome after treatment, confirming multimarker qRT-PCR as a potential technique for monitoring disease status. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  3. Cell-free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer.

    PubMed

    Schwarzenbach, Heidi; Alix-Panabières, Catherine; Müller, Imke; Letang, Nicolas; Vendrell, Jean-Pierre; Rebillard, Xavier; Pantel, Klaus

    2009-02-01

    Circulating cell-free DNA in the blood of cancer patients harbors tumor-specific aberrations. Here, we investigated whether this DNA might also reflect the presence of circulating tumor cells (CTC). To identify the source of cell-free DNA in blood, plasma derived from 81 patients with prostate cancer was examined for CTCs and cell-free DNA. An epithelial immunospot assay was applied for detection of CTCs, and a PCR-based fluorescence microsatellite analysis with a panel of 14 polymorphic markers was used for detection of allelic imbalances (AI). The plasma DNA levels significantly correlated with the diagnosis subgroups of localized (stage M0, n = 69) and metastasized prostate cancer (stage M1, n = 12; P = 0.03) and with the tumor stage of these patients (P < 0.005). AI was found on cell-free DNA in plasma from 45.0% and 58.5% of M0 and M1 patients, respectively. Detection of CTCs showed that 71.0% or 92.0% of the M0 and M1 patients harbored 1 to 40 CTCs in their blood, respectively. The occurrence of CTCs correlated with tumor stage (P < 0.03) and increasing Gleason scores (P = 0.04). Notably, significant associations of the number of CTCs with the AI frequencies at the markers D8S137 (P = 0.03), D9S171 (P = 0.04), and D17S855 (P = 0.02) encoding the cytoskeletal protein dematin, the inhibitor of the cyclin-dependent kinase CDKN2/p16 and BRCA1, respectively, were observed. These findings show, for the first time, a relationship between the occurrence of CTCs and circulating tumor-associated DNA in blood, which, therefore, might become a valuable new source for monitoring metastatic progression in cancer patients.

  4. 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

  5. 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.

  6. 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.

  7. Effect of centrally administered endothelin agonists on systemic and regional blood circulation in the rat: role of sympathetic nervous system.

    PubMed

    Gulati, A; Kumar, A; Morrison, S; Shahani, B T

    1997-08-01

    The aims of the present study were to determine (1) the hypotensive and regional circulatory effects of centrally administered endothelin (ET) ETA and ETB agonists, and (2) the role of the sympathetic nervous system in the mediation of hypotensive effects due to centrally administered ET-1. The systemic haemodynamics and regional blood circulation in urethane anaesthetized rats following intracerebroventricular (i.c.v.) administration of ET-1, ET-2, SRT6b, ET-3 and SRT6c (10, 30 and 90 ng) were determined by a radioactive microsphere technique. The effect of centrally administered ET-1 on sympathetic nerve activity was also analysed. Systemic haemodynamics and regional blood circulation were determined before (baseline) and 30 min after administration of ET agonists. Cumulative administration of three doses of saline (5 microliters, i.c.v. at 30 min intervals) did not produce any significant cardiovascular effects. ET-1, ET-2 and SRT6b produced a decrease in blood pressure (51%, 47% and 41%, respectively) along with a decrease in cardiac output (58%, 60% and 45%, respectively) and stroke volume. Heart rate and total peripheral resistance were not affected. ET-1, ET-2 and SRT6b also produced a significant reduction in blood flow to the brain, kidneys, heart, portal, mesentery and pancreas, gastrointestinal tract (GIT) and musculoskeletal system. The effect of ET-2 on the cardiovascular system was less intense in comparison with ET-1 and SRT6b. Centrally administered specific ETB receptor agonists ET-3 and SRT6c did not produce any change in systemic haemodynamics and regional blood flow. Centrally administered ET-1 (90 ng) produced a significant decrease (61%) in sympathetic nerve activity 30 min after drug administration, along with a fall in blood pressure. It is concluded that centrally administered ETA agonists produce significant cardiovascular effects mediating through the sympathetic nervous system.

  8. 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.

  9. CR1-mediated ATP Release by Human Red Blood Cells Promotes CR1 Clustering and Modulates the Immune Transfer Process*

    PubMed Central

    Melhorn, Mark I.; Brodsky, Abigail S.; Estanislau, Jessica; Khoory, Joseph A.; Illigens, Ben; Hamachi, Itaru; Kurishita, Yasutaka; Fraser, Andrew D.; Nicholson-Weller, Anne; Dolmatova, Elena; Duffy, Heather S.; Ghiran, Ionita C.

    2013-01-01

    Humans and other higher primates are unique among mammals in using complement receptor 1 (CR1, CD35) on red blood cells (RBC) to ligate complement-tagged inflammatory particles (immune complexes, apoptotic/necrotic debris, and microbes) in the circulation for quiet transport to the sinusoids of spleen and liver where resident macrophages remove the particles, but allow the RBC to return unharmed to the circulation. This process is called immune-adherence clearance. In this study we found using luminometric- and fluorescence-based methods that ligation of CR1 on human RBC promotes ATP release. Our data show that CR1-mediated ATP release does not depend on Ca2+ or enzymes previously shown to mediate an increase in membrane deformability promoted by CR1 ligation. Furthermore, ATP release following CR1 ligation increases the mobility of the lipid fraction of RBC membranes, which in turn facilitates CR1 clustering, and thereby enhances the binding avidity of complement-opsonized particles to the RBC CR1. Finally, we have found that RBC-derived ATP has a stimulatory effect on phagocytosis of immune-adherent immune complexes. PMID:24022490

  10. Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation.

    PubMed

    West, John B

    2013-02-01

    In 1953 Frank Low published the first high-resolution electron micrographs of the human pulmonary blood-gas barrier. These showed that a structure only 0.3-μm thick separated the capillary blood from the alveolar gas, immediately suggesting that the barrier might be vulnerable to mechanical failure if the capillary pressure increased. However, it was 38 years before stress failure was recognized. Initially it was implicated in the pathogenesis of High Altitude Pulmonary Edema, but it was soon clear that stress failure of pulmonary capillaries is common. The vulnerability of the blood-gas barrier is a key factor in the evolution of the pulmonary circulation. As evolution progressed from the ancestors of fishes to amphibians, reptiles, and finally birds and mammals, two factors challenged the integrity of the barrier. One was the requirement for the barrier to become increasingly thin because of the greater oxygen consumption. The other was the high pulmonary capillary pressures that were inevitable before there was complete separation of the pulmonary and systemic circulations.

  11. 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

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

    PubMed

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

    2016-01-01

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

  13. 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.

  14. 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.

  15. 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

  16. Preliminary report of 48-hours Atosiban administration in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

    PubMed

    Grzesiak, Mariusz; Wilczynski, Jan

    2013-01-01

    The aims were to investigate whether there are any changes in placental and fetal circulation during Atosiban tocolysis within the first 48 hours of therapy. Detailed Doppler evaluation of placental and fetal circulation was performed prior to Atosiban administration and thereafter at 24 and 48 hours. Maternal heart rate and the pulsatility index (PI) in both uterine arteries (R-UtA, L-UtA) were assessed. Fetal heart rate (FHR), the resistance (RI) and pulsatility index (PI) of umbilical (UA) and middle cerebral artery (MCA) were measured. Additionally cerebroplacental ratio was calculated. E-wave/A-wave ratio (E/A) for atrioventricular valves, the myocardial performance index (MPI) and shortening fraction (SF) for both ventricles were calculated for both ventricles independently. To determine changes over time in all study variables analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's post hoc test was used. The effects of additional clinical covariates were checked. Maternal heart rate and blood flow in (R-UtA/L-UtA) were not altered significantly during Atosiban administration. No significant changes in FHR as well as Doppler parameters (RI, PI, PSV) in UA and MCA were recorded after 24/48 hours of tocolytic treatment. The mean values of cerebroplacental ratio (CPR) remained unaltered during treatment. Detailed evaluation of fetal cardiac function parameters (E/A, SF, MPI) calculated independently for both ventricles, revealed no significant changes over the time. To our best knowledge this study has been first evaluation of placental and fetal circulation with assessment of cardiac hemodynamic function during 48-hours administration of Atosiban. This kind of tocolysis treatment seems not to alter uterine nor fetal arterial blood flow pattern seriously. Hemodynamic cardiac activity in fetuses has remained unaffected. We cannot conclude definitely that there are absolutely no changes in the fetal hemodynamic condition due to Atosiban

  17. Elimination of Young Erythrocytes from Blood Circulation and Altered Erythropoietic Patterns during Paraquat Induced Anemic Phase in Mice

    PubMed Central

    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. PMID:24945144

  18. 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.

  19. 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

  20. [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.

  1. Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats.

    PubMed

    Tan, J S; Butterfield, D E; Voycheck, C L; Caldwell, K D; Li, J T

    1993-09-01

    The biological fate of injected foreign particles is believed to be closely related to their interactions with blood plasma proteins and cells. In order to verify this correlation, we have quantitatively measured protein adsorption and blood retention profiles in rats by using model polystyrene latex nanoparticles. The in vitro interactions of these non-biodegradable particles with plasma proteins and whole blood can be altered by modifying their surfaces with a family of amphiphilic polymeric surfactants, PEO/PPO Pluronic or Tetronic block copolymers. Protein adsorption was measured by several techniques, including photon correlation spectroscopy, centrifugation, high performance liquid chromatography and field-flow fractionation. Pluronic F108 and Tetronic 908 and 1508 copolymers (with PEO terminal block MWPEO > 5000, PPO middle block MWPPO > 3000, and HLB values > 24) were shown to be the most effective surface modifiers in reducing adsorption of plasma proteins on the particles. Minimum interaction of coated particles with whole blood was also observed by optical microscopy. The blood circulation half-life of the particles injected in rats was increased from 20 min to 13 h when the latex particles (75 nm) were precoated with these block copolymers. These results suggest that nanoparticles designed for use as injectable drugs or drug carriers should display similar surface characteristics provided by such amphiphilic surface modifiers.

  2. [Blood gas analytical study on cerebral circulation under the influence of dihydroergotoxin (author's transl)].

    PubMed

    Liesegang, J; Bock, W J; Seibert, H; Schumacher, W

    1976-01-01

    The demand for sufficient blood supply and oxygenation of cerebral tissue after brain surgery or severe head injuries requires the clinical investigation of drugs which are supposed to improve cerebral blood flow and metabolism. We have therefore used the hydrogenated derivatives of the ergotoxin components of the secale alcaloids in the post-operative and posttraumatic period of neurosurgical patients, respectively, and studied their effect on cerebral metabolism by successive analysis of blood gases in the arterial and venous blood. A significant increase of cerebral venous CO2-concentration following the administration of dihydroergotoxin in these patients in all probability is attributable to an improved O2-utilisation in the cerebral tissue.

  3. Evaluation of Streck BCT and PAXgene Stabilised Blood Collection Tubes for Cell-Free Circulating DNA Studies in Plasma.

    PubMed

    Warton, Kristina; Yuwono, Nicole L; Cowley, Mark J; McCabe, Mark J; So, Alwin; Ford, Caroline E

    2017-06-19

    Blood samples for studies of circulating DNA in disease are often collected in clinical settings where prompt processing of samples is not possible. In order to avoid problems associated with leukocyte lysis after prolonged blood storage, stabilised blood tubes have been developed containing preservatives that prevent cell lysis. We evaluated Streck BCT tubes and PAXgene ccfDNA tubes, as well as standard EDTA blood collection tubes, in terms of DNA yield and fragment size. Blood was collected in EDTA, Streck BCT or PAXgene ccfDNA tubes and stored for 1 h at 4 °C, or 4 days at room temperature. DNA was extracted using the QIAamp Circulating Nucleic Acids kit, and visualised on an agarose gel or quantitated by qPCR. Ratios of a 247-base and a 115-base amplicon of the Alu repetitive element were used to infer size distribution. While plasma DNA in EDTA tube blood samples increased by ~10- to 20-fold after 4 days of storage at room temperature, both Streck BCT tubes and PAXgene ccfDNA tubes maintained stable plasma DNA concentrations. A slight decrease in DNA yield following 1 h of blood storage at 4 °C was observed in Streck BCT and PAXgene ccfDNA tubes relative to EDTA tubes. This decrease was reversed by increasing the proteinase digest step of the DNA extraction protocol to 60 min, as recommended by Streck tube product literature. Visualisation of the extracted DNA on an agarose gel showed that after 4 days of room temperature storage, samples collected in EDTA tubes contained abundant high-molecular weight DNA, which was partially fragmented in a ladder pattern. A slight increase in high-molecular weight DNA in samples stored for 4 days at room temperature in Streck BCT tubes was also observed, but this was not reflected in a change in large and small Alu fragment ratios as measured by qPCR. Tubes containing preservative to prevent cell lysis can extend the scope for blood collection in clinical settings; however, slight differences between samples

  4. [Blood circulation and the trinity. Medical antitrinitarians Michael Servet (1511-1553) and Giorgio Biandrata (1515-1588)].

    PubMed

    Bröer, Ralf

    2006-03-01

    This paper centers on the relationship between renaissance medicine and antitrinitarianism forming an important part of the radical reformation in 16th century. Antitrinitarians denied the theological concept of the triune Christian God. Modern antitriniarianism was first formulated by Michael Servetus, a Spanish physician. The doctrine soon won disciples in northern Italy (Padua, Pisa, Rome) and in some countries of eastern central Europe (Poland, Moravia, Transylvania). Physicians who believed in or sympathized with antitrinitarianism revolutionized the theory of blood flow. They developed new concepts leading to Harvey's theory of the circulation of the blood. Parts of Servet's theory looked like Paracelsus's mystical idea of the eternal flesh of the body of Christ (Latin limbus aeternus), but later the medicine and natural philosophy of antitrinitarian physicians tended to be empiristic, rational and sometimes materialistic. They contributed heavily to the diffusion and physiological foundation of antitrinitarian concepts like unitarianism, tolerance and irenism.

  5. Mechanical Blood Trauma in Assisted Circulation: Sublethal RBC Damage Preceding Hemolysis

    PubMed Central

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

    2016-01-01

    After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory. PMID:27034320

  6. 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.

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

    PubMed Central

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

    2015-01-01

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

  8. Identifying late-onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks' gestation.

    PubMed

    Whitehead, Clare L; McNamara, Helen; Walker, Susan P; Alexiadis, Maria; Fuller, Peter J; Vickers, Daniel K; Hannan, Natalie J; Hastie, Roxanne; Tuohey, Laura; Kaitu'u-Lino, Tu'uhevaha J; Tong, Stephen

    2016-04-01

    Late-onset fetal growth restriction (FGR) is often undetected prior to birth, which puts the fetus at increased risk of adverse perinatal outcomes including stillbirth. Measuring RNA circulating in the maternal blood may provide a noninvasive insight into placental function. We examined whether measuring RNA in the maternal blood at 26-30 weeks' gestation can identify pregnancies at risk of late-onset FGR. We focused on RNA highly expressed in placenta, which we termed "placental-specific genes." This was a case-control study nested within a prospective cohort of 600 women recruited at 26-30 weeks' gestation. The circulating placental transcriptome in maternal blood was compared between women with late-onset FGR (<5th centile at >36+6 weeks) and gestation-matched well-grown controls (20-95th centile) using microarray (n = 12). TaqMan low-density arrays, reverse transcription-polymerase chain reaction (PCR), and digital PCR were used to validate the microarray findings (FGR n = 40, controls n = 80). Forty women developed late-onset FGR (birthweight 2574 ± 338 g, 2nd centile) and were matched to 80 well-grown controls (birthweight 3415 ± 339 g, 53rd centile, P < .05). Operative delivery and neonatal admission were higher in the FGR cohort (45% vs 23%, P < .05). Messenger RNA coding 137 placental-specific genes was detected in the maternal blood and 37 were differentially expressed in late-onset FGR. Seven were significantly dysregulated with PCR validation (P < .05). Activating transcription factor-3 messenger RNA transcripts were the most promising single biomarker at 26-30 weeks: they were increased in fetuses destined to be born FGR at term (2.1-fold vs well grown at term, P < .001) and correlated with the severity of FGR. Combining biomarkers improved prediction of severe late-onset FGR (area under the curve, 0.88; 95% CI 0.80-0.97). A multimarker gene expression score had a sensitivity of 79%, a specificity of 88%, and a positive likelihood ratio of 6.2 for

  9. 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.

  10. Flat-head positioning increases cerebral blood flow in anterior circulation acute ischemic stroke. A cluster randomized phase IIb trial.

    PubMed

    Olavarría, Verónica V; Lavados, Pablo M; Muñoz-Venturelli, Paula; González, Francisca; Gaete, Javier; Martins, Sheila; Arima, Hisatomi; Anderson, Craig S; Brunser, Alejandro M

    2017-01-01

    Background Whether lying-flat improves blood flow in patients with acute ischemic stroke is unknown. Our aim was to investigate if lying-flat "changes" cerebral blood flow velocities assessed by transcranial Doppler in acute ischemic stroke patients. Methods In a multicenter cluster clinical trial, we randomly assigned patients within 12 h from onset of a neurological deficit due to cerebral ischemia of the anterior circulation to lying-flat or upright head positioning. The primary outcome was a change of 8 cm/s or more in mean cerebral blood flow velocities on transcranial Doppler to the middle cerebral artery at 1 and 24 h post-randomization, adjusted for imbalance in baseline variables. Secondary outcomes included serious adverse events and physical functioning at 90 days. Results Ninety-four of 304 patients screened were recruited. The primary outcome occurred in 11 (26%) of 43 patients in the lying-flat group and in 6 (12%) of 51 in the upright group at 1 h (adjusted odds ratio, 3.81; 95% CI, 1.07 to 13.54), and in 23 (53%) and 18 (36%) patients in these respective groups at 24 h (adjusted odds ratio, 3.04; 95% CI, 1.08 to 8.53). There were no between-group differences in serious adverse events, including pneumonia, heart failure or mortality, nor in functional outcome at 3 months (adjusted common odds ratio, 1.38; 95% CI 0.64 to 3.00). Conclusion The lying-flat head position was associated with a significant increase in cerebral blood flow velocities at one and 24 h within the ipsilateral hemisphere of anterior circulation acute ischemic stroke, without serious safety concerns. Clinical trial registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT01706094.

  11. [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.

  12. [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.

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

    NASA Astrophysics Data System (ADS)

    Lee, Shinyoung; Kim, Heui-Baik

    2014-05-01

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

  14. Molecular Biosensing Mechanisms in the Spleen for the Removal of Aged and Damaged Red Cells from the Blood Circulation

    PubMed Central

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

    2010-01-01

    Heinz bodies are intraerythrocytic inclusions of hemichrome formed as a result of hemoglobin (Hb) oxidation. They typically develop in aged red cells. Based on the hypothesis that hemichrome formation is an innate characteristic of physiologically normal Hb molecules, we present an overview of our previous findings regarding the molecular instability of Hb and the formation of hemichrome, as well as recent findings on Heinz body formation within normal human erythrocytes. Human adult Hb (HbO2 A) prepared from healthy donors showed a tendency to produce hemichrome, even at close to physiological temperature and pH. Recent studies found that the number of Heinz bodies formed in red cells increased with increasing temperature when freshly drawn venous blood from healthy donors was subjected to mild heating above 37 °C. These findings suggest that Hb molecules control the removal of non-functional erythrocytes from the circulation via hemichrome formation and subsequent Heinz body clustering. In this review, we discuss the molecular biosensing mechanisms in the spleen, where hemichrome formation and subsequent Heinz body clustering within erythrocytes play a key role in the removal of aged and damaged red cells from the blood circulation. PMID:22163593

  15. 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.

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

    PubMed

    Wang, Tai

    2014-09-01

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

  17. 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.

  18. 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.

  19. [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.

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

    PubMed

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

    2016-07-01

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

  1. Study on time-based variation of blood circulation index, pulse wave energy, and RAI of healthy adult men after different eating times.

    PubMed

    Kim, Gyeong-Cheol; Ji, Ki-Young; Kim, Yi-Soon; Kwak, Yi-Sub

    2013-12-01

    The purpose of this study is to examine the effects of different eating times on blood circulation index, pulse wave energy (E), and radial augmentation index (RAI) of healthy adult men. Blood circulation index, E, and RAI were measured using a three-dimensional (3-D) pulse imaging system (3-D MAC) at before, right after, 30 minutes after, 1 hour after, and 2 hours after eating. In the blood circulation index, heart rate (HR), estimated cardiac output (ECO), and estimated cardiac output index (ECI) increased significantly right after eating compared to before eating. By contrast, estimated circulation resistance (ECR) and estimated circulation resistance index (ECRI) decreased significantly right after eating compared to before eating. E had a tendency to increase right after eating compared to before eating and decrease gradually at every experimental point (left and right Chon, Kwan, and Cheok). RAI had a tendency to decrease right after eating compared to before eating and increase gradually at every experimental point. Different eating times can bring about changes on blood circulation index, E, and RAI. These changes show a certain tendency and coincide with the physiological factors that eating causes a rise of HR, an increase of systolic cardiac pump performance, and a reduction of peripheral vascular resistance.

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

    PubMed Central

    Botkin, Nikolai; Alves-Pinto, Ana

    2014-01-01

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

  3. 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.

  4. [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.

  5. Microphthalmia Transcription Factor as a Molecular Marker for Circulating Tumor Cell Detection in Blood of Melanoma Patients

    PubMed Central

    Koyanagi, Kazuo; O’Day, Steven J.; Gonzalez, Rene; Lewis, Karl; Robinson, William A.; Amatruda, Thomas T.; Kuo, Christine; Wang, He-Jing; Milford, Robert; Morton, Donald L.; Hoon, Dave S.B.

    2010-01-01

    Purpose Microphthalmia transcription factor (Mitf), which is important in melanocyte development and melanoma growth, was assessed using real-time quantitative reverse transcription-PCR assay to investigate its expression as a marker for circulating melanoma cells in blood and determine the correlation with disease stage and survival in melanoma patients. Experimental Design In optimization studies for Mitf, we tested 15 melanoma cell lines, 41 peripheral blood lymphocytes from healthy volunteers, and 21metastatic melanoma tissues. Blood specimens were procured from 90 patients with stage I (n = 20), stage II (n = 20), stage III (n = 28), and stage IV (n = 22) melanoma. Blood specimens were also obtained at four bleed intervals from 58 patients enrolled in a prospective multicenter trial of biochemotherapy before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. Results Under the optimized conditions, Mitf was negative in healthy peripheral blood lymphocytes and positive in all melanoma cell lines and 18 (86%) melanoma tissues. In the 90 patients, the rate of Mitf detection was higher with increasing American Joint Committee on Cancer stage (P < 0.0001). In the 58 patients treated with biochemotherapy and surgery, Mitf detection decreased with treatment (P = 0.019). Mitf detection after treatment was associated with a significantly lower relapse-free (P < 0.0001) and overall (P = 0.001) survival and was a significant independent prognostic factor for relapse-free (risk ratio, 5.63; P = 0.0004) and overall (risk ratio, 5.36; P = 0.005) survival. Conclusions Mitf detection in blood can indicate subclinical metastatic disease and predict treatment outcome in melanoma patients. PMID:16489066

  6. 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

  7. 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

  8. EDTA-mediated inhibition of DNases protects circulating cell-free DNA from ex vivo degradation in blood samples.

    PubMed

    Barra, Gustavo Barcelos; Santa Rita, Ticiane Henriques; de Almeida Vasques, Júlia; Chianca, Camilla Figueiredo; Nery, Lídia Freire Abdalla; Santana Soares Costa, Sandra

    2015-10-01

    The extracellular DNA occurring in plasma-EDTA and serum is a biomarker of growing interest, especially in prenatal diagnosis and oncology. The objectives of the present study were to compare the DNase activity in these specimens and to investigate its ex-vivo impact over the circulating cell-free DNA yield (ccfDNA), using the circulating cell-free fetal DNA (ccffDNA) as a tool. EDTA-plasma and serum from women bearing male fetus were submitted to an endogenous DNase activity assay based on qPCR hydrolysis probe degradation, they were treated with DNAse I to investigate the action of an exogenous nuclease and also submitted to different temperature conditions to investigate the temperature-dependent degradation of the ccffDNA. In all instances, all male ccffDNA were quantified by qPCR targeting the Y chromosome-specific sequence DYS-14. Moreover, a serial dilution of EDTA was added to nonanticoagulated plasma and serum before the endogenous DNAse activity assay, to investigate the EDTA-mediated inhibition of the blood's DNase. The endogenous nuclease activity was 14.9-fold higher in serum compared to EDTA-plasma. The DNAse I treatment did not alter the ccffDNA yields in EDTA-plasma, but completely degraded it in serum. The addition of increasing doses of EDTA to nonanticoagulated plasma and serum resulted in a stepwise inhibition of their nucleases activity. Finally, we observed a much more pronounced temperature-mediated decrease on the ccffDNA amount in serum compared to EDTA-plasma. The exogenous and endogenous DNases are more active in serum, the anticoagulant EDTA indirectly inhibits blood DNases, and consequently ccfDNA is protected from the blood's DNase preanalytical impact in EDTA-plasma. Copyright © 2015. Published by Elsevier Inc.

  9. 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.

  10. 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.

  11. Screening for circulating nucleic acids and caspase activity in the peripheral blood as potential diagnostic tools in lung cancer.

    PubMed

    Roth, Carina; Kasimir-Bauer, Sabine; Pantel, Klaus; Schwarzenbach, Heidi

    2011-06-01

    The focus of the current investigational study was to examine whether circulating nucleic acids (i.e., DNA and microRNAs) have the potential to become suitable blood-based markers for diagnosis and progression of lung cancer. The concentrations of cell-free DNA and four circulating microRNAs (miR10b, miR34a, miR141 and miR155) as well as the caspase activity were measured in serum of 35 lung cancer patients (19 non-small-cell lung cancer, 8 small cell lung cancer patients and 8 patients with indefinite cancer type), 7 patients with benign lung tumors and 28 healthy individuals by PicoGreen, TaqMan MicroRNA, and Caspase-Glo®3/7 assay, respectively. The data were correlated with the established risk factors for lung cancer progression. The concentrations of cell-free DNA (p = 0.0001), serum microRNAs (p = 0.0001) and caspase activities (p = 0.0001) significantly discriminated cancer patients from healthy individuals. Serum DNA, caspase activities and RNA levels could not distinguish between patients with benign lung disease and cancer patients. However, the levels of miR10b (p = 0.002), miR141 (p = 0.0001) and miR155 (p = 0.007) were significantly higher in lung cancer patients than those in patients with benign disease. As determined by the Spearman-Rho test, high levels of cell-free DNA significantly correlated with elevated circulating caspase activities (p = 0.0001). In lung cancer patients high serum miR10b values associated with lymph node metastasis (p < 0.03) and elevated levels of TPA (tissue polypeptide antigen, p = 0.01), whereas high serum miR141 values associated with elevated levels of uPA (urokinase plasminogen activator, p = 0.02). The findings of our pilot study suggest that the assays for circulating DNA, microRNAs and caspase activities in blood might become novel minimally invasive diagnostic tools for detection and risk assessment of lung cancer, provided that their clinical utility can be confirmed in larger prospective trials. Copyright

  12. 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.

  13. Dried-blood spots: a cost-effective field method for the detection of Chikungunya virus circulation in remote areas.

    PubMed

    Andriamandimby, Soa Fy; Heraud, Jean-Michel; Randrianasolo, Laurence; Rafisandratantsoa, Jean Théophile; Andriamamonjy, Seta; Richard, Vincent

    2013-01-01

    In 2005, there were outbreaks of febrile polyarthritis due to Chikungunya virus (CHIKV) in the Comoros Islands. CHIKV then spread to other islands in the Indian Ocean: La Réunion, Mauritius, Seychelles and Madagascar. These outbreaks revealed the lack of surveillance and preparedness of Madagascar and other countries. Thus, it was decided in 2007 to establish a syndrome-based surveillance network to monitor dengue-like illness. This study aims to evaluate the use of capillary blood samples blotted on filter papers for molecular diagnosis of CHIKV infection. Venous blood samples can be difficult to obtain and the shipment of serum in appropriate temperature conditions is too costly for most developing countries. Venous blood and dried-blood blotted on filter paper (DBFP) were collected during the last CHIKV outbreak in Madagascar (2010) and as part of our routine surveillance of dengue-like illness. All samples were tested by real-time RT-PCR and results with serum and DBFP samples were compared for each patient. The sensitivity and specificity of tests performed with DBFP, relative to those with venous samples (defined as 100%) were 93.1% (95% CI:[84.7-97.7]) and 94.4% (95% CI:[88.3-97.7]), respectively. The Kappa coefficient 0.87 (95% CI:[0.80-0.94]) was excellent. This study shows that DBFP specimens can be used as a cost-effective alternative sampling method for the surveillance and monitoring of CHIKV circulation and emergence in developing countries, and probably also for other arboviruses. The loss of sensitivity is insignificant and involved a very small number of patients, all with low viral loads. Whether viruses can be isolated from dried blood spots remains to be determined.

  14. Heparin-coated extracorporeal circulation in combination with low dose systemic heparinization reduces early postoperative blood loss in cardiac surgery.

    PubMed

    Mirow, N; Zittermann, A; Koertke, H; Maleszka, A; Knobl, H; Coskun, T; Kleesiek, K; Koerfer, R

    2008-04-01

    According to a recently performed meta-analysis, heparin-bonded circuits do not reduce blood loss in cardiac surgery patients compared to nonheparin-bonded circuits within the first 24 h postoperatively. We investigated the effects of heparin-coated circuits in combination with a reduced systemic heparin dose on early postoperative blood loss (first 12 h), platelet function, and postoperative complications. Patients who underwent their first coronary artery bypass graft surgery were included in a randomized prospective study. Group A (n=149) was perfused with an uncoated extracorporeal circulation (ECC)-set and groups B (n=152) and C (n=149) with heparin-coated ECC-sets. In groups A and B, conventional dose systemic heparin was given, whereas group C received low dose systemic heparin. Blood loss was assessed within the first 12 h postoperatively. Moreover, biochemical parameters of pro-coagulant activity and immunological function were measured. None of the pro-coagulant activity markers and immunological parameters measured differed preoperatively or postoperatively between study groups. However, intraoperative platelet counts and maximal intraoperative concentrations of platelet factor 4, ss-thromboglobulin, and poly-morpho-nuclear (PMN)-elastase were lowest in group C, whereas group C also had the highest concentrations of thrombin-antithrombin complex (P<0.018-0.001). Blood loss within the first 12 h postoperatively was 457 +/- 204 mL in group A, 431 +/- 178 mL in group B, and 382 +/- 188 mL in group C (P<0.01). Complication rates and 30-day mortality did not differ between study groups. The combined use of heparin-coated circuits and low dose systemic heparinization is able to reduce early postoperative blood loss without enhancing the risk of complications.

  15. Physiological and pathological population dynamics of circulating human red blood cells

    PubMed Central

    Higgins, John M.; Mahadevan, L.

    2010-01-01

    The systems controlling the number, size, and hemoglobin concentrations of populations of human red blood cells (RBCs), and their dysregulation in anemia, are poorly understood. After release from the bone marrow, RBCs undergo reduction in both volume and total hemoglobin content by an unknown mechanism [Lew VL, et al. (1995) Blood 86:334–341; Waugh RE, et al. (1992) Blood 79:1351–1358]; after ∼120 d, responding to an unknown trigger, they are removed. We used theory from statistical physics and data from the hospital clinical laboratory [d'Onofrio G, et al. (1995) Blood 85:818–823] to develop a master equation model for RBC maturation and clearance. The model accurately identifies patients with anemia and distinguishes thalassemia-trait anemia from iron-deficiency anemia. Strikingly, it also identifies many pre-anemic patients several weeks before anemia becomes clinically detectable. More generally we illustrate how clinical laboratory data can be used to develop and to test a dynamic model of human pathophysiology with potential clinical utility. PMID:21059904

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

    USDA-ARS?s Scientific Manuscript database

    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...

  17. 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.

  18. 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.

  19. 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).

  20. 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

  1. 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.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26160844

  3. 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.

  4. Sequential Blood Filtration for Extracorporeal Circulation: Initial Results from a Proof-of-Concept Prototype.

    PubMed

    Herbst, Daniel P

    2014-09-01

    Micropore filters are used during extracorporeal circulation to prevent gaseous and solid particles from entering the patient's systemic circulation. Although these devices improve patient safety, limitations in current designs have prompted the development of a new concept in micropore filtration. A prototype of the new design was made using 40-μm filter screens and compared against four commercially available filters for performance in pressure loss and gross air handling. Pre- and postfilter bubble counts for 5- and 10-mL bolus injections in an ex vivo test circuit were recorded using a Doppler ultrasound bubble counter. Statistical analysis of results for bubble volume reduction between test filters was performed with one-way repeated-measures analysis of variance using Bonferroni post hoc tests. Changes in filter performance with changes in microbubble load were also assessed with dependent t tests using the 5- and 10-mL bolus injections as the paired sample for each filter. Significance was set at p < .05. All filters in the test group were comparable in pressure loss performance, showing a range of 26-33 mmHg at a flow rate of 6 L/min. In gross air-handling studies, the prototype showed improved bubble volume reduction, reaching statistical significance with three of the four commercial filters. All test filters showed decreased performance in bubble volume reduction when the microbubble load was increased. Findings from this research support the underpinning theories of a sequential arterial-line filter design and suggest that improvements in microbubble filtration may be possible using this technique.

  5. Sequential Blood Filtration for Extracorporeal Circulation: Initial Results from a Proof-of-Concept Prototype

    PubMed Central

    Herbst, Daniel P.

    2014-01-01

    Abstract: Micropore filters are used during extracorporeal circulation to prevent gaseous and solid particles from entering the patient’s systemic circulation. Although these devices improve patient safety, limitations in current designs have prompted the development of a new concept in micropore filtration. A prototype of the new design was made using 40-μm filter screens and compared against four commercially available filters for performance in pressure loss and gross air handling. Pre- and postfilter bubble counts for 5- and 10-mL bolus injections in an ex vivo test circuit were recorded using a Doppler ultrasound bubble counter. Statistical analysis of results for bubble volume reduction between test filters was performed with one-way repeated-measures analysis of variance using Bonferroni post hoc tests. Changes in filter performance with changes in microbubble load were also assessed with dependent t tests using the 5- and 10-mL bolus injections as the paired sample for each filter. Significance was set at p < .05. All filters in the test group were comparable in pressure loss performance, showing a range of 26–33 mmHg at a flow rate of 6 L/min. In gross air-handling studies, the prototype showed improved bubble volume reduction, reaching statistical significance with three of the four commercial filters. All test filters showed decreased performance in bubble volume reduction when the microbubble load was increased. Findings from this research support the underpinning theories of a sequential arterial-line filter design and suggest that improvements in microbubble filtration may be possible using this technique. PMID:26357790

  6. 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.

  7. The effect of long-term lithium treatment of bipolar disorder on stem cells circulating in peripheral blood.

    PubMed

    Ferensztajn-Rochowiak, Ewa; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy; Ratajczak, Mariusz Z; Michalak, Michal; Rybakowski, Janusz K

    2017-02-01

    To investigate the effect of long-term lithium treatment on very small embryonic-like stem cells (VSELs), haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) circulating in peripheral blood (PB), in bipolar disorder (BD). The study included 15 BD patients (aged 55 ± 6 years) treated with lithium for 8-40 years (mean 16 years), 15 BD patients (aged 53 ± 7 years) with duration of illness >10 years, who had never received lithium, and 15 healthy controls (aged 50 ± 5 years). The VSELs, HSCs, MSCs and EPCs were measured by flow cytometric analysis. In BD subjects not taking lithium the number of CD34(+ )VSELs was significantly higher, and MSCs and EPCs numerically higher, than in control subjects and the number of CD34(+ )VSELs correlated with the duration of illness. In lithium-treated patients these values were similar to controls and the number of CD34(+ )VSELs correlated negatively with the duration of lithium treatment and serum lithium concentration. Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. [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.

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

    PubMed

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

    2013-01-01

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

  14. 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

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

    PubMed

    Ivanov, K P; Mel'nikova, N N

    2012-12-01

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

  16. [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.

  17. Isolation, identification and characterization of secretory proteins of IVMFC embryos and blood circulation of estrus and early pregnant goat.

    PubMed

    Malakar, Dhruba; Majumdar, A C

    2005-08-01

    The aim of the present study was to isolate, identify and characterize the secretory proteins of IVM oocytes and IVMFC embryos to evaluate its immunogenecity. and identify of such proteins if any, in blood circulation of estrus and early pregnant goats. Oocytes were matured in TCM-199 with 1 microg/ml, estradiol-17beta; 0.5 microg/ml, FSH; 100 IU/ml, LH and 10% FCS on granulosa cell monolayer. After 18 hr of maturation, oocytes were further cultured in maturation medium containing 3 mg/ml polyvinyl alcohol (PVA) without serum and BSA for 12 hr and medium was collected. The IVF embryos of 4-8 cell stage were cultured in medium containing PVA without serum and BSA. Embryo culture medium was collected after 24 hr of culture and was pooled. The proteins were analyzed on SDS-PAGE (12.5%). Four secretory proteins of oocytes with approximately molecular weight of 45, 55, 65 and 95 kDa and three secretory proteins of embryos 45, 55 and 65 kDa were obtained on SDS-PAGE in silver staining. The protein profile of midluteal, estrus and early pregnant goat serum was similar and no variation was observed among the proteins on SDS-PAGE. Two secretory proteins of 55 and 65 kDa of both IVM oocytes and IVMFC embryos were observed on Western analysis. None of such proteins was observed in midluteal, estrus and early pregnant goat serum on western blotting. It can be concluded that IVM oocytes and IVMFC embryos secrete proteins in medium and two of them can develop antibody. The proteins secreted from embryos till morula stage was similar to that of oocytes. None of these oocyte/embryo released proteins were observed in blood circulation of estrus and early pregnant goats.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  19. Impact of a Workplace Health Promotion Program on Employees' Blood Pressure in a Public University.

    PubMed

    Eng, J Y; Moy, F M; Bulgiba, A

    2016-01-01

    Workplace health promotion is important in the prevention of non-communicable diseases among employees. Previous workplace health programs have shown benefits such as lowered disease prevalence, reduced medical costs and improved productivity. This study aims to evaluate the impact of a 6-year workplace health promotion program on employees' blood pressure in a public university. In this prospective cohort study, we included 1,365 employees enrolled in the university's workplace health promotion program, a program conducted since 2008 and using data from the 2008-2013 follow-up period. Participants were permanent employees aged 35 years and above, with at least one follow up measurements and no change in antihypertensive medication during the study period. Baseline socio-demographic information was collected using a questionnaire while anthropometry measurements and resting blood pressure were collected during annual health screening. Changes in blood pressure over time were analyzed using a linear mixed model. The systolic blood pressure in the hypertension subgroup decreased 2.36 mmHg per year (p<0.0001). There was also significant improvement in systolic blood pressure among the participants who were at risk of hypertension (-0.75 mmHg, p<0.001). The diastolic blood pressure among the hypertensive and at risk subgroups improved 1.76 mmHg/year (p<0.001) and 0.56 mmHg/year (p<0.001), respectively. However, there was no change in both systolic and diastolic blood pressure among participants in the healthy subgroup over the 6-year period. This study shows that continuing participation in workplace health promotion program has the potential to improve blood pressure levels among employees.

  20. Impact of a Workplace Health Promotion Program on Employees’ Blood Pressure in a Public University

    PubMed Central

    Eng, J. Y.; Moy, F. M.; Bulgiba, A.

    2016-01-01

    Introduction Workplace health promotion is important in the prevention of non-communicable diseases among employees. Previous workplace health programs have shown benefits such as lowered disease prevalence, reduced medical costs and improved productivity. This study aims to evaluate the impact of a 6-year workplace health promotion program on employees’ blood pressure in a public university. Methods In this prospective cohort study, we included 1,365 employees enrolled in the university’s workplace health promotion program, a program conducted since 2008 and using data from the 2008–2013 follow-up period. Participants were permanent employees aged 35 years and above, with at least one follow up measurements and no change in antihypertensive medication during the study period. Baseline socio-demographic information was collected using a questionnaire while anthropometry measurements and resting blood pressure were collected during annual health screening. Changes in blood pressure over time were analyzed using a linear mixed model. Results The systolic blood pressure in the hypertension subgroup decreased 2.36 mmHg per year (p<0.0001). There was also significant improvement in systolic blood pressure among the participants who were at risk of hypertension (-0.75 mmHg, p<0.001). The diastolic blood pressure among the hypertensive and at risk subgroups improved 1.76 mmHg/year (p<0.001) and 0.56 mmHg/year (p<0.001), respectively. However, there was no change in both systolic and diastolic blood pressure among participants in the healthy subgroup over the 6-year period. Conclusion This study shows that continuing participation in workplace health promotion program has the potential to improve blood pressure levels among employees. PMID:26840508

  1. Effect of Chinese herbal medicine for activating blood circulation and detoxifying on expression of inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.

    PubMed

    Xue, Mei; Zhang, Lu; Yang, Lin; Jiang, Yue-rong; Guo, Chun-yu; Yin, Hui-jun; Chen, Ke-ji

    2010-06-01

    To observe the pharmaceutical effect of Chinese drugs for activating blood circulation (Xiongshao Capsule, XSC, ) and for activating blood circulation and detoxification (Xiongshao Capsule and Huanglian Capsule, XSHLC, ) in terms of the indices of thrombosis, inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats. Fifty Wistar rats were randomly divided into the sham operation group, the model group, the Simvastatin group (SG), the activating blood circulation (ABC) group, and the activating blood circulation and detoxifying (ABCD) group, with 10 rats in each group. Simvastatin (1.8 mg/kg), XSC (0.135 g/kg) and XSHLC (0.135 g/kg) were administered to Simvastatin, ABC and ABCD group by gastrogavage, and an equal volume of normal saline was given to the sham operation group and the model group. After 2 weeks of successive medication, the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model. The serum levels of matrix metalloproteinases (MMP-9), tissue inhibitors to metalloproteinase (TIMP-1), granule membrane protein-140 (GMP-140), tissue-type plasminogen activator (t-PA), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were detected with enzyme-linked immunoassay 24 h later. Compared with the model group, the levels of serum GMP-140, hs-CRP, IL-6 and MMP-9 were significantly decreased, and the level of t-PA was significantly increased in the ABC and ABCD group ( P<0.05), while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group (P<0.05). Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis, inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats. The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to

  2. Lower Blood Pressure-Induced Renal Hypoperfusion Promotes Cisplatin-Induced Nephrotoxicity.

    PubMed

    Mizuno, Tomohiro; Hayashi, Takahiro; Shimabukuro, Yuka; Murase, Maho; Hayashi, Hiroki; Ishikawa, Kazuhiro; Takahashi, Kazuo; Yuzawa, Yukio; Yamada, Shigeki; Nagamatsu, Tadashi

    2016-01-01

    Cisplatin-induced nephrotoxicity primarily occurs in the proximal tubules, and tubular injuries reduce glomerular filtration rates. Lower blood pressure causes renal hypoperfusion, which promotes ischemic acute kidney injury (AKI). Our study examined the relationship between lower blood pressure-induced renal hypoperfusion and cisplatin-induced nephrotoxicity. The relationship between cisplatin use and hypoalbuminemia is not clear. This study consisted of Japanese patients who received cisplatin as the first-line chemotherapy at Fujita Health University Hospital from April 2006 to December 2012. Hypoalbuminemia was defined as serum albumin levels ≤3.5 mg/dl. Patients who experienced lower blood pressure during chemotherapy were included in the lower blood pressure group (n = 229), and those who did not were included in the normal blood pressure group (n = 743). Total cisplatin dose in the normal blood pressure and lower blood pressure groups was 58.9 ± 23.8 and 55.0 ± 20.4 mg/m2, respectively. The rate of severe nephrotoxicity was higher and overall survival was shorter in the lower blood pressure group than in the normal blood pressure group. In a multivariable analysis, lower blood pressure significantly correlated with hypoalbuminemia. To prevent ischemic AKI, nutrition and cachexia controlling are important parts of cancer treatment. © 2016 S. Karger AG, Basel.

  3. 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.

  4. Antegrade selective cerebral perfusion combined with deep hypothermic circulatory arrest on cerebral circulation: comparison between pulsatile and nonpulsatile blood flows.

    PubMed

    Soeda, Masao

    2007-04-01

    In aortic arch surgeries, antegrade selective cerebral perfusion (SCP) combined with deep hypothermic circulatory arrest (DHCA) has been recently widely used in institutions as one of the most reliable methods for cerebral protection. However, some studies reported a 3.7-9.3% incidence of postoperative cerebral complications. To perform antegrade SCP more safely, we sought to examine the impact of pulsatile flow perfusion during DHCA on cerebral tissue metabolism, focusing on physiological effects of pulsatile flow perfusion. Sixteen pigs were divided into 2 groups. In each group, antegrade SCP combined with DHCA was conducted. During circulatory arrest, for SCP, a pulsatile flow (group P) and a nonpulsatile flow (group N) were used. We compared results between group P and group N. Jugular venous oxygen saturation (SjO(2)) and cerebral tissue oxygen partial pressure (PtO(2)) were measured at baseline, and continuously throughout the extracorporeal circulation. Hematocrit (Ht), and concentrations of S-100 protein and CK-BB in blood and the cerebrospinal fluid (CSF) were measured at baseline (before the beginning of extracorporeal circulation), following SCP, and after rewarming. Following rewarming, each brain under perfused fixation was removed, and histopathological examinations were conducted using Kluver-Barrera and Tunnel staining methods, electron micrograph. SjO(2) was found to be within normal ranges until after SCP, but decreased with rewarming in both groups. In Group N, changes in SjO(2) were significant, with a decrease to < or =50%. In Group N, concentrations of S-100 protein and CK-BB in CSF after SCP and after rewarming were significantly higher than those in Group P. The time needed for rewarming to 36 degrees C in Group P was shorter than that in Group N. Our results suggest that the pulsatile flow circulation method shows cerebral protection effects with increasing blood flow in small cerebral tissues. In addition, it is effective for improving the

  5. 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

    2017-09-01

    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. Copyright © 2016 John Wiley & Sons, Ltd.

  6. 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.

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

    PubMed Central

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

    2011-01-01

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

  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. 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

  11. 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.

  12. 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.

  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. [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.

  15. 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.

  16. 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

  17. Low-intensity resistance training with blood flow restriction improves vascular endothelial function and peripheral blood circulation in healthy elderly people.

    PubMed

    Shimizu, Ryosuke; Hotta, Kazuki; Yamamoto, Shuhei; Matsumoto, Takuya; Kamiya, Kentaro; Kato, Michitaka; Hamazaki, Nobuaki; Kamekawa, Daisuke; Akiyama, Ayako; Kamada, Yumi; Tanaka, Shinya; Masuda, Takashi

    2016-04-01

    The present study aimed to investigate the effects of low-intensity resistance training with blood flow restriction (BFR resistance training) on vascular endothelial function and peripheral blood circulation. Forty healthy elderly volunteers aged 71 ± 4 years were divided into two training groups. Twenty subjects performed BFR resistance training (BFR group), and the remaining 20 performed ordinary resistance training without BFR. Resistance training was performed at 20 % of each estimated one-repetition maximum for 4 weeks. We measured lactate (Lac), norepinephrine (NE), vascular endothelial growth factor (VEGF) and growth hormone (GH) before and after the initial resistance training. The reactive hyperemia index (RHI), von Willebrand factor (vWF) and transcutaneous oxygen pressure in the foot (Foot-tcPO2) were assessed before and after the 4-week resistance training period. Lac, NE, VEGF and GH increased significantly from 8.2 ± 3.6 mg/dL, 619.5 ± 243.7 pg/mL, 43.3 ± 15.9 pg/mL and 0.9 ± 0.7 ng/mL to 49.2 ± 16.1 mg/dL, 960.2 ± 373.7 pg/mL, 61.6 ± 19.5 pg/mL and 3.1 ± 1.3 ng/mL, respectively, in the BFR group (each P < 0.01). RHI and Foot-tcPO2 increased significantly from 1.8 ± 0.2 and 62.4 ± 5.3 mmHg to 2.1 ± 0.3 and 68.9 ± 5.8 mmHg, respectively, in the BFR group (each P < 0.01). VWF decreased significantly from 175.7 ± 20.3 to 156.3 ± 38.1 % in the BFR group (P < 0.05). BFR resistance training improved vascular endothelial function and peripheral blood circulation in healthy elderly people.

  18. 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.

  19. 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

  20. 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.

  1. A Double in vivo Biotinylation Technique for Objective Assessment of Aging and Clearance of Mouse Erythrocytes in Blood Circulation

    PubMed Central

    Saxena, Rajiv K.; Bhardwaj, Nitin; Sachar, Sumedha; Puri, Niti; Khandelwal, Sanjay

    2012-01-01

    Summary We have recently developed a new technique to objectively identify erythrocyte cohorts of defined age in mouse blood. The technique (termed double in vivo biotinylation, DIB) involves an initial biotinylation of all erythrocytes in circulation, followed after a few days by a second biotinylation, at a lower density, that labels the biotin-negative erythrocytes that have entered since the first biotinylation. The proportions of biotinhigh, biotinlow, and biotinnegative erythrocytes are enumerated by flow cytometry. The DIB technique allows us to track age-related changes on erythrocyte cohorts (Protocol A), and to simultaneously identify very young and older erythrocyte populations in the blood (Protocol B). Using this technique, we have reexamined: i) the relationship between age and buoyant density of erythrocytes, ii) erythrocyte destruction through a random removal mechanism, and iii) the expression of phosphatidylserine on aging erythrocytes. We have also used the DIB technique to study age-related changes in the expression of various markers like CD47 and CD147 and green autofluorescence in aging erythrocyte populations. PMID:23801925

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

    PubMed

    Kubo, Keitaro; Ikebukuro, Toshihiro

    2012-10-01

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

  3. [Comparative study on the regulatory effects on senescence related cell cycle gene expression by TCM principles of tonifying shen, invigorating pi benefiting qi, and activating blood circulation].

    PubMed

    Chen, Fang-min; Zhao, Wei-kang; Xu, Pin-chu

    2003-11-01

    To compare the effects of TCM therapeutic principles of tonifying Shen (TS), benefiting Qi (BQ), invigorating Pi (IP) and activating blood circulation (ABC) herbs in regulating the gene expression in senescence related cell cycle. Drug sera containing TCM herbs of the above-mentioned principles were used to treat the aged human diploid fibroblast cell line 2BS. The effect of TCM on the senescence related cell cycle and its related gene expression (P16INK4, Cyclin D1 and PCNA) were examined by means of cell proliferative doublings, flow cytometry, RT-PCR and Western blot analysis. TCM herbs of TS and BQ could improve the cell cycle, down-regulate the P16 and Cyclin D1 mRNA/protein expression, up-regulate PCNA mRNA/protein expression, while TCM herbs of IP and ABC showed insignificant effect on these indexes. TCM herbs of TS and BQ have effect in improving cell cycle, it may be achieved through promoting the P16 pathway of gene expression.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production.

    PubMed

    Maggi, Laura; Montaini, Gianni; Mazzoni, Alessio; Rossettini, Beatrice; Capone, Manuela; Rossi, Maria Caterina; Santarlasci, Veronica; Liotta, Francesco; Rossi, Oliviero; Gallo, Oreste; De Palma, Raffaele; Maggi, Enrico; Cosmi, Lorenzo; Romagnani, Sergio; Annunziato, Francesco

    2017-03-01

    Protection against helminths consists of adaptive responses by TH2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice but less so in human subjects. We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous TH2 cells. Circulating ILC2s and TH2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro. ILC2s were then stimulated with phorbol 12-myristate 13-acetate plus ionomycin, IL-25 plus IL-33 (IL-25/IL-33), or a mixture of Toll-like receptor ligands to evaluate their ability to produce cytokines, express CD154, and induce IgE production by autologous B cells. Cytokines and transcription factor gene methylation were assessed. ILC2s expressed GATA-3, retinoic acid orphan receptor (RORC) 2, and RORα; were able to produce IL-5, IL-13, and IL-4; and, accordingly, were characterized by demethylation of IL4, IL13, IL5, GATA3, and RORC2, whereas the IFNG, IFNG promoter, and TBX21 regions of interest were methylated. ILC2s expressed TLR1, TLR4, and TLR6, and TLR stimulation induced IL-5 and IL-13 production. Moreover, ILC2s expressed CD154 in response to phorbol 12-myristate 13-acetate plus ionomycin, IL-25/IL-33, or a mixture of TLR ligands. Stimulated ILC2s also induced IgM, IgG, IgA, and IgE production by B cells. Finally, circulating ILC2s from atopic patients were not different in numbers and frequency but expressed higher IL-4 levels than those from nonatopic subjects. This study provides the first evidence that human ILC2s can express CD154 and stimulate the production of IgE by B lymphocytes through IL-25/IL-33 stimulation or TLR triggering. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. 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

  10. 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.

  11. Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry

    PubMed Central

    Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

    2016-01-01

    Background: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. Objective: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Methods: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. Results: The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Conclusions: Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group. PMID:27858671

  12. 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

  13. 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

  14. Circulating mitochondrial stress 70 protein/mortalin and cytosolic Hsp70 in blood: Risk indicators in colorectal cancer.

    PubMed

    Jubran, Ritta; Kocsis, Judit; Garam, Nóra; Maláti, Éva; Gombos, Tímea; Barabás, Loránd; Gráf, László; Prohászka, Zoltán; Fishelson, Zvi

    2017-08-09

    Mitochondrial mortalin and cytosolic Hsp70 are essential chaperones overexpressed in cancer cells. Our goals were to reproduce our earlier findings of elevated circulating levels of mortalin and Hsp70 in colorectal cancer (CRC) patients with a larger patient cohort, to compare death risk assessment of mortalin, Hsp70, CEA and C19-9 and to assess their prognostic value in various CRC stages. Mortalin, Hsp70, CEA and CA19-9 levels were determined in sera of 235 CRC patients enrolled in the study and followed up 5 years after surgery. Association between their concentrations and patients' survival was analyzed by Kaplan-Meier estimator and subjected to Cox Proportional hazards analysis. Serum level of mortalin was independent of that of Hsp70, CEA and CA19-9, whereas Hsp70 level weakly correlated with CEA and CA19-9 levels. Improved short-term survival was found in early or advanced disease stages associated with lower mortalin and Hsp70 levels. Cox regression analysis showed a high mortality hazard (HR = 3.7, p < 0.001) in patients with both high mortalin and Hsp70 circulating levels. Multivariate analysis showed that high mortalin and Hsp70 significantly enhances risk score over a baseline model of age, number of affected lymph nodes, CEA, CA19-9, disease stage and perioperative therapy. Analysis of mortalin and Hsp70 in CRC patients' sera adds a high prognostic value to TNM stage and to CEA and CA19-9 and identifies patients with lower or higher survival probability in all CRC stages. Determination of mortalin and Hsp70 in blood could be a useful additive prognostic tool in guiding clinical management of patients. © 2017 UICC.

  15. Enteric-formulated lactoferrin was more effectively transported into blood circulation from gastrointestinal tract in adult rats.

    PubMed

    Takeuchi, Takashi; Jyonotsuka, Takahiro; Kamemori, Nao; Kawano, Genji; Shimizu, Hirohiko; Ando, Kunio; Harada, Etsumori

    2006-11-01

    We have previously demonstrated that intestinally infused bovine lactoferrin (bLF) is transported into the blood circulation via the lymphatic pathway, not via the portal circulation. Therefore, in the present study, we further investigated whether intragastrically infused enteric-formulated bLF (EF-bLF) was more efficiently absorbed than bLF from the intestine in adult rats. The rats were randomly divided into three groups: 30 and 300 mg kg(-1) non-enteric-formulated bLF (non-EF-bLF) groups and a 30 mg kg(-1) EF-bLF group. Thoracic lymph was collected from a thoracic lymph duct under general anaesthesia. Bovine lactoferrin was infused into the stomach or duodenal lumen via a needle for a period of over 1 min in a volume of 1 ml kg(-1). The bLF transported into the lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent assay (ELISA). Following the intragastric administration of bLF, the three groups showed almost the same lymph flow, but the bLF concentration in the lymph fluid in the EF-bLF group increased significantly and peaked 3 h after administration. With intraduodenal administration, the bLF concentration in the lymph fluid of the higher non-EF-bLF group was significantly higher than those of the other groups. The amount of absorbed bLF in the EF-bLF group was, however, about 10 times higher than that in the lower non-EF-bLF group, when it was administered intragastrically. These data show that enteric-formulated bLF is less susceptible to gastric pepsin and is more efficiently absorbed from the intestine than is non-enteric-formulated bLF.

  16. Identification of loss of heterozygosity on circulating free DNA in peripheral blood of prostate cancer patients: potential and technical improvements.

    PubMed

    Müller, Imke; Beeger, Cord; Alix-Panabières, Catherine; Rebillard, Xavier; Pantel, Klaus; Schwarzenbach, Heidi

    2008-04-01

    Accurate identification of loss of heterozygosity (LOH) on circulating free DNA is often restricted by technical limitations such as poor quality and quantity of tumor-specific DNA and contamination by normal DNA. However, plasma DNA may harbor tumor-specific genetic alterations and could therefore be an interesting target for noninvasive examinations of tumor DNA. By PCR-based fluorescence microsatellite analysis using 12 polymorphic markers, we investigated LOH on cell-free DNA in blood plasma from 59 patients with localized prostate cancer (PCa) and 12 with metastatic disease (MPCa). In addition, plasma DNA from 21 PCa patients was fractionated into high- and low-molecular-weight DNA by 2 different column systems. To avoid appearance of artificial allelic loss and stabilize the amplification, TMAC (tetramethylammonium chloride) was added to each PCR. Overall incidences of LOH at all markers analyzed were 10% in PCa and 12% in MPCa samples. Highest frequencies were found at markers D11S898 (28%) in PCa and D6S1631 (27%) in MPCa. Statistical evaluation showed significant associations between LOH and increasing Gleason scores for the marker combinations D6S1631*D8S286*D9S171 (P = 0.03) and D8S286*D9S171 (P = 0.05). Fractionation of plasma DNA resulted in a higher overall LOH frequency in the low-molecular-weight DNA fraction (23%) compared with the high-molecular-weight DNA (7%). LOH analysis of circulating DNA can provide tumor-specific genetic information on PCa patients. Fractionation of plasma DNA and addition of TMAC improved LOH detection and general assay performance.

  17. 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.

  18. 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

  19. 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

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

    PubMed

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

    2009-01-01

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

  1. Reduced expression of CD47 during murine red blood cell (RBC) senescence and its role in RBC clearance from the circulation.

    PubMed

    Khandelwal, Sanjay; van Rooijen, Nico; Saxena, Rajiv K

    2007-09-01

    Almost 2 percent of murine blood red blood cells (RBCs) are destroyed each day and are replaced by fresh RBCs generated through the process of erythropoiesis. RBCs to be destroyed are phagocytosed by macrophages in the reticuloendothelial system, especially in the spleen. CD47 molecules on RBCs may regulate the susceptibility of RBC to destruction by phagocytosis because its recognition by inhibitory receptor (signal regulatory protein alpha) on macrophages sends a negative signal, which if sufficiently strong, may abort the phagocytic response altogether. The aim of this study was to investigate whether age-dependent changes in CD47 expression on circulating RBCs have a role in destruction of senescent RBCs by macrophages. A two-step in vivo biotinylation method for labeling mouse RBCs in vivo was used to track the CD47 expression levels as well as the turnover of circulating RBCs of defined age groups. Our results indicate that CD47 expression levels decrease on circulating RBCs throughout their life span in circulation. The oldest RBCs in circulation have 30 percent lower mean expression of CD47 than the youngest RBCs. Depletion of macrophages by administration of clodronate-loaded liposomes resulted in a significant decrease in the mean expression of CD47 on RBCs of all age groups and a significant accumulation of senescent RBCs in blood and spleen. A decrease in mean expression of CD47 and accumulation of senescent RBCs in macrophage-depleted mice were significantly higher for spleen RBCs compared to blood RBCs. Our results provide supportive evidence for a role of decreasing CD47 expression on aging circulating RBCs in their destruction by macrophages.

  2. Resveratrol-Loaded Albumin Nanoparticles with Prolonged Blood Circulation and Improved Biocompatibility for Highly Effective Targeted Pancreatic Tumor Therapy

    NASA Astrophysics Data System (ADS)

    Geng, Tao; Zhao, Xia; Ma, Meng; Zhu, Gang; Yin, Ling

    2017-06-01

    Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances across cell membranes. Herein, we have designed and prepared resveratrol (RV)-loaded HSA nanoparticles conjugating RGD (arginine-glycine-aspartate) via a polyethylene glycol (PEG) "bridge" (HRP-RGD NPs) for highly effective targeted pancreatic tumor therapy. HRP-RGD NPs possess an average size of 120 ± 2.6 nm with a narrow distribution, a homodisperse spherical shape, a RV encapsulation efficiency of 62.5 ± 4.21%, and a maximum RV release ratio of 58.4.2 ± 2.8% at pH 5.0 and 37 °C. In vitro biocompatibility of RV is improved after coating with HSA and PEG. Confocal fluorescence images show that HRP-RGD NPs have the highest cellular uptake ratio of 47.3 ± 4.6% compared to HRP NPs and HRP-RGD NPs with free RGD blocking, attributing to an RGD-mediated effect. A cell counting kit-8 (CCK-8) assay indicates that HRP-RGD NPs without RV (HP-RGD NPs) have nearly no cytotoxicity, but HRP-RGD NPs are significantly more cytotoxic to PANC-1 cells compared to free RV and HRP NPs in a concentration dependent manner, showing apoptotic morphology. Furthermore, with a formulated PEG and HSA coating, HRP-RGD NPs prolong the blood circulation of RV, increasing approximately 5.43-fold (t1/2). After intravenous injection into tumor-bearing mice, the content of HRP-RGD NPs in tumor tissue was proven to be approximately 3.01- and 8.1-fold higher than that of HRP NPs and free RV, respectively. Based on these results, HRP-RGD NPs were used in an in vivo anti-cancer study and demonstrated the best tumor growth suppression effect of all tested drugs with no relapse, high in vivo biocompatibility, and no significant systemic toxicity over 35 days treatment. These results demonstrate that HRP-RGD NPs with prolonged blood circulation and improved biocompatibility have high anti-cancer effects with promising future applications in cancer therapy.

  3. Resveratrol-Loaded Albumin Nanoparticles with Prolonged Blood Circulation and Improved Biocompatibility for Highly Effective Targeted Pancreatic Tumor Therapy.

    PubMed

    Geng, Tao; Zhao, Xia; Ma, Meng; Zhu, Gang; Yin, Ling

    2017-12-01

    Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances across cell membranes. Herein, we have designed and prepared resveratrol (RV)-loaded HSA nanoparticles conjugating RGD (arginine-glycine-aspartate) via a polyethylene glycol (PEG) "bridge" (HRP-RGD NPs) for highly effective targeted pancreatic tumor therapy. HRP-RGD NPs possess an average size of 120 ± 2.6 nm with a narrow distribution, a homodisperse spherical shape, a RV encapsulation efficiency of 62.5 ± 4.21%, and a maximum RV release ratio of 58.4.2 ± 2.8% at pH 5.0 and 37 °C. In vitro biocompatibility of RV is improved after coating with HSA and PEG. Confocal fluorescence images show that HRP-RGD NPs have the highest cellular uptake ratio of 47.3 ± 4.6% compared to HRP NPs and HRP-RGD NPs with free RGD blocking, attributing to an RGD-mediated effect. A cell counting kit-8 (CCK-8) assay indicates that HRP-RGD NPs without RV (HP-RGD NPs) have nearly no cytotoxicity, but HRP-RGD NPs are significantly more cytotoxic to PANC-1 cells compared to free RV and HRP NPs in a concentration dependent manner, showing apoptotic morphology. Furthermore, with a formulated PEG and HSA coating, HRP-RGD NPs prolong the blood circulation of RV, increasing approximately 5.43-fold (t1/2). After intravenous injection into tumor-bearing mice, the content of HRP-RGD NPs in tumor tissue was proven to be approximately 3.01- and 8.1-fold higher than that of HRP NPs and free RV, respectively. Based on these results, HRP-RGD NPs were used in an in vivo anti-cancer study and demonstrated the best tumor growth suppression effect of all tested drugs with no relapse, high in vivo biocompatibility, and no significant systemic toxicity over 35 days treatment. These results demonstrate that HRP-RGD NPs with prolonged blood circulation and improved biocompatibility have high anti-cancer effects with promising future applications in cancer

  4. Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression.

    PubMed

    Roth, Carina; Pantel, Klaus; Müller, Volkmar; Rack, Brigitte; Kasimir-Bauer, Sabine; Janni, Wolfgang; Schwarzenbach, Heidi

    2011-01-06

    As cell-free circulating DNA exists predominantly as mono- and oligonucleosomes, the focus of the current study was to examine the interplay of circulating nucleosomes, DNA, proteases and caspases in blood of patients with benign and malignant breast diseases. The concentrations of cell-free DNA and nucleosomes as well as the protease and caspase activities were measured in serum of patients with benign breast disease (n = 20), primary breast cancer (M0, n = 31), metastatic breast cancer (M1, n = 32), and healthy individuals (n = 28) by PicoGreen, Cell Death Detection ELISA, Protease Fluorescent Detection Kit and Caspase-Glo®3/7 Assay, respectively. Patients with benign and malignant tumors had significantly higher levels of circulating nucleic acids in their blood than healthy individuals (p = 0.001, p = 0.0001), whereas these levels could not discriminate between benign and malignant lesions. Our analyses of all serum samples revealed significant correlations of circulating nucleosome with DNA concentrations (p = 0.001), nucleosome concentrations with caspase activities (p = 0.008), and caspase with protease activities (p = 0.0001). High serum levels of protease and caspase activities associated with advanced tumor stages (p = 0.009). Patients with lymph node-positive breast cancer had significantly higher nucleosome levels in their blood than node-negative patients (p = 0.004). The presence of distant metastases associated with a significant increase in serum nucleosome (p = 0.01) and DNA levels (p = 0.04), and protease activities (p = 0.008). Our findings demonstrate that high circulating nucleic acid concentrations in blood are no indicators of a malignant breast tumor. However, the observed changes in apoptosis-related deregulation of proteolytic activities along with the elevated serum levels of nucleosomes and DNA in blood are linked to breast cancer progression.

  5. 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.

  6. 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.

  7. [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.

  8. A motivational interview promotes retention of blood donors with high internal motivation.

    PubMed

    France, Christopher R; France, Janis L; Carlson, Bruce W; Himawan, Lina K; Kessler, Debra A; Rebosa, Mark; Shaz, Beth H; Madden, Katrala; Carey, Patricia M; Slepian, P Maxwell; Ankawi, Brett; Livitz, Irina E; Fox, Kristen R

    2017-10-01

    Based on the hypothesis that self-determined motivation is associated with an increased likelihood of future behavior, the present study examined the ability of a motivational interview to promote internal motivation for giving blood and future donation attempts. A sample of 484 recent whole-blood and double red blood cell donors (62.4% female; age = 30.2 ± 11.8 years) were randomly assigned to either a telephone-delivered motivational interview or a control call approximately 6 weeks after donating. Several weeks before the call and again 1 week after the call, participants completed the Blood Donor Identity Survey, a multidimensional measure of donor motivation, to derive indices of amotivation, external motivation, and internal motivation to give blood. Repeat donation attempts were tracked using blood center records. Relative to controls, participants in the motivational interview group showed a shift toward more self-determined motivation, as indicated by significant decreases in amotivation (p = 0.01) and significant increases in external (p = 0.009) and internal (p = 0.002) motivation. Furthermore, those with initially high levels of autonomous motivation were more likely to make a donation attempt in the subsequent year if they completed the motivational interview (71.1%) versus the control call (55.1%). Motivational interviewing is a potentially useful strategy to enhance retention of existing blood donors, particularly among those who express a greater sense of internal motivation for giving. © 2017 AABB.

  9. Evaluation of blood flow distribution asymmetry and vascular geometry in patients with Fontan circulation using 4-D flow MRI.

    PubMed

    Jarvis, Kelly; Schnell, Susanne; Barker, Alex J; Garcia, Julio; Lorenz, Ramona; Rose, Michael; Chowdhary, Varun; Carr, James; Robinson, Joshua D; Rigsby, Cynthia K; Markl, Michael

    2016-10-01

    Asymmetrical caval to pulmonary blood flow is suspected to cause complications in patients with Fontan circulation. The aim of this study was to test the feasibility of 4-D flow MRI for characterizing the relationship between 3-D blood flow distribution and vascular geometry. We hypothesized that both flow distribution and geometry can be calculated with low interobserver variability and will detect a direct relationship between flow distribution and Fontan geometry. Four-dimensional flow MRI was acquired in 10 Fontan patients (age: 16 ± 4 years [mean ± standard deviation], range: 9-21 years). The Fontan connection was isolated by 3-D segmentation to evaluate flow distribution from the inferior vena cava (IVC) and superior vena cava (SVC) to the left and right pulmonary arteries (LPA, RPA) and to characterize geometry (cross-sectional area, caval offset, vessel angle). Flow distribution results indicated SVC flow tended toward the RPA while IVC flow was more evenly distributed (SVC to RPA: 78% ± 28 [9-100], IVC to LPA: 54% ± 28 [4-98]). There was a significant relationship between pulmonary artery cross-sectional area and flow distribution (IVC to RPA: R(2)=0.50, P=0.02; SVC to LPA: R(2)=0.81, P=0.0004). Good agreement was found between observers and for flow distribution when compared to net flow values. Four-dimensional flow MRI was able to detect relationships between flow distribution and vessel geometry. Future studies are warranted to investigate the potential of patient specific hemodynamic analysis to improve diagnostic capability.

  10. Circulating Tumor Cells and Tumor Stem Cells Detection in the Peripheral Blood Mononuclear Cells of Breast Cancer.

    PubMed

    Wang, Feng; Li, Yuan-Chun; Liu, Li-Ping; Zhang, Hao-Min; Tong, Song

    2016-09-01

    Our aim was to retrospectively analyze the relationships between circulating tumor cells (CTCs) and the development of breast cancer, for elucidating the role of CTCs in breast cancer. A total of 107 female patients with primary breast cancer and 48 matched healthy female volunteers were recruited. After blood collection, isolation of peripheral blood mononuclear cells (PBMC) was performed followed by the detection of cytokeratin 19 positive (CK19(+) ) and CD44(+) /CD24(-/low) cells, as well as estrogen receptor (ER), progesterone, and CerbB2. Data were analyzed with the SPSS 20.0 software. None of the 48 volunteers were detected with CK19(+) cells in their PBMC, while in 77 patients, 72% of 107 female patients with primary breast cancer, the CK19(+) cells were detected. CK19(+) could also be detected among patients in each grouping by different clinical staging and lymph node metastasis, with statistical differences (all P < 0.05). Further, among the 83 CK19(+) specimens, 32 were also detected with CD44(+) /CD24(-/low) cells. Comparisons of CK19(+) and CD44(+) /CD24(-/low) cells in patients with different clinical features (ER positive vs. ER negative, C-erbB2 positive vs. C-erbB2 negative) and molecular subtypes (triple-negative breast cancer, ER positive, and C-erbB2 positive) showed no obvious difference (all P > 0.05). Both CTCs and tumor stem cells (TSCs) could be detected in the PBMC of breast cancer patients; besides, positive expression rate of CTCs might be obviously associated with the clinical stage and metastasis. Positive relationship of TSCs and the clinical stage of breast cancer was also proved in this study. © 2016 Wiley Periodicals, Inc.

  11. 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.

  12. Presence and active synthesis of the 67 kDa elastin-receptor in human circulating white blood cells.

    PubMed

    Larbi, Anis; Levesque, Georges; Robert, Ladislas; Gagné, Daniéle; Douziech, Nadine; Fülöp, Tamas

    2005-07-08

    Early after the identification of the elastin-receptor (El-R) on mesenchymal cells, it was demonstrated that phagocytic cells and lymphocytes could also respond to elastin peptides. Nevertheless, the level of El-R expression has never been demonstrated on immune cells and no data exist whether these cells actively synthesize this El-R. Thus, our aim in the present work was to study the expression and number of El-R on white blood cells (WBC) using a specific 67 kDa El-R antibody and to demonstrate the presence of mRNA corresponding to the gene coding for El-R. Our results show that messenger RNA corresponding to the presumptive gene coding for the 67 kDa El-R subunit could be detected in all three WBC-types investigated. On all of these WBC, the presence of El-R could be demonstrated, however their number and their function varied following the cell type. The presence of El-R is very important for the interaction of circulating cell with the matrix as these cells intervene during atherosclerosis and in host defence.

  13. Evaluation of Two Different Analytical Methods for Circulating Tumor Cell Detection in Peripheral Blood of Patients with Primary Breast Cancer

    PubMed Central

    Jaeger, B. A. S.; Jueckstock, J.; Andergassen, U.; Salmen, J.; Schochter, F.; Fink, V.; Alunni-Fabbroni, M.; Rezai, M.; Beck, Th.; Beckmann, M. W.; Friese, K.; Friedl, T. W. P.; Janni, W.; Rack, B.

    2014-01-01

    Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT. PMID:24800234

  14. 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.

  15. 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.

  16. 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.

  17. Computed tomography-guided screening of surfactant effect on blood circulation time of emulsions: application to the design of an emulsion formulation for paclitaxel.

    PubMed

    Lee, Eun-Hye; Hong, Soon-Seok; Kim, So Hee; Lee, Mi-Kyung; Lim, Joon Seok; Lim, Soo-Jeong

    2014-08-01

    In an effort to apply the imaging techniques currently used in disease diagnosis for monitoring the pharmacokinetics and biodisposition of particulate drug carriers, we sought to use computed tomography (CT) scanning methodology to investigate the impact of surfactant on the blood residence time of emulsions. We prepared the iodinated oil Lipiodol emulsions with different compositions of surfactants and investigated the impact of surfactant on the blood residence time of emulsions by CT scanning. The blood circulation time of emulsions was prolonged by including Tween 80 or DSPE-PEG (polyethylene glycol 2000) in emulsions. Tween 80 was less effective than DSPE-PEG in terms of prolongation effect, but the blood circulating time of emulsions was prolonged in a Tween 80 content-dependent manner. As a proof-of-concept demonstration of the usefulness of CT-guided screening in the process of formulating drugs that need to be loaded in emulsions, paclitaxel was loaded in emulsions prepared with 87 or 65% Tween 80-containing surfactant mixtures. A pharmacokinetics study showed that paclitaxel loaded in 87% Tween 80 emulsions circulated longer in the bloodstream compared to those in 65% Tween 80 emulsions, as predicted by CT imaging. CT-visible, Lipiodol emulsions enabled the simple evaluation of surfactant composition effects on the biodisposition of emulsions.

  18. 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.

  19. Comparative metabolomics analysis on invigorating blood circulation for herb pair Gui-Hong by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and pattern recognition approach.

    PubMed

    Li, Shujiao; Lin, Hang; Tang, Yuping; Li, Weixia; Shen, Juan; Kai, Jun; Yue, Shijun; Shang, Guanxiong; Zhu, Zhenhua; Shang, Erxin; Zhang, Changbin; Zhang, Li; Yan, Hui; Liu, Pei; Duan, Jin-ao

    2015-03-25

    The compatibility of Angelicae Sinensis Radix (Danggui, DG) and Flos Carthami (Honghua, HH), a famous herb pair Gui-Hong (GH), can produce synergistic and promoting blood effects. Although some physiological and pathological function parameters of the acute blood stasis have been investigated, little information about the changes of small metabolites in biofluids has been reported. In present study, global metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) combined with pattern recognition method was performed to discover the underlying blood-activating regulation mechanisms of DG, HH and GH on the acute blood stasis rats induced by subcutaneous injection of adrenaline hydrochloride and ice water bath. The total 14 metabolites (10 in urine and 4 in plasma), up regulated or down regulated (P<0.05 or 0.01), were identified and contributed to the acute blood stasis progress. These promising identified biomarkers underpin the metabolic pathway including phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism and arginine and proline metabolism are disturbed in the acute blood stasis rats, which identified by using pathway analysis with MetPA. The altered metabolites and hemorheological indexes could be regulated closer to normal level after DG, HH and GH intervention. In term of activate blood circulation function, GH was the most effective as shown by the relative distance in PLS-DA score plots and relative intensity of metabolomics trategy, reflecting the synergic action between Danggui and Honghua. The results demonstrated that biofluids metabolomics was a powerful tool in clinical diagnosis and treatment of syndrome of blood stasis for providing information on changes in metabolites pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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).