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Sample records for artery urokinase infusion

  1. Transradial approach for transcatheter selective superior mesenteric artery urokinase infusion therapy in patients with acute extensive portal and superior mesenteric vein thrombosis.

    PubMed

    Wang, Mao Qiang; Guo, Li Ping; Lin, Han Ying; Liu, Feng Yong; Duan, Feng; Wang, Zhi Jun

    2010-02-01

    The purpose of this investigation was to assess the feasibility and effectiveness of transradial approach for transcatheter superior mesenteric artery (SMA) urokinase infusion therapy in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were treated by transcatheter selective SMA urokinase infusion therapy by way of the radial artery. The mean age of the patients was 39.5 years. Through the radial sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of urokinase was performed for 5-11 days (7.1 +/- 2.5 days). Adequate anticoagulation was given during treatment, throughout hospitalization, and after discharge. Technical success was achieved in all 16 patients. Substantial clinical improvement was seen in these 16 patients after the procedure. Minor complications at the radial puncture site were observed in 5 patients, but trans-SMA infusion therapy was not interrupted. Follow-up computed tomography scan before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The 16 patients were discharged 9-19 days (12 +/- 6.0 days) after admission. Mean duration of follow-up after hospital discharge was 44 +/- 18.5 months, and no recurrent episodes of PV-SMV thrombosis developed during that time period. Transradial approach for transcatheter selective SMA urokinase infusion therapy in addition to anticoagulation is a safe and effective therapy for the management of patients with acute extensive PV-SMV thrombosis.

  2. Transradial Approach for Transcatheter Selective Superior Mesenteric Artery Urokinase Infusion Therapy in Patients with Acute Extensive Portal and Superior Mesenteric Vein Thrombosis

    SciTech Connect

    Wang Maoqiang Guo Liping; Lin Hanying; Liu Fengyong; Duan Feng; Wang Zhijun

    2010-02-15

    The purpose of this investigation was to assess the feasibility and effectiveness of transradial approach for transcatheter superior mesenteric artery (SMA) urokinase infusion therapy in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were treated by transcatheter selective SMA urokinase infusion therapy by way of the radial artery. The mean age of the patients was 39.5 years. Through the radial sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of urokinase was performed for 5-11 days (7.1 {+-} 2.5 days). Adequate anticoagulation was given during treatment, throughout hospitalization, and after discharge. Technical success was achieved in all 16 patients. Substantial clinical improvement was seen in these 16 patients after the procedure. Minor complications at the radial puncture site were observed in 5 patients, but trans-SMA infusion therapy was not interrupted. Follow-up computed tomography scan before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The 16 patients were discharged 9-19 days (12 {+-} 6.0 days) after admission. Mean duration of follow-up after hospital discharge was 44 {+-} 18.5 months, and no recurrent episodes of PV-SMV thrombosis developed during that time period. Transradial approach for transcatheter selective SMA urokinase infusion therapy in addition to anticoagulation is a safe and effective therapy for the management of patients with acute extensive PV-SMV thrombosis.

  3. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    SciTech Connect

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-03-15

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate.

  4. Tirofiban combined with urokinase selective intra-arterial thrombolysis for the treatment of middle cerebral artery occlusion

    PubMed Central

    FENG, LEI; LIU, JUN; LIU, YUNZHEN; CHEN, JIAN; SU, CHUNHAI; LV, CHUANFENG; WEI, YUZHEN

    2016-01-01

    The aims of the present study were to establish a model of embolic stroke in rabbits and to evaluate the efficacy and safety of intra-arterially administered tirofiban combined with urokinase thrombolysis. The middle cerebral artery occlusion model (MCAO) of embolic stroke was established in New Zealand rabbits via an autologous clot. The model rabbits were allocated at random into four groups: Tirofiban group (T group), urokinase group (UK group), tirofiban and urokinase group (T + UK group) and the control group (C group). The recanalization rate, relative-apparent diffusion coefficient (rADC) and neurological function deficit score (NFDS) values were compared among the four groups. The recanalization rate, rADC and NFDS values were improved in the T + UK group compared with the other groups. In summary, the intra-arterial administration of tirofiban combined with urokinase thrombolysis was a more effective intervention in an MCAO model compared with intra-arterial urokinase alone, and may promote reperfusion and reduce infarct volume. PMID:26998029

  5. Mixing during intravertebral arterial infusions in an in vitro model.

    PubMed

    Lutz, Robert J; Warren, Kathy; Balis, Frank; Patronas, Nicholas; Dedrick, Robert L

    2002-06-01

    Regional delivery of drugs can offer a pharmacokinetic advantage in the treatment of localized tumors. One method of regional delivery is by intra-arterial infusion into the basilar/vertebral artery network that provides local access to infratentorial tumors, which are frequent locations of childhood brain cancers. Proper delivery of drug by infused solutions requires adequate mixing of the infusate at the site of infusion within the artery lumen. Our mixing studies with an in vitro model of the vertebral artery network indicate that streaming of drug solution is likely to occur at low, steady infusion rates of 2 ml/min. Streaming leads to maldistribution of drug to distal perfused brain regions and may result in toxic levels in some regions while concurrently yielding subtherapeutic levels in adjacent regions. According to our model findings, distribution to both brain hemispheres is not likely following infusion into a single vertebral artery even if the infusate is well-mixed at the infusion site. This outcome results from the unique fluid flow properties of two converging channels, which are represented by the left and right vertebral branches converging into the basilar. Fluid in the model remains stratified on the side of the basilar artery served by the infused vertebral artery. Careful thought and planning of the methods of intravertebral drug infusions for treating posterior fossa tumors are required to assure proper distribution of the drug to the desired tissue regions. Improper delivery may be responsible for some noted toxicities or for failure of the treatments. PMID:12164691

  6. Pulmonary Arterial Hypertension: A Focus on Infused Prostacyclins.

    PubMed

    Stewart, Traci

    2016-01-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed. PMID:27598071

  7. Hepatobiliary scintigraphy in patients receiving hepatic artery infusion chemotherapy

    SciTech Connect

    Housholder, D.F.; Hynes, H.E.; Dakhil, S.R.; Marymont, J.H. Jr.

    1984-01-01

    Two patients receiving hepatic artery infusion chemotherapy (HAIC) required cholecystectomy for both acute and chronic cholecystitis with cholelithiasis suggesting chemical cholecystitis. To evaluate the incidence of gall bladder dysfunction in patients receiving HAIC, the authors performed hepatobiliary scintigraphy using Tc-99m DISIDA or PIPIDA on eight patients receiving HAIC through an indwelling hepatic artery catheter and Infusaid (trademark) pump. In 7 of 8 patients, there was non-visualization of the gall bladder throughout the hepatobiliary study. In the eighth patient, the gall bladder visualized at 2 hr. One patient with non-visualization of the gall bladder at 4 hr developed acute symptoms requiring cholecystectomy which showed acute and chronic cholecystitis with cholethiasis. There was prominent sclerosis which was thought to be due to chemical cholecystitis as well as cholelithiasis. In all 10 patients, no evidence of cholecystitis had been observed during the surgical placement of the hepatic artery catheter and Infusaid pump. The hepatobiliary scintigraphic finding of gall bladder dysfunction in all eight patients studied is most likely due to chemical cholecystitis from HAIC. This series suggests that chemical cholecystitis is common during HAIC and can be identified by hepatobiliary scintigraphy. The authors consider elective cholecystectomy during the operative placement of the hepatic artery catheter and Infusaid pump.

  8. Concurrent Middle Cerebral Artery Occlusion and Intra-arterial Drug Infusion via Ipsilateral Common Carotid Artery Catheter in the Rat

    PubMed Central

    Van Winkle, Jessica A.; Chen, Bo; Lei, I-Farn; Pereira, Benedict; Rajput, Padmesh S.; Lyden, Patrick D.

    2012-01-01

    Pre-clinical development of therapy for acute ischemic stroke requires robust animal models; the rodent middle cerebral artery occlusion (MCAo) model using a nylon filament inserted into the internal carotid artery is the most popular. Drug screening requires targeted delivery of test substance in a controlled manner. To address these needs, we developed a novel method for delivering substances directly into the ischemic brain during MCAo in the awake rat. An indwelling catheter is placed in the common carotid artery ipsilateral to the occlusion at the time of the surgical placement of the occluding filament. The internal and common carotid arteries are left patent to allow superfusion anterograde. The surgeries can be completed quickly to allow rapid recovery from anesthesia; tests substances can be infused at any given time for any given duration. To simulate clinical scenarios, the occluding filament can be removed minutes or hours later (reperfusion) followed by therapeutic infusions. By delivering drug intra-arterially to the target tissue, “first pass” loss in the liver is reduced and drug effects are concentrated in the ischemic zone. To validate our method, rats were infused with Evans blue dye either intra-arterially or intravenously during a 4 hour MCAo. After a 30 minute reperfusion period, the dye was extracted from each hemisphere and quantitated with a spectrophotometer. Significantly more dye was measured in the ischemic hemispheres that received the dye intra-arterially. PMID:23261656

  9. Safety of Chemotherapeutic Infusion or Chemoembolization for Hepatocellular Carcinoma Supplied Exclusively by the Cystic Artery

    SciTech Connect

    Kang, Beomsik Kim, Hyo-Cheol Chung, Jin Wook Hur, Saebeom Joo, Seung-Moon Jae, Hwan Jun Park, Jae Hyung

    2013-10-15

    Purpose: This study was designed to evaluate the safety of chemotherapeutic infusion or chemoembolization by way of the cystic artery in patients with hepatocellular carcinoma (HCC) supplied exclusively by the cystic artery. Methods: Between Jan 2002 and Dec 2011, we performed chemotherapeutic infusion or chemoembolization using iodized oil for the treatment of 27 patients with HCC supplied exclusively by the cystic artery. Computed tomography (CT) scans, digital subtraction angiograms, and medical records were retrospectively reviewed by consensus. Results: The cystic artery originated from the main right hepatic artery in 24 (89 %) patients, from the right anterior hepatic artery in 2 (7 %) patients, and from the left hepatic artery in 1 (4 %) patient. Selective catheterization of the cystic artery was achieved in all patients. Superselection of tumor-feeding vessels from the cystic artery was achieved in 7 patients (26 %). Chemotherapeutic infusion was performed in 18 patients (67 %), and chemoembolization was performed in 9 patients (33 %). There were no major complications and only 2 minor complications, including vasovagal syncope and nausea with vomiting. Individual tumor response supplied exclusively by the cystic artery at the follow-up enhanced CT scan were complete response (n = 16), partial response (n = 3), and stable disease (n = 8). Conclusion: HCC supplied exclusively by the cystic artery can be safely treated without severe complications by chemotherapeutic infusion or chemoembolization using iodized oil through the cystic artery.

  10. Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

    SciTech Connect

    Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya; Ujita, Masuo; Irie, Takeo; Fukuda, Yasushi; Fukuda, Kunihiko; Tada, Shimpei

    1999-09-15

    We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

  11. Intra-arterial infusion of leptin does not affect blood pressure in salt-loaded rabbits.

    PubMed

    Mohammad, Mukhallad A; Talafih, Khalid; Mohamad, Mohamad M J; Khabaz, Mohammad Nidal

    2010-08-01

    The aim of this research is to see the effect of intra-arterial infusion of leptin on blood pressure of salt loaded rabbits in vivo. Increased blood pressure was produced in rabbits by giving diets containing 8% sodium chloride for 5 weeks. Leptin in different concentrations was infused intra-arterially into rabbits fed on high salt diets and the response was compared in rabbits fed with low salt diets. High salt diets produced significant increase in blood pressure. In rabbits fed with low salt diet, leptin infused intra-arterially caused an increase in blood pressure while infusion of leptin into rabbits fed with high salt diets does not affect the blood pressure. In conclusion, salt loading to rabbits abolishes the effect ofleptin on cardiovascular system. This may indicate that leptin effect on sympathetic activity is altered by high salt diets in these animals.

  12. Effects of intraoperative diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery

    PubMed Central

    Erdem, Ozan; Memetoğlu, Mehmet Erdem; Tekin, Ali İhsan; Arslan, Ümit; Akkaya, Özgür; Kutlu, Rasim; Gölbaşı, İlhan

    2015-01-01

    Objective This study aimed to show the effects of intra-operative diltiazem infusion on flow in arterial and venous grafts in coronary artery bypass graft surgery. Methods Hundred fourty patients with a total of 361 grafts [205 (57%) arterial and 156 (43%) venous] underwent isolated coronary surgery. All the grafts were measured by intraoperative transit time flow meter intra-operatively. Group A (n=70) consisted of patients who received diltiazem infusion (dose of 2.5 microgram/kg/min), and Group B (n=70) didn't receive diltiazem infusion. Results Mean graft flow values of left internal mammary artery were 53 ml/min in Group A and 40 ml/min in Group B (P<0.001). Pulsatility index (PI) values of left internal mammary artery for Group A and Group B were 2.6 and 3.0 respectively (P<0.001). No statistically significant difference was found between venous graft parameters. Conclusion We recommend an effect of diltiazem infusion in increasing graft flows in coronary artery bypass graft operations. PMID:27163420

  13. Duplex/colour Doppler sonography: measurement of changes in hepatic arterial haemodynamics following intra-arterial angiotensin II infusion.

    PubMed

    Leen, E; Angerson, W J; Warren, H W; Goldberg, J A; Sutherland, G R; Cooke, T G; McArdle, C S

    1993-06-01

    Angiotensin II (AT-II) has been used to target regionally-administered cytotoxic microspheres in patients with intrahepatic tumours. The optimisation of vasoconstrictor targeting requires a knowledge of the blood flow changes induced by agents such as AT-II. We therefore assessed duplex/colour Doppler sonography (DCDS) as a means of evaluating the effects of AT-II infusion on hepatic arterial blood flow (HABF) and arterial resistance in patients with intrahepatic tumours. HABF was measured continuously in nine patients using DCDS before, during and after an infusion of AT-II (15 micrograms in 3 ml of saline over 90 s) via a hepatic artery catheter. In seven patients with less than 30% hepatic replacement by tumour, the baseline level of HABF was 331 +/- 85 ml min-1 (mean +/- s.d.), and this was reduced by 75-80% within 30 s of the start of AT-II infusion. HABF recovered rapidly from the end of the infusion, and increased by up to 20% above the baseline for approximately 2 min. In two patients with greater than 50% hepatic replacement, HABF showed no reduction but rose continuously from the start of AT-II infusion, increasing by a factor of 2-2.5 after 3-4 min. Arterial resistance showed reciprocal changes in all cases. We conclude that DCDS is effective in assessing the temporal changes in hepatic arterial blood flow caused by AT-II. In order to optimise tumour targeting, the injection of microspheres loaded with cytotoxic drugs should be completed before the end of the AT-II infusion. The targeting advantage of AT-II in patients with a high percentage hepatic replacement by tumour should be re-assessed.

  14. [First pass effect by infusing 99mTc-human serum albumin into the hepatic artery].

    PubMed

    Ozawa, T; Kimura, K; Koyanagi, Y; Aoki, T; Kusama, M; Takagi, S; Kakuta, T; Yoshimatsu, A; Ishikawa, M; Yasuda, D

    1988-08-01

    The fundamental principles of intra-arterial infusion chemotherapy are thought to be increased local drug concentration and the "first-pass" effect. The concentration in the rest of the body can only be decreased if there is local elimination of the infused drug before reaching the systemic circulation. This is referred to as the "first-pass" effect. In the evaluation of "first-pass" effect, the uptake of liver after infusing 99mTc-human serum albumin (99mTc-HSA) in the hepatic artery by injecting the subcutaneously implanted silicon reservoir was compared with that obtained after intravenous administration of 99mTc-HSA. In order to remove the factor of portal infusion, each count of liver up take had been continued for only 24 seconds after starting the liver uptake. The results are as follows: for 24 cases excepting 6 cases with catheter obstruction, the mean i.a./i.v. ratio was 7.92 +/- 3.34 (range 3.25 to 17.25). Although the elimination rate of drugs in the liver varies with each drug, the infusion of intraarterial chemotherapy should be about 8 times more concentrative than intravenous administration on the "first-pass" effect.

  15. Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

    PubMed Central

    Jacobs, Joely D.; Hopper-Borge, Elizabeth A.

    2014-01-01

    When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse’s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time. PMID:25407935

  16. A bilateral antidiuresis to renal artery infusion of prostaglandin E1 in dogs treated with phenylbutazone

    PubMed Central

    Hall, W. J.; Hensey, O. J.; O'Neill, P.; Sheehan, J. D.

    1978-01-01

    1. In acute experiments, high levels of endogenous prostaglandins, provoked by operative stress, could obscure or alter the actions of infused prostaglandins on the kidney. For this reason we decided to compare the effects of infusing prostaglandin E1 into the renal artery of the dog before and after the administration of phenylbutazone, a prostaglandin synthetase inhibitor. 2. Infusion of prostaglandin E1 into the left renal artery of the pre-phenylbutazone treated dog undergoing a mannitol diuresis increased renal plasma flow, glomerular filtration rate and the excretion of salt and water. The findings are in general agreement with those reported by others. 3. Following phenylbutazone administration the vascular and saluretic actions of prostaglandin E1 were unchanged but a reduced diuretic effect was observed. The response to a low dose of prostaglandin E1 (0·05 μg/min) was reduced from 1·46 ± 0·15 to 0·96 ± 0·16 ml./min (P < 0·001) and the response to a high dose (0·5 μg/min) from 1·82 ± 0·19 to 0·99 ± 0·31 ml./min (P < 0·002). 4. A significantly less dilute urine was excreted during prostaglandin infusion in the dog after phenylbutazone treatment than before. The reduction in the diuretic response was of the same order as the decrease in the free water clearance response, while the increase in osmolar clearance was unchanged. 5. In water-loaded dogs treated with phenylbutazone, infusion of prostaglandin E1 into the left renal artery had a biphasic effect on urine output from the left kidney. An initial diuretic response to a low dose of prostaglandin E1 disappeared with the infusion of higher doses, and antidiuresis developed in the immediate post-infusion period. 6. As prostaglandin was infused into the left kidney progressive antidiuresis was seen in the non-infused right kidney. 7. It is concluded that endogenous prostaglandins do not obscure or alter the vascular and saluretic actions of intrarenal prostaglandin E1. The findings question

  17. Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat

    SciTech Connect

    Saris, S.C.; Wright, D.C.; Oldfield, E.H.; Blasberg, R.G.

    1988-02-01

    Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer--/sup 14/C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions.

  18. Impact of Multislice CT Angiography on Planning of Radiological Catheter Placement for Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Sone, Miyuki Kato, Kenichi; Hirose, Atsuo; Nakasato, Tatsuhiko; Tomabechi, Makiko; Ehara, Shigeru; Hanari, Takao

    2008-01-15

    The objective of this study was to assess prospectively the role of multislice CT angiography (MSCTA) on planning of radiological catheter placement for hepatic arterial infusion chemotherapy (HAIC). Forty-six patients with malignant liver tumors planned for HAIC were included. In each patient, both MSCTA and intra-arterial digital subtraction angiography (DSA) were performed, except one patient who did not undergo DSA. Comparison of MSCTA and DSA images was performed for the remaining 45 patients. Detectability of anatomical variants of the hepatic artery, course of the celiac trunk, visualization scores of arterial branches and interobserver agreement, presence of arterial stenosis, and technical outcome were evaluated. Anatomical variations of the hepatic artery were detected in 19 of 45 patients (42%) on both modalities. The course of the celiac trunk was different in 12 patients. The visualization scores of celiac arterial branches on MSCTA/DSA were 3.0 {+-} 0/2.9 {+-} 0.2 in the celiac trunk, 3.0 {+-} 0/2.9 {+-} 0.3 in the common hepatic artery, 2.9 {+-} 0.2/2.9 {+-} 0.3 in the proper hepatic artery, 2.9 {+-} 0.3/2.9 {+-} 0.4 in the right hepatic artery, 2.8 {+-} 0.4/2.9 {+-} 0.4 in the left hepatic artery, 2.9 {+-} 0.2/2.9 {+-} 0.3 in the gastroduodenal artery, 2.1 {+-} 0.8/2.2 {+-} 0.9 in the right gastric artery, and 2.7 {+-} 0.8/2.6 {+-} 0.8 in the left gastric artery. No statistically significant differences exist between the two modalities. Interobserver agreement for MSCTA was equivalent to that for DSA. Two patients showed stenosis of the celiac trunk on both modalities. Based on these imaging findings, technical success was accomplished in all patients. In conclusion, MSCTA is accurate in assessing arterial anatomy and abnormalities. MSCTA can provide adequate information for planning of radiological catheter placement for HAIC.

  19. Improved Arterial Blood Oxygenation Following Intravenous Infusion of Cold Supersaturated Dissolved Oxygen Solution

    PubMed Central

    Grady, Daniel J; Gentile, Michael A; Riggs, John H; Cheifetz, Ira M

    2014-01-01

    BACKGROUND One of the primary goals of critical care medicine is to support adequate gas exchange without iatrogenic sequelae. An emerging method of delivering supplemental oxygen is intravenously rather than via the traditional inhalation route. The objective of this study was to evaluate the gas-exchange effects of infusing cold intravenous (IV) fluids containing very high partial pressures of dissolved oxygen (>760 mm Hg) in a porcine model. METHODS Juvenile swines were anesthetized and mechanically ventilated. Each animal received an infusion of cold (13 °C) Ringer’s lactate solution (30 mL/kg/hour), which had been supersaturated with dissolved oxygen gas (39.7 mg/L dissolved oxygen, 992 mm Hg, 30.5 mL/L). Arterial blood gases and physiologic measurements were repeated at 15-minute intervals during a 60-minute IV infusion of the supersaturated dissolved oxygen solution. Each animal served as its own control. RESULTS Five swines (12.9 ± 0.9 kg) were studied. Following the 60-minute infusion, there were significant increases in PaO2 and SaO2 (P < 0.05) and a significant decrease in PaCO2 (P < 0.05), with a corresponding normalization in arterial blood pH. Additionally, there was a significant decrease in core body temperature (P < 0.05) when compared to the baseline preinfusion state. CONCLUSIONS A cold, supersaturated dissolved oxygen solution may be intravenously administered to improve arterial blood oxygenation and ventilation parameters and induce a mild therapeutic hypothermia in a porcine model. PMID:25249764

  20. Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III colorectal cancer: a retrospective study

    PubMed Central

    Wang, Yao; Sun, Xin Rong; Feng, Wen Ming; Bao, Ying; Zheng, Yin Yuan

    2016-01-01

    Background Radical resection is the main treatment for colorectal cancer (CRC), but metastasis or recurrence is common in which liver metastasis accounted for 83% of the cases. Therefore, the prognosis of patients with advanced CRC may be improved if liver metastasis is prevented. This study aims to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of stage III CRC patients after curative resection. Methods Between 2002 and 2008, 287 stage III CRC patients who had undergone radical resection were included in this study. According to postoperative adjuvant chemotherapy modality, these patients were divided into two groups. Patients in the combined therapy group received two cycles of HAIC plus four cycles of systemic chemotherapy, while patients in the monotherapy group received six cycles of systemic chemotherapy alone. The HAIC regimen consisted of hepatic arterial infusion of oxaliplatin (OXA, 85 mg/m2) on day 1 and 5-fluorouracil (5-FU, 2,400 mg/m2) on days 2 and 3 followed by a vein infusion of folinic acid (FA, 200 mg/m2) as a 2-hour infusion on days 2 and 3. The systemic chemotherapy regimen consisted of a 2-hour infusion of OXA (85 mg/m2) on day 1 followed by FA (200 mg/m2) as a 2-hour infusion on days 2 and 3, and by 5-FU (2,400 mg/m2) as a 48-hour infusion. This was repeated every 4 weeks. All cases were followed up for 5 years or until death. The 5-year overall survival, disease-free survival, liver metastases-free survival, and the overall liver metastases rates were retrospectively compared. Results Significant differences were found in the 5-year overall survival (combined therapy, 70.71%; monotherapy, 57.14%; P=0.014), disease-free survival (combined therapy, 69.29%; monotherapy, 55.78%; P=0.021), and liver metastases-free survival rates (combined therapy, 70%; monotherapy, 56.46%; P=0.019). Conclusion Prophylactic adjuvant HAIC can prevent metachronous liver metastases and improve the prognosis of patients

  1. Clinical Variables Correlated with Numbers of Intra-arterial Nimodipine Infusion in Patients with Medically Refractory Cerebral Vasospasm

    PubMed Central

    Kim, Sang-Young; Kim, Ki-Hong; Cho, Jae-Hoon

    2015-01-01

    Objective The objective of this study was to find out the clinical variables correlated with repeated intra-arterial (IA) nimodipine infusions in patients with medically refractory cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH). Materials and Methods During the 36 months between January 2011 and December 2013, 275 patients were treated at our institute for SAH due to a ruptured intracranial aneurysm. Of the 275 patients, 26 patients (9.5%) met the inclusion criteria. For each patient, a retrospective review of their medical records was conducted. Results Eleven patients underwent a single IA nimodipine infusion and 15 patients underwent more than two IA nimodipine infusions. Multiple IA nimodipine infusion patients had poor improvement (2 of 15 patients, 13.3%) in Glasgow coma scale (GCS) scores after the first IA nimodipine infusion compared to patients of single IA nimodipine infusion (6 of 11 patients, 54.6%) (p = 0.038). The mean middle cerebral artery (MCA) Lindegaard ratio of multiple IA nimodipine infusion patients was 4.3 ± 1.1 after the first IA nimodipine infusion (p = 0.039). In multiple IA nimodipine infusion patients, CV occurred more often bilaterally (p = 0.035) and distally (p = 0.001). More vessel segments were affected in multiple IA nimodipine infusion patients (3.1 ± 1.0) (p < 0.001). Conclusion The following factors correlated with multiple IA nimodipine infusions: 1) no improvement in GCS after the IA nimodipine infusion; 2) no decrease of MCA velocity on transcranial doppler over 50 cm/s or Lindegaard ratio over 4.3 after the IA nimodipine infusion; 3) distal, bilateral, or diffuse involvement of CV. PMID:26523251

  2. Infusion of recombinant human tissue plasminogen activator through the superior mesenteric artery in the treatment of acute mesenteric venous thrombosis.

    PubMed

    da Motta Leal Filho, Joaquim Mauricio; Santos, Aline Cristine Barbosa; Carnevale, Francisco Cesar; de Oliveira Sousa, Wilson; Grillo, Luiz Sérgio Pereira; Cerri, Giovanni Guido

    2011-08-01

    Acute mesenteric venous thrombosis is an uncommon condition that is usually treated with systemic anticoagulation. Catheter-directed thrombolysis through the superior mesenteric artery may be a viable adjunct to treat this morbid condition. In the present article, we have described a case of superior mesenteric venous thrombosis treated with catheter-directed infusion of tissue plasminogen activator through the superior mesenteric artery.

  3. Changes in the endocochlear potential and cochlear blood flow induced by ATP infusion and arterial occlusion.

    PubMed

    Hu, B; Jiang, S; Gu, R

    1995-06-01

    To assess the relationship between cochlear blood flow (CBF) and auditory function, a procedure of intravital microscopy for observations of the lateral wall vessels of the cochlea coupled with the simultaneous measurement of the endocochlear potential (EP) was established in guinea pigs with gradual ischemia of the cochlea. It was found that occlusions of both common carotid arteries and one of the vertebral arteries produced a minor reduction in CBF with no significant alteration in the EP. When intravenous infusion of ATP induced sharp and severe decreases in CBF, the EP varied only slightly from the baseline in some animals while there were no alteration in others. Furthermore, ATP infusions combined with arterial occlusions caused even more severe declines in CBF and a moderate decrease in the EP. The results indicate that not only does the CBF satisfy the basic needs of the processes of cochlear function, but also has a regulatory mechanism to ensure the normal function of the cochlea in the ischemia condition. It was also found that the changes in the stria vascularis vessels induced by decreases in blood pressure (BP) and heart rates were more severe than those of the spiral ligament vessels. This phenomenon indicated that the stria vascularis vessels were more sensitive to decreases of BP and heart rates. PMID:7555252

  4. Overexpression of endothelial nitric oxide synthase improves endothelium-dependent vasodilation in arteries infused with helper-dependent adenovirus.

    PubMed

    Jiang, Bo; Du, Liang; Flynn, Rowan; Dronadula, Nagadhara; Zhang, Jingwan; Kim, Francis; Dichek, David

    2012-11-01

    Adenoviral vectors (Ad) are useful tools for in vivo gene transfer into endothelial cells. However, endothelium-dependent vasodilation is impaired after Ad infusion, and this impairment is not prevented by use of advanced-generation "helper-dependent" (HD) Ad that lack all viral genes. We hypothesized that endothelium-dependent vasodilation could be improved in Ad-infused arteries by overexpression of endothelial nitric oxide synthase (eNOS). We tested this hypothesis in hyperlipidemic, atherosclerosis-prone rabbits because HDAd will likely be used for treating and preventing atherosclerosis. Moreover, the consequences of eNOS overexpression might differ in normal and atherosclerosis-prone arteries and could include atherogenic effects, as reported in transgenic mice. We cloned rabbit eNOS and constructed an HDAd that expresses it. HDAdeNOS increased NO production by cultured endothelial cells and increased arterial eNOS mRNA in vivo by ∼10-fold. Compared to arteries infused with a control HDAd, HDAdeNOS-infused arteries of hyperlipidemic rabbits had significantly improved endothelium-dependent vasodilation, and similar responses to phenylephrine and nitroprusside. Moreover, infusion of HDAdeNOS had local atheroprotective effects including large, significant decreases in intimal lipid accumulation and arterial tumor necrosis factor (TNF)-α expression (p≤0.04 for both). HDAdeNOS infusion yields a durable (≥2 weeks) increase in arterial eNOS expression, improves vasomotor function, and reduces artery wall inflammation and lipid accumulation. Addition of an eNOS expression cassette improves the performance of HDAd, has no harmful effects, and may reduce atherosclerotic lesion growth.

  5. Effects of arterial and venous volume infusion on coronary perfusion pressures during canine CPR.

    PubMed

    Gentile, N T; Martin, G B; Appleton, T J; Moeggenberg, J; Paradis, N A; Nowak, R M

    1991-08-01

    Intraarterial (IA) volume infusion has been reported to be more effective than intravenous (IV) infusion in treating cardiac arrest due to exsanguination. A rapid IA infusion was felt to raise intraaortic pressure and improve coronary perfusion pressure (CPP). The purpose of this study was to determine if IA or IV volume infusion could augment the effect of epinephrine on CPP during CPR in the canine model. Nineteen mongrel dogs with a mean weight of 26.3 +/- 4.2 kg were anesthetized and mechanically ventilated. Thoracic aortic (Ao), right atrial (RA) and pulmonary artery catheters were placed for hemodynamic monitoring. Additional Ao and central venous catheters were placed for volume infusion. Ventricular fibrillation was induced and Thumper CPR was begun after 5 min (t = 5). At t = 10, all dogs received 45 micrograms/kg IV epinephrine. Six animals received epinephrine alone (EPI). Five dogs received EPI plus a 500 cc bolus of normal saline over 3 min intravenously (EPI/IV). Another group (n = 8) received EPI plus the same fluid bolus through the aortic catheter (EPI/IA). Resuscitation was attempted at t = 18 using a standard protocol. There was a significant increase in CPP over baseline in all groups. The changes in CPP from baseline induced by EPI, EPI/IV and EPI/IA were 20.6 +/- 3.7, 22.8 +/- 4.2 and 22.2 +/- 2.4 mmHg, respectively. Volume loading did not augment the effect of therapeutic EPI dosing. By increasing both preload and afterload, volume administration may in fact be detrimental during CPR. PMID:1658894

  6. Changes in distribution of hepatic blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer

    SciTech Connect

    Sasaki, Y.; Imaoka, S.; Hasegawa, Y.; Nakano, S.; Ishikawa, O.; Ohigashi, H.; Taniguchi, K.; Koyama, H.; Iwanaga, T.; Terasawa, T.

    1985-01-15

    Changes in the distribution of the hepatic blood flow induced by intra-arterial infusion of angiotensin II (AT-II) were studied in human hepatic cancers using extremely short-lived radioisotope (RI) (krypton 81 m (/sup 81m/Kr); half-life, 13 seconds). After the start of continuous infusion of AT-II, the radioactivity of the tumor showed about a two-fold increase, whereas that of the nontumor region decreased to about one half as much as the level before the infusion. Consequently, the mean ratio of the arterial blood flow in the tumor region to that in the nontumor region (T/N ratio) increased to 3.30 (P less than 0.001). The T/N ratio showed a peak before the peripheral blood pressure reached the maximum, and thereafter tended to decrease. Intra-arterial infusion of AT-II raised the T/N ratio more obviously than did intravenous infusion of the drug, with less rise in the peripheral blood pressure. It is believed that intra-arterial infusion chemotherapy with local use of AT-II enables better accessibility of chemotherapeutic drugs to tumors.

  7. Continuous Regional Arterial Infusion Therapy for Acute Necrotizing Pancreatitis Due to Mycoplasma pneumoniae Infection in a Child

    SciTech Connect

    Nakagawa, Motoo Ogino, Hiroyuki; Shimohira, Masashi; Hara, Masaki; Shibamoto, Yuta

    2009-05-15

    A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.

  8. Influence of colloid infusion on coagulation during off-pump coronary artery bypass grafting

    PubMed Central

    Muralidhar, K; Garg, Rajnish; Mohanty, SK; Banakal, Sanjay

    2010-01-01

    This study was conducted to determine the influence of colloid infusion on coagulation in patients undergoing off-pump coronary artery bypass grafting (OP-CABG). Thirty patients undergoing elective OP-CABG received medium molecular weight hydroxyethyl starch group I (MMW-HES 200/0.5), low molecular weight hydroxyethyl starch group II (LMW-HES 130/0.4) or gelatin group III (GEL) in a prospective randomized trial. Blood samples were assessed for hemoglobin (Hb), activated coagulation time (ACT), prothrombin time (PT), activated partial thromboplastin time (aPPT), platelet count, fibrinogen and von Willebrand factor (vWF) at specified intervals. Total volume of the colloid infused and postoperative chest-time drainage was also measured. There was a significant decrease in Hb, platelet count, fibrinogen levels in all these groups, which did not warrant blood transfusion. After the colloid infusion, vWF decreased significantly to 67% from baseline in group I as compared to 85 and 79% in group II and group III, respectively. vWF levels remained lower than the baseline value in the first 24 hours in group I, whereas this factor level increased above the baseline values in groups II and III, 6 hours postoperatively. Postoperative chest tube drainage in 24 hours was significantly higher in group I (856 ± 131 ml) as compared to group II (550 ± 124 ml) and group III (582 ± 159 ml). LMW-HES 130/0.4 was superior to MMW-HES 200/0.5 and gelatin in patients undergoing OP-CABG, in terms of better preservation of coagulation associated with enhanced volume effect. PMID:20661354

  9. Hepatic Arterial Infusion Chemotherapy Combined with Venous Embolization in a Patient with Hepatic Metastases with an Arteriovenous Shunt

    SciTech Connect

    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Sakaguchi, Hiroshi; Yamamoto, Kiyosei; Inoue, Masayoshi; Sueyoshi, Satoru; Shinnkai, Takayuki; Hasegawa, Masatoshi; Kichikawa, Kimihiko

    2009-07-15

    We describe herein a patient who had hepatic metastases with an arteriovenous shunt and was treated by hepatic arterial infusion chemotherapy. The arteriovenous shunt was diagnosed by {sup 99m}Tc-macroaggregated albumin scintigraphy and hepatic venous embolization was performed to reduce shunt flow.

  10. Efficacy of Intra-Arterial Infusion Chemotherapy for Head and Neck Cancers Using Coaxial Catheter Technique: Initial Experience

    SciTech Connect

    Tsurumaru, Daisuke Kuroiwa, Toshiro; Yabuuchi, Hidetake; Hirata, Hideki; Higaki, Yuichiro; Tomita, Kichinobu

    2007-04-15

    The aim of this study was to evaluate the efficacy of intra-arterial infusion chemotherapy for head and neck cancers using a coaxial catheter technique: the superficial temporal artery (STA)-coaxial catheter method. Thirty-one patients (21 males and 10 females; 37-83 years of age) with squamous cell carcinoma of the head and neck (maxilla, 2; epipharynx, 4; mesopharynx, 8; oral floor, 4; tongue, 10; lower gingiva, 1; buccal mucosa, 2) were treated by intra-arterial infusion chemotherapy. Four patients were excluded from the tumor-response evaluation because of a previous operation or impossibility of treatment due to catheter trouble. Forty-eight sessions of catheterization were performed. A guiding catheter was inserted into the STA and a microcatheter was advanced into the tumor-feeding artery via the guiding catheter under angiographic guidance. When the location of the tumor or its feeding artery was uncertain on angiography, computed tomographic angiography was performed. The anticancer agent carboplatin (CBDCA) was continuously injected for 24 h through the microcatheter from a portable infusion pump attached to the patient's waist. The total administration dose was 300-1300 mg per body. External radiotherapy was administered during intra-arterial chemotherapy at a total dose of 21-70.5 Gy.The initial response was complete response in 15 patients, partial response in 7 patients, and no change in 5 patients; the overall response rate was 81.5% (22/27). Complication-related catheter maintenance was observed in 15 of 48 sessions of catheterization. Injury and dislocation of the microcatheter occurred 10 times in 7 patients. Catheter infection was observed three times in each of two patients, and catheter occlusion and vasculitis occurred in two patients. Intra-arterial infusion chemotherapy via the STA-coaxial catheter method could have potential as a favorable treatment for head and neck tumors.

  11. Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

    SciTech Connect

    Cao Wei; Li Jing; Wu Zhiqun; Zhou Changxi; Liu Xi; Wan Yi; Duan Yunyou

    2013-06-15

    Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 Degree-Sign C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 Degree-Sign C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

  12. Intra-carotid cold magnesium sulfate infusion induces selective cerebral hypothermia and neuroprotection in rats with transient middle cerebral artery occlusion.

    PubMed

    Song, Wei; Wu, Yong-Ming; Ji, Zhong; Ji, Ya-Bin; Wang, Sheng-Nan; Pan, Su-Yue

    2013-04-01

    Local hypothermia induced by intra-arterial infusion of cold saline reduces brain injury in ischemic stroke. Administration of magnesium sulfate through the internal carotid artery is also known to reduce ischemic brain damage. The neuroprotective effects of combination therapy with local endovascular hypothermia and intra-carotid magnesium sulfate infusion has not been evaluated. The aim of the study was to determine whether infusion of intra-carotid cold magnesium offers neuroprotective efficacy superior to cold saline infusion alone. Sixty-eight Sprague-Dawley rats were subjected to 3 h of middle cerebral artery occlusion and were randomly divided into six groups: sham-operated group; stroke control group; local cold magnesium infusion group; local cold saline infusion group; local normothermic magnesium infusion group; and local normothermic saline infusion group. Before reperfusion, ischemic rats received local infusion or no treatment. Infarct volume, neurological deficit, and brain water content were evaluated at 48 h after reperfusion. Selective brain hypothermia (33-34 °C) was successfully induced by intra-carotid cold infusion. Local cold saline infusion and local cold magnesium infusion reduced the infarct volumes by 48 % (p < 0.001) and 65 % (p < 0.001), respectively, compared with stroke controls. Brain water content was decreased significantly in animals treated with local cold magnesium infusion. Furthermore, the rats given a local cold magnesium infusion had the best neurological outcome. Local normothermic infusion failed to improve ischemic brain damage. These data suggest that local hypothermia induced by intra-carotid administration of cold magnesium is more effective in reducing acute ischemic damage than infusion of cold saline alone.

  13. Effects of various arterial infusion solutions on red blood cells in the newborn

    PubMed Central

    Jackson, J.; Derleth, D.

    2000-01-01

    AIM—To examine in vitro the effects of brief contact with various infusion solutions on red blood cells from newborn infants, as occurs in the "waste" syringe during routine blood sampling from umbilical artery catheters. The mixture of blood and solution in the "waste" syringe is usually reinfused into the baby. Reinfused red blood cells may be damaged by the infusion solution. It is hypothesised that an isotonic amino acid solution would cause no red blood cell agglutination and no more haemolysis than many commonly used solutions.
METHODS—Blood was obtained from the placentas of 15 normal term babies. Haemolysis was estimated by measuring plasma (free) haemoglobin after mock blood sampling. Agglutination was measured semiquantitatively by direct observation.
RESULTS—A 0.25% normal saline solution caused 5.4% haemolysis, significantly more than all the other fluids tested. There was less haemolysis with 0.25% normal saline when there was complete mixing of blood and solution within the "waste" syringe. Normal saline and isotonic sodium acetate solutions caused < 0.1% haemolysis, significantly less than all the other fluids tested. The isotonic amino acid solution caused 0.8% haemolysis, which is similar to that caused by the remaining solutions tested. Agglutination was seen with isotonic dextrose and with the two isotonic amino acid solutions containing cysteine.
CONCLUSIONS—Isotonic amino acid solution (without added cysteine) caused no agglutination and the same or less haemolysis than many commonly used solutions and may offer advantages in nutrition and fluid balance.

 PMID:10952708

  14. Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety

    PubMed Central

    Nakamoto, Y; Mizukoshi, E; Tsuji, H; Sakai, Y; Kitahara, M; Arai, K; Yamashita, T; Yokoyama, K; Mukaida, N; Matsushima, K; Matsui, O; Kaneko, S

    2007-01-01

    The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of 111Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity. PMID:17223971

  15. Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients

    PubMed Central

    Gao, Song; Zhang, Peng-Jun; Guo, Jian-Hai; Chen, Hui; Xu, Hai-Feng; Liu, Peng; Yang, Ren-Jie; Zhu, Xu

    2015-01-01

    AIM: To compare the efficacy and safety of chemoembolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy (HAIC), including oxaliplatin (OXA), 5-fluorouracil (5-FU) and folinic acid (CF), in inoperable hepatocellular carcinoma (HCC) without distant metastasis. METHODS: Eighty-four inoperable HCC patients were enrolled. Thirty-nine patients underwent chemoembolization alone, and the other 45 patients underwent chemoembolization + HAIC (OXA/5-FU/CF) treatment non-randomly. The progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse reactions were compared between the two groups. RESULTS: A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS (mPFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease, with or without vessel invasion, the chemoembolization + HAIC group showed better mPFS when compared to chemoembolization alone, but no significant difference was found in patients with BCLC stage C disease. The parameter of pain (grade III-IV) in the chemoembolization + HAIC group was increased statistically. CONCLUSION: Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis. PMID:26420971

  16. [Maxillary Cancer with Metastasis to the Rouviere Nodes -- Complete Response to Chemoradiotherapy Using a Selective Intra-Arterial Infusion Technique].

    PubMed

    Yamashiro, Keita; Heianna, Joichi; Azama, Kimei; Iraha, Yuko; Yamashiro, Tsuneo; Kinoshita, Ryo; Toita, Takafumi; Toyama, Masatomo; Agena, Shinya; Maeda, Hiroyuki; Suzuki, Mikio; Murayama, Sadayuki

    2016-02-01

    We report a case of advanced maxillary cancer with multiple lymph node metastases, including metastasis to the Rouviere nodes, which were successfully treated with chemoradiotherapy using a selective intra-arterial infusion technique.A 71-yearold man presented to our hospital with complaints of a staggering gait and epistaxis.He was diagnosed with maxillary cancer (squamous cell carcinoma)classified as T4a disease.Because multiple lymph node metastases were detected, including metastasis to the Rouviere nodes, radical surgical treatment was considered inadequate.Thus, the patient was treated with concurrent chemoradiotherapy with selective intra-arterial infusion of nedaplatin and docetaxel.After chemoradiotherapy, the maxillary cancer and lymph metastasis nearly resolved and the patient achieved a complete response.No additional surgery was needed, and the patient was discharged.We suggest that chemoradiotherapy using a selective intra-arterial infusion technique is a highly effective treatment option for patients with maxillary cancer and metastasis to the Rouviere nodes.

  17. Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with tumor thrombosis of the portal vein tumor thrombosis

    PubMed Central

    Lai, Yung-Chih; Shih, Cheng-Yen; Jeng, Chin-Ming; Yang, Sien-Sing; Hu, Jui-Ting; Sung, Yung-Chuan; Liu, Han-Ting; Hou, Shaw-Min; Wu, Chi-Hwa; Chen, Tzen-Kwan

    2003-01-01

    AIM: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with poor prognosis. The aim of this prospective study was to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with this disease. METHODS: Eighteen HCC patients with PVTT were treated with HAIC via a subcutaneously implanted injection port. A course of chemotherapy consisted of daily cisplatin (10 mg for one hour) followed by 5-fluorouracil (250 mg for five hours) for five continuous days within a given week. The patients were scheduled to receive four consecutive courses of HAIC. Responders were defined in whom either a complete or partial response was achieved, while non-responders were defined based on stable or progressive disease status. The prognostic factors associated with survival after treatment were analyzed. RESULTS: Six patients exhibited partial response to this form of HAIC (response rate = 33%). The 3, 6, 9, 12 and 18-month cumulative survival rates for the 18 patients were 83%, 72%, 50%, 28%, and 7%, respectively. Median survival times for the six responders and 12 non-responders were 15.0 (range, 11-18) and 7.5 (range, 1-13) months, respectively. It was demonstrated by both univariate and multivariate analyses that the therapeutic response and hepatic reserve function were significant prognostic factors. CONCLUSION: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful alternative for the treatment of patients with advanced HCC complicated with PVTT. There may also be survival-related benefits associated with HAIC. PMID:14669309

  18. 5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved

    PubMed Central

    2012-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. The mesenteric vasculature was chosen as an ideal candidate for the site of 5-HT receptor mediated vascular relaxation given the high percentage of cardiac output the site receives. Real-time RT-PCR demonstrated that mRNA transcripts for the 5-HT2B, 5-HT1B, and 5-HT7 receptors are present in sham and DOCA-salt superior mesenteric arteries. Immunohistochemistry and Western blot validated the presence of the 5-HT2B, 5- HT1B and 5-HT7 receptor protein in sham and DOCA-salt superior mesenteric artery. Isometric contractile force was measured in endothelium-intact superior mesenteric artery and mesenteric resistance arteries in which the contractile 5- HT2A receptor was antagonized. Maximum concentrations of BW-723C86 (5- HT2B agonist), CP 93129 (5-HT1B agonist) or LP-44 (5-HT7 agonist) did not relax the superior mesenteric artery from DOCA-salt rats vs. vehicle. Additionally, 5-HT (10–9 M to 10–5 M) did not cause relaxation in either contracted mesenteric resistance arteries or superior mesenteric arteries from normotensive Sprague- Dawley rats. Thus, although 5-HT receptors known to mediate vascular relaxation are present in the superior mesenteric artery, they are not functional, and are therefore not likely involved in a 5-HT-induced fall in total peripheral resistance and MAP. PMID:22559843

  19. Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases

    SciTech Connect

    Mitsudo, Kenji; Koizumi, Toshiyuki; Iida, Masaki; Iwai, Toshinori; Oguri, Senri; Yamamoto, Noriyuki; Itoh, Yoshiyuki; Kioi, Mitomu; Hirota, Makoto; Tohnai, Iwai

    2012-08-01

    Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer. Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m{sup 2}; CDDP, total 100-150 mg/m{sup 2}) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks. Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively. Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3

  20. Molecular-specific urokinase antibodies

    NASA Technical Reports Server (NTRS)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  1. Effects of arterial infusions of adrenalin and acetylcholine on luteal secretion of progesterone and oxytocin in goats.

    PubMed

    Cooke, R G; Payne, J H

    1998-07-15

    The effects of close intra-arterial infusion of acetylcholine and adrenalin on ovarian secretion of progesterone and oxytocin were examined on Day 10 of the estrous cycle in goats (estrus = Day 0). Acetylcholine (15 micrograms/min) was without effect, but adrenalin (10 micrograms/min) significantly (P < 0.001) raised both progesterone and oxytocin concentrations in ovarian vein plasma. These results show that luteal hormone secretion is enhanced in the goat by beta-adrenergic stimulation and suggest that, as in the sheep and cow, there may be neuroendocrine involvement in the regulation of caprine luteal function. PMID:10734492

  2. Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

    PubMed Central

    Witkowski, Maria Carolina; de Moraes, Maria Antonieta P.; Firpo, Cora Maria F.

    2013-01-01

    OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031]. PMID:24473958

  3. Organ Preservation With Daily Concurrent Chemoradiotherapy Using Superselective Intra-Arterial Infusion via a Superficial Temporal Artery for T3 and T4 Head and Neck Cancer

    SciTech Connect

    Mitsudo, Kenji; Shigetomi, Toshio; Fujimoto, Yasushi; Nishiguchi, Hiroaki; Yamamoto, Noriyuki; Furue, Hiroki; Ueda, Minoru; Itoh, Yoshiyuki; Fuwa, Nobukazu; Tohnai, Iwai

    2011-04-01

    Purpose: To evaluate the therapeutic results and rate of organ preservation in patients with advanced head and neck cancer treated with superselective intra-arterial chemotherapy via a superficial temporal artery and daily concurrent radiotherapy. Methods and Materials: Between April 2002 and March 2006, 30 patients with T3 or T4a squamous cell carcinoma of the head and neck underwent intra-arterial chemoradiotherapy. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m{sup 2}; cisplatin, total 150 mg/m{sup 2}) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. Results: The median follow-up for all patients was 46.2 months (range, 10-90 months). The median follow-up for living patients was 49.7 months (range, 36-90 months). After intra-arterial chemoradiotherapy was administered, primary site complete response was achieved in 30 (100%) of 30 cases. Seven patients (23.3%) died. Using the Kaplan-Meier method, 1-year, 3-year, and 5-year survival rates were 96.7%, 83.1%, and 70.2%, respectively, while 1-year, 3-year, and 5-year local control rates were 83.3%, 79.7%, and 73.0%, respectively. Grade 3 or 4 mucositis occurred in 20 cases (66.7%). Grade 3 toxicities included dysphagia in 20 cases (66.7%), dermatitis in 6 cases (20%), nausea/vomiting in 2 cases (6.7%), and neutropenia and thrombocytopenia in 1 case (3.3%). No osteoradionecrosis of mandible and maxillary bones developed during follow-up. Conclusions: Intra-arterial chemoradiotherapy using a superficial temporal artery provided good overall survival and local control rates. This combination chemoradiotherapy approach can preserve organs and minimize functional disturbance, thus contributing to patients' quality of life.

  4. Reduced liver uptake of arterially infused melphalan during retrograde rat liver perfusion with unaffected liver tumor uptake.

    PubMed

    Rothbarth, Joost; Sparidans, Rolf W; Beijnen, Jos H; Schultze-Kool, Leo J; Putter, Hein; van de Velde, Cornelis J H; Mulder, Gerard J

    2002-11-01

    Isolated hepatic perfusion (IHP) with melphalan is used for patients with nonresectable metastases confined to the liver. To improve the efficacy of IHP and to reduce the toxicity to the liver, reversion (retrograde perfusion) of the bloodstream through the liver in a rat model was studied. For liver tumor induction male WAG/Rij rats were inoculated with CC531 cells, a colorectal tumor cell line. After 11 to 12 days the tumor-bearing rat livers were perfused by single-pass perfusion through either the portal (orthograde) or caval vein (retrograde) for different time periods. During perfusion melphalan (160 Schultze) was infused in the hepatic artery. Melphalan concentrations were measured by high-performance liquid chromatography. A rapid extraction of melphalan by the liver occurred in the first 5 min, reaching steady state after 10 to 20 min for both perfusion directions. The melphalan concentration of the outflow perfusate was significantly higher in the retrograde perfusion compared with the orthograde perfusion. The melphalan content of the tumor tissue was unaffected by perfusion direction at any time point. To the contrary, the melphalan uptake in liver tissue was strongly influenced: the melphalan content after 40-min retrograde perfusion was 12% of that after orthograde perfusion. The average tumor/liver concentration ratio was 6 for orthograde perfusion and 30 for retrograde perfusion. In conclusion, retrograde IHP with continuous melphalan infusion in the hepatic artery provides a high tumor uptake of melphalan with potentially reduced liver toxicity compared with orthograde IHP. PMID:12388659

  5. [99mTc-MIBI myocardial tomography with intravenous infusion of adenosine triphosphate in the diagnosis of coronary artery disease].

    PubMed

    Kumano, S

    1996-02-01

    To evaluate its feasibility, safety and diagnostic accuracy, 99mTc-MIBI myocardial tomography with adenosine triphosphate (ATP) infusion (0.16 mg/kg/min for 5 min) was performed 100 consecutive patients using the stress/rest one day protocol. None of the patients required treatment with aminophylline during the study. The sensitivity and specificity for detecting patients with coronary artery disease were 97% and 71%, respectively. Those for detecting individual coronary lesion (> or = 75% stenosis) were 92% and 89%, respectively. The high hepatic uptake of 99mTc-MIBI causes artifactual perfusion defects in the inferior myocardial wall, particularly on ATP stress images. In order to reduce this artifactual phenomenon, the interval time between injection and stress imaging must be increased. PMID:8721103

  6. Early increase in arterial lactate concentration under epinephrine infusion is associated with a better prognosis during shock.

    PubMed

    Wutrich, Yann; Barraud, Damien; Conrad, Marie; Cravoisy-Popovic, Aurélie; Nace, Lionel; Bollaert, Pierre-Edouard; Levy, Bruno; Gibot, Sébastien

    2010-07-01

    To determine whether an epinephrine-induced early increase in arterial lactate concentration can prognosticate the outcome during shock state, we conducted a retrospective study in a 16-bed medical intensive care unit of a teaching hospital in France. One hundred consecutive patients admitted because of a shock state irrespective of etiology and treated with epinephrine were included. Patients were not enrolled if they received epinephrine administration before intensive care unit admission. Sequential arterial lactate measurements were performed at the time of epinephrine infusion (H0) and 4 h later (H4) in which Deltalactate was defined as (100 x [arterial lactate(H4)-arterial lactate(H0)]/arterial lactate(H0)) and expressed as a percentage. Etiology of shock was septic (82%), cardiogenic (10%), or hemorrhagic (8%). Twenty-eight-day mortality rate was 72%. At admission, arterial lactate concentration was elevated (4.96 +/- 3.8 mmol/L) and was further increased upon epinephrine administration, reaching a peak at H4 (8.22 +/- 3.66). When patients were stratified according to their outcome, nonsurvivors displayed the same pattern as survivors, although with a significant upward shift in values (ANOVA, P = 0.0003). The Sequential Organ Failure Assessment score and Deltalactate were the only variables associated with the 28-day risk of death, with an odds ratio of 1.32 (95% confidence interval [CI], 1.06-1.65; P = 0.01) and 0.99 (95% CI, 0.99-0.99; P = 0.03), respectively, in multivariate analysis. At a value of 100%, Deltalactate predicted death, with a 71% sensitivity (95% CI, 51%-87%) and a 67% specificity (95% CI, 43%-85%). Kaplan-Meier survival analysis confirmed this finding, with a 52.4% death rate among patients with Deltalactate greater than 100 comparatively to 84.7% when Deltalactate was less than 100 (log-rank test, P = 0.0002). An adapted response (lactate production) to a pharmacological trigger (epinephrine) is associated with better prognosis during

  7. Intra-arterial Methylprednisolone Infusion in Treatment-Resistant Graft-Versus-Host Disease

    SciTech Connect

    Weintraub, Joshua L. Belanger, Adam R.; Sung, Chris C.; Stangl, P. Anondo; Nowakowski, F. Scott; Lookstein, Robert L.

    2010-06-15

    Acute graft-versus-host disease (GVHD) is a potentially fatal complication following allogeneic hematopoietic stem cell transplant. Standard primary therapy for acute GVHD includes systemic steroids, often in combination with other agents. Unfortunately, primary treatment failure is common and carries a high mortality. There is no generally accepted secondary therapy for acute GVHD. Although few data on localized therapy for GVHD have been published, intra-arterial injection of high-dose corticosteroids may be a viable option. We treated 11 patients with steroid-resistant GVHD using a single administration of intra-arterial high-dose methylprednisolone. Three patients (27%) died periprocedurally. Four patients (36%) had a partial response to intra-arterial treatment and were discharged on total parenteral nutrition and oral medication. Four patients (36%) had a complete response and were discharged on oral diet and oral medication. No immediate treatment or procedure-related complications were noted. Twenty-seven percent of patients survived long-term. Our preliminary results suggest that regional intra-arterial treatment of steroid-resistant GVHD is a safe and potentially viable secondary therapy in primary treatment-resistant GVHD.

  8. VASCULAR LESIONS AND S-THROMBOMODULIN CONCENTRATIONS FROM AURICULAR ARTERIES OF RABBITS INFUSED WITH MICROBUBBLE CONTRAST AGENT AND EXPOSED TO PULSED ULTRASOUND

    PubMed Central

    Zachary, James F.; Blue, James P.; Miller, Rita J.; O’Brien, William D.

    2007-01-01

    Arterial injury resulting from the interaction of contrast agent (CA) with ultrasound (US) was studied in rabbit auricular arteries and assessed by histopathologic evaluation and s-thrombomodulin concentrations. Three sites on each artery were exposed (2.8 MHz, 5-min exposure duration, 10-Hz pulse repetition frequency, 1.4-μs pulse duration) using one of three in situ peak rarefactional pressures (0.85, 3.9 or 9.5 MPa). Saline, saline/CA, and saline/US infusion groups (n = 28) did not have histopathologic damage. The saline/CA/US infusion group (n = 10) at exposure conditions below the FDA mechanical index limit of 1.9 did not have histopathologic damage, whereas the saline/CA/US infusion group (n = 9) at exposure conditions above the FDA limit did have damage (5 of 9 arteries). Lesions were characteristic of acute coagulative necrosis. Mean s-thrombomodulin concentrations, a marker for endothelial cell injury, were highest in rabbits exposed to US at 0.85 and 3.9 MPa, suggesting that vascular injury may be physiological and not accompanied by irreversible cellular injury. PMID:17112964

  9. [Case of continuous trans-arterial calcium gluconate infusion using a direct arterial sphygmomanometry line that exhibited dramatic improvement of chemical burns on the fingers caused by hydrofluoric acid].

    PubMed

    Miyamoto, Kazuyuki; Shimizu, Makiko; Tanaka, Kotaro; Minemura, Atsuko; Tamatsukuri, Tatsuro; Miyake, Yasufumi; Aruga, Tohru

    2014-12-01

    Hydrofluoric acid (HFA) is commonly used and many injuries occur on the upper extremities following exposure to HFA. The use of calcium gluconate (CG) -containing gel or local injections of CG are widely used for the initial treatment of HFA exposure. However, severe pain continues in some cases despite the treatment. There was a report that trans-arterial CG infusion could improve HFA burns, however, such treatment is not an established clinical procedure. A 30-year-old male presented at our hospital with severe pain in his left thumb. He had been cleaning tiles with an HFA-containing detergent. We diagnosed him with a chemical burn due to HFA exposure. Local CG injections were tried several times, but his terrible pain continued. Therefore, a direct arterial sphygmomanometry line was inserted from the left radial artery, and continuous transarterial CG injection was performed. His terrible pain dramatically improved. Direct arterial sphygmomanometry systems are widely used in the critical care field to monitor the hemodynamics and ICU staffs are used to dealing with it. Moreover, continuous saline infusion prevents the tube obstruction. Continuous CG infusion from a direct arterial sphygmomanometry line is simple and safe way to administer CG in HFA burns.

  10. [The accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with adenosine triphosphate disodium (ATP) infusion in the diagnosis of coronary artery disease].

    PubMed

    Kinoshita, S; Suzuki, S; Shindou, A; Watanabe, K; Muramatsu, T; Ide, M; Dohi, Y; Yamashita, S; Suzuki, T; Nishimura, K

    1994-08-01

    The diagnostic accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with ATP infusion were studied in 172 patients with or without coronary artery disease. ATP was infused for five minutes at a rate of 0.16 mg/kg/min (group A) or 0.18 mg/kg/min (group B) via antecubital vein. One hundred and eleven (67 of group A, 44 of group B) of 172 patients underwent coronary arteriography (CAG). In 111 patients received CAG, overall sensitivity, specificity and accuracy of this method were 88%, 84% and 87%, respectively. In 67 patients of group A, these were 92%, 81% and 90%. In 44 patients of group B, 79%, 87% and 82% were documented (NS, between group A and B). Chest pain, flushing, bradycardia and ST depression were included in side effects caused by ATP infusion. At least one of these side effects were observed in 84% of the all 172 patients, 89% of group A and 75% of group B (NS). But, all of the side effects were spontaneously alleviated within two minutes without any therapy. In conclusion, pharmacologic stress myocardial scintigraphy with ATP infusion is very accurate and safe, and infusion rate of 0.16 mg/kg/min is optimal for this purpose. PMID:7933682

  11. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial

    PubMed Central

    Ikeda, M.; Shimizu, S.; Sato, T.; Morimoto, M.; Kojima, Y.; Inaba, Y.; Hagihara, A.; Kudo, M.; Nakamori, S.; Kaneko, S.; Sugimoto, R.; Tahara, T.; Ohmura, T.; Yasui, K.; Sato, K.; Ishii, H.; Furuse, J.; Okusaka, T.

    2016-01-01

    Background Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. Patients and methods We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5–7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4–6 weeks) or Sor (400 mg bid). The primary end point was overall survival. Results A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38–0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. Conclusion SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. Clinical Trial registration UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703. PMID:27573564

  12. Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Kaneyasu, Yuko Nagai, Nobutaka; Nagata, Yasushi; Hashimoto, Yasutoshi; Yuki, Shintaro; Murakami, Yuji; Kenjo, Masahiro; Kakizawa, Hideaki; Toyota, Naoyuki; Fujiwara, Hisaya; Kudo, Yoshiki; Ito, Katsuhide

    2009-10-01

    Purpose: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. Materials and Methods: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with {sup 192}Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. Results: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade {>=}3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade {>=}3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade {>=}3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. Conclusion: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

  13. Time courses of PIVKA-II and AFP levels after hepatic artery embolization and hepatic artery infusion against hepatocellular carcinoma: relation between the time course and tumor necrosis.

    PubMed

    Kishi, K; Sonomura, T; Mitsuzane, K; Nishida, N; Kimura, M; Satoh, M; Yamada, R; Kodama, N; Kinoshita, M; Tanaka, H

    1992-01-01

    We examined 35 untreated patients with unresectable hepatocellular carcinoma who exhibited positivity for both plasma PIVKA-II and serum AFP, and studied the weekly course of these markers from the pre-TAE or -HAI period to the third week of treatment. We correlated changes in these markers with the tumor necrosis rate and the time course on X-ray CT images. One week after TAE, the tumor necrosis rate and the time course of PIVKA-II showed a significant correlation (r = 0.7), while the correlation was between the time course of AFP and the tumor necrosis rate was insignificant (r = 0.2). At two and three weeks after TAE, both the time course of AFP and PIVKA-II showed significant correlations with the tumor necrosis rate. In 16 patients with tumor necrosis rates of not less than 90%, the mean of the actual half-life (AHL) of PIVKA-II was 3.2 days, the shortest was 1.83 days, and 75% of all AHLs clustered from two days to four days, while the mean and shortest AHLs of AFP were six days and 2.98 days, respectively, exhibiting a broader distribution. On the other hand, in three out of the nine cases of hepatocellular carcinoma complicated with portal tumor thrombi, PIVKA-II increased after HAI in spite of a reduction in tumor size. It was suggested that the PIVKA-II level requires careful interpretation in cases of portal vein obstruction after intensive hepatic arterial infusion of anticancer agents.

  14. Effect of dietary nitrogen content and intravenous urea infusion on ruminal and portal-drained visceral extraction of arterial urea in lactating Holstein cows.

    PubMed

    Kristensen, N B; Storm, A C; Larsen, M

    2010-06-01

    Urea extraction across ruminal and portal-drained visceral (PDV) tissues were investigated using 9 rumen-cannulated and multi-catheterized lactating dairy cows adapted to low-N (12.9% crude protein) and high-N (17.1% crude protein) diets in a crossover design. The interaction between adaptation to dietary treatments and blood plasma concentrations of urea was studied by dividing samplings into a 2.5-h period without urea infusion followed by a 2.5-h period with primed continuous intravenous infusion of urea (0.493+/-0.012 mmol/kg of BW per h). Cows were sampled at 66+/-14 and 68+/-12 d in milk and produced 42+/-1 and 36+/-1 kg of milk/d with the high-N and low-N diets, respectively. The arterial blood urea concentration before urea infusion was 1.37 and 4.09+/-0.18 mmol/L with low-N and high-N, respectively. Dietary treatment did not affect the urea infusion-induced increase in arterial urea concentration (1.91+/-0.13 mmol/L). Arterial urea extraction across the PDV and rumen increased from 2.7 to 5.4+/-0.5% and from 7.1 to 23.8+/-2.1% when cows were changed from high-N to low-N, respectively. Urea infusion did not decrease urea extractions, implying that urea transport rates were proportional to arterial urea concentrations. Urea extraction increased more across the rumen wall than across the total PDV for low-N compared with high-N, which implies that a larger proportion of total PDV uptake of arterial urea is directed toward the rumen with decreasing N intake. The ruminal vein - arterial (RA) concentration difference for ammonia increased instantly (first sampling 15 min after initiation of infusion) to the primed intravenous infusion when cows were adapted to the low-N diet. The RA difference for ammonia correlated poorly to the ventral ruminal concentration of ammonia (r=0.55). Relating the RA difference for ammonia to a function of both ruminal ammonia concentration and the RA difference for urea markedly improved the fit (r=0.85), indicating that a large

  15. The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs

    PubMed Central

    Jin, Hongting; Xu, Taotao; Chen, Qiqing; Wu, Chengliang; Wang, Pinger; Mao, Qiang; Zhang, Shanxing; Shen, Jiayi; Tong, Peijian

    2016-01-01

    This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs) could treat osteonecrosis of the femoral head (ONFH) and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of the femoral heads was significantly reduced in MSCs group. Moreover, the trabecular bone volume was increased and the empty lacunae rate was decreased in MSCs group. In addition, the BrdU-positive MSCs were unevenly distributed in femoral heads and various vital organs. But no obvious abnormalities were observed. Furthermore, most of BrdU-positive MSCs in necrotic region expressed osteocalcin in MSCs group and a few expressed peroxisome proliferator-activated receptor-γ (PPAR-γ). Taken together, these data indicated that intra-arterially infused MSCs could migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. It suggests that intra-arterial infusion of autologous MSCs might be a feasible and relatively safe method for the treatment of femoral head necrosis. PMID:26779265

  16. Differential Clearance of Rat and Human Bone Marrow-Derived Mesenchymal Stem Cells From the Brain After Intra-arterial Infusion in Rats.

    PubMed

    Khabbal, Joonas; Kerkelä, Erja; Mitkari, Bhimashankar; Raki, Mari; Nystedt, Johanna; Mikkonen, Ville; Bergström, Kim; Laitinen, Saara; Korhonen, Matti; Jolkkonen, Jukka

    2015-01-01

    Intra-arterial (IA) delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) has shown potential as a minimally invasive therapeutic approach for stroke. The aim of the present study was to determine the whole-body biodistribution and clearance of technetium-99m ((99m)Tc)-labeled rat and human BM-MSCs after IA delivery in a rat model of transient middle cerebral artery occlusion (MCAO) using single-photon emission computed tomography (SPECT). Our hypothesis was that xenotransplantation has a major impact on the behavior of cells. Male RccHan:Wistar rats were subjected to sham operation or MCAO. Twenty-four hours after surgery, BM-MSCs (2 × 10(6) cells/animal) labeled with (99m)Tc were infused into the external carotid artery. Whole-body SPECT images were acquired 20 min, 3 h, and 6 h postinjection, after which rats were sacrificed, and organs were collected and weighed for measurement of radioactivity. The results showed that the majority of the cells were located in the brain and especially in the ipsilateral hemisphere immediately after cell infusion both in sham-operated and MCAO rats. This was followed by fast disappearance, particularly in the case of human cells. At the same time, the radioactivity signal increased in the spleen, kidney, and liver, the organs responsible for destroying cells. Further studies are needed to demonstrate whether differential cell behavior has any functional impact.

  17. The effect of milrinone infusion on right ventricular function during coronary anastomosis and early outcomes in patients undergoing off-pump coronary artery bypass surgery

    PubMed Central

    Jo, Hyong Rae; Lee, Woo Kyung; Kim, Yong Ho; Min, Jin Hye; Chae, Young Keun; Choi, In Gyu; Kim, Young Sin

    2010-01-01

    Background During coronary anastomosis in off-pump coronary artery bypass surgery (OPCAB), hemodynamic alternations can be induced by impaired diastolic function of the right ventricle. This study was designed to examine the effect of milrinone on right ventricular function and early outcomes in patients undergoing OPCAB. Methods Forty patients undergoing OPCAB were randomly assigned in a double-blind manner to receive either milrinone (milrinone group, n = 20) or normal saline (control group, n = 20). Hemodynamic variables were measured after pericardiotomy (T1), 5 min after stabilizer application for anastomosis of the left anterior descending coronary artery (LAD, T2), the obtuse marginalis branch (OM, T3), the right coronary artery (RCA, T4), 5 min after sternal closure (T5), and after ICU arrival. The right ventricular ejection fraction (RVEF) and right ventricular volumetric parameters were also measured using the thermodilution technique. For evaluation of early outcomes, the 30-day operative mortality and morbidity risk models were used. Results There was no significant difference in hemodynamic variables, including mean arterial pressure, between the 2 groups, except for the cardiac index and RVEF. The cardiac index and RVEF were significantly greater at T3 in the milrinone group than in the control group. Conclusions Continuous infusion of milrinone demonstrated a beneficial effect on cardiac output and right ventricular function in patients undergoing OPCAB, especially during anastomosis of the graft to the OM artery, and it had no adverse effect on early outcomes. PMID:20740213

  18. Evaluation of the internal thoracic arterial graft patency by the transthoracic Doppler method under continuous intravenous infusion of adenosine triphosphate disodium.

    PubMed

    Fukata, Y; Horike, K; Fujimoto, E; Shimoe, Y; Kanbara, T

    1999-10-01

    Usefulness of the Doppler method under continuous infusion of adenosine triphosphate disodium (ATP) for improvement of accuracy in the diagnosis of the left internal thoracic arterial graft (LITA) patency was examined using transthoracic ultrasonic echocardiography. 1) Influence of ATP on the Doppler velocity in a graft was examined in 7 patients with good LITA grafts using physiological saline as the control. In the ATP group, 80 mg of ATP was dissolved in 20 ml physiological saline and continuously infused at 0.14 mg/kg/min. In the saline group, an equal volume of physiological saline was administered and the blood flow velocity in the LITA was recorded continuously by the transthoracic Doppler method from the supraclavicular fossa approach. Results; ATP administration increased the blood flow velocity in the LITA and the rate of increase was 48.3% for systolic peak velocity, 111% for diastolic peak velocity, 64.4% for systolic time velocity integral and 99% for diastolic time velocity integral indicating particularly high rates of increase in diastolic components. The diastolic/systolic peak velocity ratio or diastolic fraction did not increase significantly. In the saline group, none of the parameters showed a change. 2) Angiographic findings of the LITA were compared with the measurement values of the diastolic components by the Doppler method to examine usefulness of diastolic component measurement with ATP infusion for diagnosis of LITA patency. Subjects were 19 patients with good LITA (group A) and 8 patients with bad LITA (group B). Results; while there were significant differences in the mean baseline diastolic peak velocity, mean diastolic time velocity integral and mean diastolic fraction between the groups, overlapping was seen in individual cases. However, the inter-group differences were more distinct by ATP infusion and the borderline values were 30 cm/sec for diastolic peak velocity and 10 for diastolic time velocity integral. 3) Reliability of the

  19. Development of immunoassays for human urokinase

    NASA Technical Reports Server (NTRS)

    Atassi, M. Zouhair

    1988-01-01

    Radioimmune assays (RIA) and enzyme linked immune assays for measurement of pro-urokinase and the two active forms of the enzyme were developed. Polyclonal and monoclonal antibodies, with desired specificities against preselected synthetic regions of urokinase (UK), were obtained by immunization with the respective synthetic peptides and used to develop RIA for zymogen and the two activated forms of UK.

  20. Hepatic Arterial Infusion Chemotherapy Using Fluorouracil Followed by Systemic Therapy Using Oxaliplatin Plus Fluorouracil and Leucovorin for Patients with Unresectable Liver Metastases from Colorectal Cancer

    SciTech Connect

    Seki, Hiroshi Ozaki, Toshirou; Shiina, Makoto

    2009-07-15

    The purpose of this study was to assess retrospectively the sequential treatment of hepatic arterial infusion (HAI) chemotherapy followed by systemic therapy using oxaliplatin plus 5-flourouracil (5-FU) and leucovorin, namely, FOLFOX, for patients with liver metastases from colorectal cancer. We reviewed 20 patients with unresectable liver metastases from colorectal cancer. Patients were initially treated with HAI chemotherapy until disease progression (5-fluorouracil, 1000 mg/m{sup 2} intra-arterial infusion, weekly) and then with FOLFOX thereafter (FOLFOX4, n = 13; modified FOLFOX6, n = 7). Adverse events, tumor response, and time to progression for each therapy were evaluated retrospectively, and overall survival was estimated. Toxicity of HAI chemotherapy was generally mild. Of 20 patients, adverse events leading to treatment discontinuation occurred in only 1 patient (5%) during initial therapy using HAI chemotherapy, while 9 patients (45%) exhibited adverse events during subsequent FOLFOX therapy. For HAI chemotherapy and FOLFOX, objective response rates were 85.0% and 35.0%, respectively, and median time to progression was 11.6 and 5.1 months, respectively. Median overall survival was 30.1 months. In conclusion, the sequence of HAI chemotherapy followed by FOLFOX is a promising treatment strategy for the long-term use of active chemotherapeutic agents, leading to a superior tumor response and fewer toxic effects in patients with unresectable liver metastases from colorectal cancer.

  1. [A long-surviving patient with Stage IV breast cancer with no recurrence after combined therapy of medroxy progesterone acetate (MPA) and intra-arterial infusion chemotherapy].

    PubMed

    Yamada, Takeshi; Yuyama, Yuichi; Okazaki, Yutaka

    2004-09-01

    The patient is a 42-year-old woman who had advanced (Stage IV) right breast cancer with contralateral supraclavicular lymph node metastasis. She was treated with the combined use of MPA and the intra-arterial infusion chemotherapy. We administered EPI into the left subclavian artery and the right internal thoracic artery. Total dose of EPI was 210 mg. MPA was administered po at 1,200 mg/day daily. During the chemotherapy, she experienced only grade 2 alopecia. After the chemotherapy, the regressive change was noted in the primary lesion. The clinical response was evaluated CR. She underwent right modified mastectomy and the resection of contralateral supraclavicular lymph nodes. Although the clinical response was very good, the pathological effect was only Grade 1b. Eight years have passed since the operation, and the patient is still alive with no sign of recurrence. It is suggested that this combination therapy may be useful for advanced breast cancer and the like. PMID:15446562

  2. IT infusion

    NASA Technical Reports Server (NTRS)

    Feather, M. S.

    2002-01-01

    Infusing IT technology is a perennial challenge. The Technology Infusion and Maturity Assessment approach of Cornford & Hicks is shown applied to an example of IT infusion: moedl-based V&V of spacecraft software.

  3. Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma

    SciTech Connect

    Martinez, A.; Goffinet, D.R.; Donaldson, S.S.; Bagshaw, M.A.; Kaplan, H.S.

    1985-01-01

    Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients - of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, the authors believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma.

  4. Central venous line complications with chronic ambulatory infusion of prostacyclin analogues in pediatric patients with pulmonary arterial hypertension

    PubMed Central

    Mullen, Mary P.

    2015-01-01

    Abstract Chronic infusion of prostacyclin (PGI2) via a Broviac central venous line (CVL) is attended by risk of CVL-related complications, but we know of only one report regarding CVL-associated bloodstream infection (BSI) with PGI2 in children and none regarding other complications. We conducted a retrospective cohort study involving pediatric patients with pulmonary hypertension treated with chronic intravenous infusion of PGI2 at Boston Children’s Hospital and determined the rate (per 1,000 line-days) of various CVL-related complications. We also determined how often complications necessitated line replacement and hospitalization, time to replacement of CVLs, and interpatient variability in the incidence of complications. From 1999 until 2014, 26 patients meeting follow-up criteria had PGI2 infusion, representing 43,855 line-days; mean follow-up was 56 months (range, 1.4–161 months). The CVL complication rates (per 1,000 line-days) were as follows: CVL-BSI, 0.25; superficial line infection, 0.48; impaired integrity, 0.59; occlusion, 0.09; and malposition, 0.32. The total complication rate was 1.73 cases per 1,000 line-days. All CVL-BSI and malposition cases were treated with CVL removal and replacement. Of CVLs with impaired integrity, 23 could be repaired and 3 required replacement. Six of 21 superficial CVL infections required replacement of the CVL. Three of 4 occluded CVLs were replaced. CVL complications occasioned 65 hospitalizations. There was marked interpatient variability in the rate of complications, much but not all of which appeared to be related to duration of CVL placement. We conclude that non-BSI complications are very significant and that efforts to teach and emphasize other aspects of line care are therefore very important. PMID:26064457

  5. Clinical Application of a New Indwelling Catheter with a Side-Hole and Spirally Arranged Shape-Memory Alloy for Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Yagihashi, Kunihiro Takizawa, Kenji; Ogawa, Yukihisa; Okamoto, Kyoko; Yoshimatsu, Misako; Fujikawa, Atsuko; Shimamoto, Hiroshi; Nakajima, Yasuo

    2010-12-15

    A new indwelling catheter, G-spiral (GSP), was developed for hepatic arterial infusion chemotherapy (HAIC) by way of an implanted catheter-port system (CPS). Here we evaluated its physical properties and the outcomes of its clinical use. The GSP vessel-fixing power and its ability to follow a guidewire were determined with a vascular in vitro model, and Student t test was used to determine statistical significance (P < 0.05). A retrospective analysis was performed to evaluate the technical success rate and to identify the clinical complications associated with radiologic CPS implantation with GSP in 65 patients with unresectable hepatic tumors. The mean vessel-fixing power of the GSP (14.4 g) significantly differed from that of a GSP with a cut shape-memory alloy (3.3 g). The mean resistance to following the guidewire displayed by the GSP (88.5 g) was significantly less than that for a 5F W-spiral (106.3 g) or 4F Cobra-type angiographic catheter (117.8 g). The CPS was placed successfully in 64 of 65 cases (98.5%). Hepatic artery occlusion was observed in one case. Occlusion, cracking, and infection of CPS were observed in one, two, and one case, respectively. The GSP is a highly useful indwelling catheter that can be used for HAIC.

  6. [Recurrence and survival rate of advanced gastric cancer after preoperative EAP-II intra-arterial infusion therapy].

    PubMed

    Masuyama, M; Taniguchi, H; Takeuchi, K; Miyata, K; Koyama, H; Tanaka, H; Higashida, T; Koishi, Y; Mugitani, T; Yamaguchi, T

    1994-09-01

    Ninety-eight patients with advanced gastric cancers underwent gastrectomy from Jan. 1989 to Dec. 1991. For these patients, preoperative intra-arterial injection therapy using EAP-II (etoposide 100 mg, epirubicin 20 mg, carboplatin 100 mg) was given to 24 patients. In this report, the recurrence and survival rate of these patients were investigated. After curative resection, the survival rate of patients with EAP-II 36 months after operation was 76.9%, while that of patients without EAP-II was 78.6%. There were no significant differences between these two groups. Two peritoneal carcinomatoses and two liver metastases were seen in patients with EAP-II (recurrence rate, 30.7%). Eight recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination, 4; local recurrence, 3; lymph node recurrence, 1). Previously, we reported that drugs were remarkably accumulated in gastric cancer tissue and regional lymph nodes after EAP-II intra-arterial injection therapy. This high accumulation might cause no local or lymph node recurrence was seen in patient with EAP-II. Thus, it was concluded that preoperative EAP-II intra-arterial injection may prevent local and lymph node recurrences, and that further study of the combination and dose of anti-cancer drug needed to improve the postoperative survival rate in advanced gastric cancer patients.

  7. Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion.

    PubMed

    Zhao, Haiping; Wang, Rongliang; Wu, Xiaoning; Liang, Jia; Qi, Zhifeng; Liu, Xiangrong; Min, Lianqiu; Ji, Xunming; Luo, Yumin

    2015-03-01

    Local infusion of low dose erythropoietin (EPO) alleviates cerebral ischemia and reperfusion (I/R) injury in rats; however, the underlying molecular mechanisms are still unclear. The present study investigated the effect of low dose EPO treatment on I/R-induced endoplasmic reticulum (ER) stress in brain tissue and isolated microvessels in rodents. Sprague-Dawley rats were subjected to 2 h ischemia/24 h reperfusion by middle cerebral artery (MCA) occlusion, then administered fluorescein isothiocyanate-labeled EPO via MCA infusion (MCAI) or subcutaneous injection (SI) to compare the efficiency of two modes of delivery. Neurobehavioral deficits and infarct volume, and the expression of ER stress-associated proteins and apoptosis in brain tissue or isolated microvessels, as well as the transcriptional activity of 16 factors involved in ER stress and the unfolded protein response in brain tissue was asscessed. A higher EPO level in cerebrospinal fluid and brain tissue was observed in rats treated with EPO by MCAI (800 IU/kg) than by SI (5000 IU/kg). Moreover, neurobehavioral deficits and infarct volume were reduced in rats treated with EPO by MCAI and salubrinal. EPO suppressed the expression of ER stress signals glucose-regulated protein 78, activating transcription factor (ATF) 6α, and CCAAT enhancer-binding protein homologous protein (CHOP), as well as that of the pro-apoptotic protein caspase-3 in brain microvessels, and decreased the number of CHOP-positive, apoptotic neurons. EPO treatment also reduced the transcriptional activities of CHOP, forkhead box protein O1, and ATF4. These results provide evidence that low dose EPO treatment via MCAI provides neuroprotection following acute ischemic stroke by inhibiting the ER stress response. PMID:25626440

  8. Infusion Extractor

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R.

    1988-01-01

    Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

  9. Mitomycin-based hepatic arterial infusion chemotherapy for solitary ampullary cancer liver metastasis: an unusual treatment for an uncommon disease.

    PubMed

    Vitale, Felice V; Romeo, Placido; Luciani, Bruno; Raffaele, Mario; Colina, Paolo; Ferraù, Francesco

    2015-10-01

    Ampullary carcinoma is an uncommon gastrointestinal disease. Its natural history is often characterized by the occurrence of liver metastases. Among patients who undergo pancreatoduodenectomy, those presenting with lymph nodes involvement are more prone to early distant disease relapse. In this report, a patient previously diagnosed with ampullary carcinoma had been treated with curative surgery. After subsequent adjuvant gemcitabine, the patient developed significant myelotoxicity and suffered from a single liver metastasis a few months later. A hepatic intra-arterial mitomycin plus fluorouracil-based chemotherapy was administered in order to avoid any serious systemic toxicity. The treatment was well tolerated and no serious side effects occurred. Extra-hepatic cancer relapse, involving intra-thoracic and abdominal lymph nodes, was observed not long after the initial intra-hepatic almost complete response. In conclusion, the locoregional chemotherapy administration was effective in overcoming any systemic toxicities and showed activity against the liver metastasis but it did not prevent extra-hepatic cancer dissemination.

  10. Early Detection of Therapeutic Response to Hepatic Arterial Infusion Chemotherapy of Liver Metastases from Colorectal Cancer Using Diffusion-Weighted MR Imaging

    SciTech Connect

    Marugami, Nagaaki; Tanaka, Toshihiro Kitano, Satoru; Hirohashi, Shinji; Nishiofuku, Hideyuki; Takahashi, Aki; Sakaguchi, Hiroshi; Matsuoka, Masaki; Otsuji, Toshio; Takahama, Junko; Higashiura, Wataru; Kichikawa, Kimihiko

    2009-07-15

    The purpose of this study was to investigate whether diffusion-weighted magnetic resonance imaging (DWI) is useful for early detection of the response of hepatic colorectal metastases to hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil (5-FU). The subjects were 12 patients with hepatic colorectal metastases. The indwelling catheter for HAIC was placed in the hepatic artery, and 1000 mg/m{sup 2} 5-FU was given repeatedly once a week. DWI was performed before and 9 days after HAIC. The minimum and mean apparent diffusion coefficient (ADC) values (minADC and meanADC) were measured. The relative change in ADC values (%ADC) and the relative change in tumor size on follow-up CT after 3 months (reduction ratio) were determined. Liver metastases were divided into two groups, responder and nonresponder. The correlation between %ADC and reduction ratio was determined, and %ADC was compared between the two groups. Eleven patients successfully completed HAIC over the 3-month period; 48 metastatic lesions were evaluated. Positive correlations were observed for relative change between %minADC and reduction ratio (r = 0.709) and between %meanADC and reduction ratio (r = 0.536). Both %minADC and %meanADC were significantly greater in the responder group than in the nonresponder group. With the threshold determined as < 3.5%, the receiver-operating curve analysis showed higher sensitivity and specificity values for %minADC (100% and 92.6%, respectively) than for %meanADC (66.7% and 74.1%, respectively). In conclusion, the relative change in minimum ADC values on DWI may be useful for early detection of the response of liver metastases to HAIC with 5-FU.

  11. Combined Arterial Infusion and Stent Implantation Compared with Metal Stent Alone in Treatment of Malignant Gastroduodenal Obstruction

    SciTech Connect

    Wang Zhongmin; Chen Kemin; Gong Ju; Zheng Yunfeng; Wang Tianxiang

    2009-09-15

    Many patients with malignant gastroduodenal obstruction have an unresectable primary lesion and distant metastases, which may prompt palliative management to allow the patient to eat and to improve the quality of life. Intraluminal metallic stent implantation (MSI) under fluoroscopic guidance has been reported to be an effective option for symptomatic relief in these patients, with a good safety record. An alternative, dual interventional therapy (DIT), has been used during the last decade, in which prosthesis insertion is followed by intra-arterial chemotherapy via the tumor-feeding arteries. The aim of this study was to compare success rates, complication rates, and survival time between MSI and DIT in patients who presented with gastroduodenal obstruction from advanced upper gastrointestinal tract cancer. All consecutive patients with malignant gastroduodenal obstruction seen at our center between October 2002 and August 2007 were retrospectively studied. Patients were treated palliatively by either MSI or DIT by the patient's or the next of kin's decision. Outcomes included technical and clinical success, complication rates, and survival. Of the 164 patients with malignant gastric and duodenal outlet obstructions, 80 (49%) underwent stent insertion as the primary therapy, while the remaining 84 (51%) received DIT. Clinical characteristics were similar between the two groups. In the MSI cohort initial stent implantation was successful in 73 patients (91%), two stents were used in 5 patients, and delayed additional stent insertion for stent obstruction related to tumor overgrowth was required in 3 patients during follow-up. In the DIT cohort the technical success rate was 94%, 3 patients required two stents, and stent obstruction occurred in 2 patients after initial stent placement. Early postprocedural clinical success, indicated by average dysphagia score, improved significantly in both groups: MSI group, from 4.56 to 1.51 (P < 0.01); and DIT group, from 4

  12. Infusion extractor

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R. (Inventor)

    1986-01-01

    This invention relates to an apparatus and method of removing desirable constituents from an infusible material by infusion extraction. A piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber. The method is applicable to operation in low or micro-gravity environments.

  13. Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver

    PubMed Central

    Said, Rabih; Kurzrock, Razelle; Naing, Aung; Hong, David S.; Fu, Siqing; Piha-Paul, Sarina; Wheler, Jennifer J; Janku, Filip; Kee, Bryan K; Bidyasar, Savita; Lim, Joann; Wallace, Michael; Tsimberidou, Apostolia M.

    2015-01-01

    BACKGROUND Liver metastases are associated with a poor prognosis. We investigated the use of hepatic arterial infusion (HAI) of irinotecan combination therapy in patients with liver metastases. PATIENTS AND METHODS Patients with histologically confirmed advanced cancer with liver metastases that was refractory to standard therapy were eligible. A standard “3+3” phase I study design was used to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Three cohorts were evaluated: HAI of irinotecan with systemic intravenous (IV) (a) bevacizumab, (b) oxaliplatin and bevacizumab, or (c) bevacizumab and cetuximab. RESULTS From October 2009 through December 2013, 98 patients with various tumor types were enrolled (median age, 62 years, range, 34–85; and median number of prior therapies, 4, range, 1–11). In cohorts A and C, dose escalation continued until the highest dose level—considered the MTD—was reached. In cohort B, dose escalation continued until dose level 3, and dose level 2 was considered the MTD. Rates of grade 3/4 adverse events were as follows: diarrhea, 8%; fatigue, 4%; neutropenia, 4%; thrombocytopenia, 2%; and skin rash, 2%. Seventy-seven patients were evaluable for response. Partial response was noted in 5 (6.5%) patients (neuroendocrine cancer, n=2; CRC, n=2; NSCLC, n=1); and stable disease ≥ 6 months in 17 (22.1%) patients (CRC, n=13; breast, n=1; neuroendocrine, n=1; NSCLC, n=1; pancreatic, n=1). CONCLUSIONS HAI irinotecan in combination with bevacizumab; oxaliplatin plus bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option for selected patients with advanced cancer and liver involvement. PMID:25990659

  14. Quantitative method of measuring cancer cell urokinase and metastatic potential

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R. (Inventor)

    1993-01-01

    The metastatic potential of tumors can be evaluated by the quantitative detection of urokinase and DNA. The cell sample selected for examination is analyzed for the presence of high levels of urokinase and abnormal DNA using analytical flow cytometry and digital image analysis. Other factors such as membrane associated urokinase, increased DNA synthesis rates and certain receptors can be used in the method for detection of potentially invasive tumors.

  15. Affinity chromatography for purification of two urokinases from human urine.

    PubMed

    Takahashi, R; Akiba, K; Koike, M; Noguchi, T; Ezure, Y

    2000-05-26

    A new affinity chromatography (hydrophobic-mediated affinity chromatography), which was characterized by the matrix having both affinity site to urokinase and hydrophobic site, was established for the purification of urokinase from human urine. The hydrophobic affinity matrix (tentatively named PAS in the text) was prepared by immobilizing 6-aminocaproic acid on Sepharose CL-6B, followed by a coupling p-aminobenzamidine to a part of the hydrophobic site on the matrix. The PAS matrix was applied to the purification of urokinase from human urine, and high- and low-molecular weight pure urokinases were efficiently obtained in high yield by the present method. PMID:10892585

  16. Antibodies Against Three Forms of Urokinase

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.; Atassi, M. Zouhair

    2007-01-01

    Antibodies that bind to preselected regions of the urokinase molecule have been developed. These antibodies can be used to measure small quantities of each of three molecular forms of urokinase that could be contained in microsamples or conditioned media harvested from cultures of mammalian cells. Previously available antibodies and assay techniques do not yield both clear distinctions among, and measurements of, all three forms. Urokinase is a zymogen that is synthesized in a single-chain form, called ScuPA, which is composed of 411 amino acid residues (see figure). ScuPA has very little enzyme activity, but it can be activated in two ways: (1) by cleavage of the peptide bond lysine 158/isoleucine 159 and the loss of lysine 158 to obtain the high molecular-weight (HMW) form of the enzyme or (2) by cleavage of the bond lysine 135/lysine 136 to obtain the low-molecular-weight (LMW) form of the enzyme. The antibodies in question were produced in mice and rabbits by use of peptides as immunogens. The peptides were selected to obtain antibodies that bind to regions of ScuPA that include the lysine 158/isoleucine 159 and the lysine 135/lysine 136 bonds. The antibodies include monoclonal and polyclonal ones that yield indications as to whether either of these bonds is intact. The polyclonal antibodies include ones that preferentially bind to the HMW or LMW forms of the urokinase molecule. The monoclonal antibodies include ones that discriminate between the ScuPA and the HMW form. A combination of these molecular-specific antibodies will enable simultaneous assays of the ScuPA, HMW, and LMW forms in the same specimen of culture medium.

  17. Increased Plasminogen Activator (Urokinase) in Tissue Culture After Fibrin Deposition

    PubMed Central

    Bernik, Maria B.

    1973-01-01

    Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways—affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis. PMID:4266421

  18. Characterization of a specific anti-human urokinase antibody: Development of a sensitive competition radioimmunoassay for urokinase antigen

    SciTech Connect

    Huber, K.; Kirchheimer, J.; Binder, B.R.

    1984-05-01

    Specific inhibiting IgG antibodies were raised in a rabbit using purified human high molecular weight urokinase as antigen. The antibodies reacted with both high molecular weight and low molecular weight human urokinase using an Ouchterlony double-immunodiffusion technique in such a way that one line of complete identity was obtained. Neither precipitation nor functional inhibition was observed for the tissue-type plasminogen activator. Kinetic studies with plasminogen as a natural high molecular weight substrate or the synthetic low molecular weight p-nitroanilide substrate pyro-Glu-Gly-Arg-pNA revealed, for both substrates, mainly a competitive type of inhibition for the Fab fragments of the specific anti-urokinase antibodies. This characterized anti-urokinase IgG was employed to develop a competitive radioimmunoassay, for human urokinase with /sup 125/I-labeled urokinase as tracer. In this radioimmunoassay, the lower detection limit for urokinase antigen was 10 pg/ml sample; the intrassay variation was 2.8%, and the interassay variation was 5.3%. Applying this radioimmunoassay to plasma samples obtained from healthy young volunteers, urokinase antigen could be measured in a concentration of 7.82 +/- 3.97 ng/ml for mean and 6.66 +/- 2.39 ng/ml for women (mean +/- SD).

  19. [Combination Chemotherapy Using Sorafenib and Hepatic Arterial Infusion with a Fine-Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis--A Case Report].

    PubMed

    Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Murata, Akihiro; Sakae, Masayuki; Kurihara, Shigeaki; Tashima, Tetsuzo; Deguchi, Sota; Nakai, Takashi; Kawasaki, Yasuko; Kioka, Kiyohide

    2015-11-01

    Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor-shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call®). A 57-year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call® was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call® has been performed once for 6 weeks. After performing HAIC with IA-call® 5 times, the serum levels of HCC tumor markers AFP and PIVKA-Ⅱdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease. PMID:26805203

  20. Transgenic chickens expressing human urokinase-type plasminogen activator.

    PubMed

    Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

    2013-09-01

    Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P < 0.05). The expression of huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P < 0.05). Furthermore, adult transgenic rooster showed reduced (P < 0.05) fertility, as revealed by reduced volume of semen ejaculate, sperm concentration, and sperm viability. Taken together, our data suggest that huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

  1. Transgenic chickens expressing human urokinase-type plasminogen activator.

    PubMed

    Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

    2013-09-01

    Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P < 0.05). The expression of huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P < 0.05). Furthermore, adult transgenic rooster showed reduced (P < 0.05) fertility, as revealed by reduced volume of semen ejaculate, sperm concentration, and sperm viability. Taken together, our data suggest that huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders. PMID:23960123

  2. Combination treatment of biomechanical support and targeted intra-arterial infusion of peripheral blood stem cells mobilized by granulocyte-colony stimulating factor for the osteonecrosis of the femoral head: a randomized controlled clinical trial.

    PubMed

    Mao, Qiang; Wang, Weidong; Xu, Taotao; Zhang, Shanxing; Xiao, Luwei; Chen, Di; Jin, Hongting; Tong, Peijian

    2015-04-01

    The objective of this study was to determine the benefits of combination treatment with mechanical support and targeted intra-arterial infusion of peripheral blood stem cells (PBSCs) mobilized by granulocyte-colony stimulating factor (G-CSF) via the medial circumflex femoral artery on the progression of osteonecrosis of the femoral head (ONFH). Fifty-five patients (89 hips) with early and intermediate stage ONFH were recruited and randomly assigned to combination treatment or mechanical support treatment (control group). All hips received mechanical support treatment (porous tantalum rod implantation). Then, hips in the combination treatment group were performed targeted intra-arterial infusion of PBSCs. At each follow-up, Harris hip score (HHS) and Association Research Circulation Osseous (ARCO) classification were used to evaluate the symptoms and progression of osteonecrosis. Total hip arthroplasty (THA) was assessed as an endpoint at each follow-up. At 36 months, 9 of the 41 hips (21.95%) in the control group progressed to clinical failure and underwent THA whereas only 3 of the 48 hips (6.25%) in the combination treatment group required THA (p = 0.031). Kaplan-Meier survival analysis showed a significant difference in the survival time between the two groups (log-rank test; p = 0.025). Compared to the control group, combination treatment significantly improved the HHS at 36 months (p = 0.003). At the final follow-up examination, radiological progression was noted in 13 of 41 hips (31.71%) for the control group, but in only 4 of 48 hips (8.33%) for the combination treatment group (p = 0.005). The overall collapse rates were 15.15% (5/33 hips) and 8.11% (3/37 hips) in the control and combination treatment groups, respectively. Targeted intra-arterial infusion of PBSCs is capable of enhancing the efficacy of biomechanical support in the treatment of ONFH. This clinical trial confirmed that the combination treatment might be a safe and feasible

  3. Investigation of long chain omega-3 PUFAs on arterial blood pressure, vascular reactivity and survival in angiotensin II-infused Apolipoprotein E-knockout mice.

    PubMed

    Bürgin-Maunder, Corinna S; Nataatmadja, Maria; Vella, Rebecca K; Fenning, Andrew S; Brooks, Peter R; Russell, Fraser D

    2016-02-01

    Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) decrease inflammation and oxidative stress in an angiotensin II-infused apolipoprotein E-knockout (ApoE(-/-)) mouse model of AAA. This study investigated the effects of LC n-3 PUFAs on blood pressure and vascular reactivity in fourteen angiotensin II-infused ApoE(-/-) male mice. Blood pressure was obtained using a non-invasive tail cuff method and whole blood was collected by cardiac puncture. Vascular reactivity of the thoracic aorta was assessed using wire myography and activation of endothelial nitric oxide synthase (eNOS) was determined by immunohistochemistry. A high LC n-3 PUFA diet increased the omega-3 index and reduced the n-6 to n-3 PUFA ratio. At day 10 post-infusion with angiotensin II, there was no difference in systolic blood pressure or diastolic blood pressure in mice fed the high or low n-3 PUFA diets. The high LC n-3 PUFA diet resulted in a non-significant trend for delay in time to death from abdominal aortic rupture. Vascular reactivity and eNOS activation remained unchanged in mice fed the high compared to the low LC n-3 PUFA diet. This study argues against direct improvement in vascular reactivity in ApoE(-/-) mice that were supplemented with n-3 PUFA for 8 weeks prior to infusion with angiotensin II.

  4. [Thallium-201 myocardial scintigraphy after intravenous infusion of adenosine triphosphate disodium: a preliminary study in the diagnosis of coronary artery disease].

    PubMed

    Kinoshita, S; Yamashita, S; Suzuki, T; Muramatsu, T; Ide, M; Dohi, Y; Nishimura, K; Miyamae, T

    1991-12-01

    The feasibility and safety of thallium-201 myocardial scintigraphy after the intravenous infusion of adenosine triphosphate disodium (ATP) (Adetphos, Kowa) were studied in eight patients with angina pectoris and/or old myocardial infarction. Coronary arteriography (CAG) was performed by the conventional method in all patients. ATP was infused for 5 min and thallium was injected at 3 min after the start of ATP infusion. ATP was given at 0.12 mg/min/kg in two patients (group A), 0.16 mg/min/kg in three patients (group B), 0.20 mg/min/kg in one patient (group C) and 0.28 mg/min/kg in two patients (group D). SPECT images were obtained at 10 min and 180 min after thallium injection. No significant hemodynamic changes were observed in group A and B. Severe hypotension was observed in group C and one member of group D. Chest pain was experienced by one patient in group A, two in group B, one in group C, and both of the two in group D. ST depression on the electrocardiogram (ECG) was documented in one patient each of groups B and C. In one group D patient, the study was discontinued because of complete atrioventricular block persistent for 5 beats. The correlation between thallium imaging and CAG was unclear in group A, reasonable in groups B and C, and obscure in group D because of side effects. None of the patients who developed side effects of ATP were administered sublingual nitroglycerin or intravenous aminophylline. Their symptoms or ECG changes improved spontaneously within 2 min and disappeared within 5 min after termination of infusion. In conclusion, the optimal ATP regimen for this purpose was considered to be a 5 min infusion at 0.16 mg/kg/min and this method was found to be feasible and safe. PMID:1784093

  5. Intraosseous infusion.

    PubMed

    LaRocco, Brian G; Wang, Henry E

    2003-01-01

    Establishing vascular access is vital in the resuscitation of critically-ill children and adults. Intraosseous infusion (IOI) is a viable route for providing vascular access when traditional intravenous methods cannot be accomplished. IOI is relatively easy to perform and is a standard recommended intervention for the resuscitation of both adults and children. The authors review the history, anatomy, technique, and clinical application of IOI. They also highlight the use of IOI in the prehospital setting. PMID:12710793

  6. Using urokinase to restore patency in double lumen catheters.

    PubMed

    Northsea, C

    1994-08-01

    All hemodialysis patients with temporary or permanent double lumen catheters are at risk for catheter occlusion. Clinical outcomes and cost-effectiveness of using urokinase, a thrombolytic agent, to declot occluded double lumen dialysis catheters were evaluated for 2 years. Patency was restored in 95 of 102 catheters. These data support the use of urokinase to safely and effectively restore patency, thereby extending the length of time a catheter can be used for dialysis.

  7. Effectiveness and low toxicity of hepatic artery infusion with fluorouracil and mitomycin for metastatic colorectal cancer confined to the liver. The Swiss Group for Clinical and Epidemiological Cancer Research (SAKK).

    PubMed

    Borner, M; Laffer, U; Ludwig, C; Obrist, R; Metzger, U; Aeberhard, P; Weber, W; Castiglione, M; Obrecht, J P; Brunner, K

    1990-01-01

    The usefulness of hepatic artery infusion (HAI) with floxuridine is limited by the severe biliary and hepatic toxicity of floxuridine. This prompted the SAKK to evaluate the effectiveness, toxicity and feasibility of HAI with fluorouracil (FU) and mitomycin (MMC) administered by an external portable pump. Of 28 patients treated, partial responses were obtained in 14 (50%, 95% confidence interval: 30% to 70%) and stabilization in 11 (39%, 21% to 60%), for a median duration of 12.6+ months. Median survival was 19.5+ months. Grade I-II toxicity (WHO) consisted of nausea (46%), leucopenia (32%) thrombocytopenia (21%) and abdominal discomfort (25%). Two patients developed gastro-duodenal ulcers and two others grade III leucopenia. No life-threatening side effects, especially no sclerosing cholangitis or chemical hepatitis, were observed. In conclusion, HAI with FU and MMC is a valid alternative to floxuridine HAI in metastatic colorectal cancer confined to the liver.

  8. Interaction of urokinase A chain with the receptor of human keratinocytes stimulates release of urokinase-like plasminogen activator

    SciTech Connect

    Fibbi, G.; Magnelli, L.; Pucci, M.; Del Rosso, M. )

    1990-03-01

    On the basis of a fibrinolytic assay with {sup 125}I-fibrin, zymography, and immunoprobing with anti-human urokinase antibody, the authors have observed that the in vitro established NCTC human keratinocyte cell line releases into the culture medium a 54,000-Da plasminogen activator which is indistinguishable from human urokinase. Only the early release following the washing of keratinocyte monolayers is accounted for by secretion of preformed enzyme, while late secretory events require the de novo synthesis of urokinase. The released enzyme can interact by autocriny with its own receptor present on keratinocytes. The addition to the keratinocyte culture medium of the urokinase A chain can stimulate a concentration-dependent urokinase oversecretion, which is not paralleled by oversecretion of plasminogen activator inhibitor-1. Since stimulation of urokinase production can be obtained by an A chain concentration which was previously shown to be efficient in inducing keratinocyte mobilization in an in vitro migration model system, they hypothesize that this mechanism may be important in vivo during the process of wound repair.

  9. Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen)

    PubMed Central

    Lorenz, M; Müller, H H; Schramm, H; Gassel, H J; Rau, H G; Ridwelski, K; Hauss, J; Stieger, R; Jauch, K W; Bechstein, W O; Encke, A

    1998-01-01

    OBJECTIVE: To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases. METHODS: Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only. RESULTS: The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients. CONCLUSION: According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was

  10. [Continuous-infusion ketamine].

    PubMed

    Mancini, P G; Caggese, G; Di Fabio, A; Di Nino, G F; Cocchi, V

    1980-08-01

    An investigation was made of the employment of ketamin as the sole anaesthetic in general surgery, using continuous infusion of a 1% solution for both induction and maintenance in 118 cases. ECG was monitored and arterial pressure was measured invasively. Central venous pressure was also determined in 10 cases. Changes in serum enzyme values during and after surgery were examined in 35 patients. Blood samples were withdrawn before induction, after the return to consciousness, and 24 hr after the operation. Side-effects were common, but slight. Five patients suffered from nightmares, but these were persons with marked imaginative activity and a melancholic nature. Cardiocirculatory function was satisfactory. In particular, peripheral perfusion was excellent in all cases.

  11. A single infusion of MDCO-216 (ApoA-1 Milano/POPC) increases ABCA1-mediated cholesterol efflux and pre-beta 1 HDL in healthy volunteers and patients with stable coronary artery disease

    PubMed Central

    Kallend, D.G.; Reijers, J.A.A.; Bellibas, S.E.; Bobillier, A.; Kempen, H.; Burggraaf, J.; Moerland, M.; Wijngaard, P.L.J.

    2016-01-01

    Aims Apolipoprotein A-1 (ApoA-1), based on epidemiology, is inversely associated with cardiovascular (CV) events. Human carriers of the ApoA-1 Milano variant have a reduced incidence of CV disease. Regression of atherosclerotic plaque burden was previously observed on intravascular ultrasound (IVUS) with ETC-216, a predecessor of MDCO-216. MDCO-216, a complex of dimeric ApoA-1 Milano and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, is being developed to reduce atherosclerotic plaque burden and CV events. We investigated the efficacy and safety of a single infusion of MDCO-216 in healthy volunteers and in patients with coronary artery disease (CAD). Methods and results Twenty-four healthy volunteers and 24 patients with documented CAD received a 2-h infusion of MDCO-216 in a randomized, placebo controlled, single ascending dose study. Five cohorts of healthy volunteers and four cohorts of CAD patients received ApoA-1 Milano doses ranging from 5 to 40 mg/kg. Subjects were followed for 30 days. Dose-dependent increases in ApoA-1, phospholipid, and pre-beta 1 HDL and decreases in ApoE were observed. Prominent and sustained increases in triglyceride, and decreases in HDL-C, endogenous ApoA-1 and ApoA-II occurred at doses >20 mg/kg and profound increases in ABCA1-mediated cholesterol efflux were observed. Other lipid and lipoprotein parameters were generally unchanged. MDCO-216 was well tolerated. Conclusions MDCO-216-modulated lipid parameters profoundly increased ABCA1-mediated cholesterol efflux and was well tolerated. These single-dose data support further development of this agent for reducing atherosclerotic disease and subsequent CV events. PMID:27418968

  12. Hepatic Arterial Infusion Chemotherapy through a Port-Catheter System as Preoperative Initial Therapy in Patients with Advanced Liver Dysfunction due to Synchronous and Unresectable Liver Metastases from Colorectal Cancer

    SciTech Connect

    Iguchi, Toshihiro; Arai, Yasuaki; Inaba, Yoshitaka Yamaura, Hidekazu; Sato, Yozo; Miyazaki, Masaya; Shimamoto, Hiroshi

    2008-01-15

    Purpose. We retrospectively evaluated the safety and efficacy of preoperative initial hepatic arterial infusion chemotherapy (HAIC) through a port-catheter system in patients with liver dysfunction due to synchronous and unresectable liver metastases. The aim of HAIC was to improve patients' clinical condition for later surgical removal of primary colorectal cancer. Methods. Port-catheter systems were placed radiologically in 21 patients (mean age 58.6 {+-} 8.1 years) with liver dysfunction due to synchronous liver metastases from colorectal cancer. Initial HAIC of 1,000 mg/m{sup 2} 5-fluorouracil was administered weekly as a 5 hr continuous infusion through this system. Surgical removal of the primary lesion was planned after HAIC improved the liver function. Results. Port-catheter system placement was successful in all patients without severe complications. Patients were followed up for a median of 309 days (range 51-998 days). After starting HAIC, no severe adverse events that caused drug loss and treatment postponement or suspension were observed in any of the patients. HAIC was performed a mean of 4.5 {+-} 3.0 times and the liver function improved in all patients. Curative (n = 18) or palliative (n = 1) surgical removal of the primary lesion was performed. The remaining 2 patients died because extrahepatic metastases developed and their performance status worsened; thus, surgery could not be performed. The median survival times of all patients and the operated patients were 309 and 386 days, respectively. Conclusion. Initial HAIC administration is a safe and efficacious method for improving liver function prior to operative resection of primary colorectal cancer in patients with liver dysfunction due to synchronous and unresectable liver metastases.

  13. Urokinase does not prevent abdominal adhesion formation in rats.

    PubMed

    Rivkind, A I; Lieberman, N; Durst, A L

    1985-01-01

    Damage to the fibrinolytic system preventing the resolution of temporary fibrinous adhesions was repeatedly mentioned as an etiological factor in the process of adhesion formation. We experimentally induced abdominal adhesions in rats by gentle scraping of the entire small bowel. Severe adhesions, sometimes accompanied by intestinal obstruction, developed in all of the control animals. Urokinase, a commonly used and potent fibrinolytic agent and a known plasminogen activator, was administered intragastrically, intraperitoneally, or intravenously at various doses ranging from 5,000 to 100,000 U/kg. Urokinase had no effect on the prevention of abdominal adhesions, nor did it reduce the severity or frequency of adhesion formation. PMID:4043158

  14. Fluorescent-Antibody Measurement Of Cancer-Cell Urokinase

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.

    1993-01-01

    Combination of laboratory techniques provides measurements of amounts of urokinase in and between normal and cancer cells. Includes use of fluorescent antibodies specific against different forms of urokinase-type plasminogen activator, (uPA), fluorescence microscopy, quantitative analysis of images of sections of tumor tissue, and flow cytometry of different uPA's and deoxyribonucleic acid (DNA) found in suspended-tumor-cell preparations. Measurements provide statistical method for indicating or predicting metastatic potentials of some invasive tumors. Assessments of metastatic potentials based on such measurements used in determining appropriate follow-up procedures after surgical removal of tumors.

  15. Rapid and early α-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma

    PubMed Central

    OYAMA, KENJI; KODA, MASAHIKO; SUGIHARA, TAKAAKI; KISHINA, MANABU; MIYOSHI, KENICHI; OKAMOTO, TOSHIAKI; HODOTSUKA, MASANORI; FUJISE, YUKI; MATONO, TOMOMITSU; TOKUNAGA, SHIHO; OKAMOTO, KINYA; HOSHO, KEIKO; OKANO, JUNICHI; MURAWAKI, YOSHIKAZU

    2015-01-01

    The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects. PMID:26137283

  16. Urokinase production by electrophoretically separated cultured human embryonic kidney cells

    NASA Technical Reports Server (NTRS)

    Kunze, M. E.; Plank, L. D.; Giranda, V.; Sedor, K.; Todd, P. W.

    1985-01-01

    Urokinase is a plasminogen activator found in urine. Relatively pure preparations have been tested in Europe, Japan and the United States for the treatment of deep vein thrombosis and other dangerous blood clots. Human embryonic kidney cell cultures have been found to produce urokinase at much higher concentrations, but less than 5% of the cells in typical cultures are producers. Since human diploid cells become senescent in culture the selection of clones derived from single cells will not provide enough material to be useful, so a bulk purification method is needed for the isolation of urokinase producing cell populations. Preparative cell electrophoresis was chosen as the method, since evidence exists that human embryonic cell cultures are richly heterogeneous with respect to electrophoretic mobility, and preliminary electrophoretic separations on the Apollo-Soyuz space flight produced cell populations that were rich in urokinase production. Similarly, erythropoietin is useful in the treatment of certain anemias and is a kidney cell duct, and electrophoretically enriched cell populations producing this product have been reported. Thus, there is a clear need for diploid human cells that produce these products, and there is evidence that such cells should be separable by free-flow cell electrophoresis.

  17. A Case Report of Long-Term Survival following Hepatic Arterial Infusion of L-Folinic Acid Modulated 5-Fluorouracil Combined with Intravenous Irinotecan and Cetuximab Followed by Hepatectomy in a Patient with Initially Unresectable Colorectal Liver Metastases

    PubMed Central

    Van Bael, Kobe; Jansen, Yanina; Seremet, Teofila; Engels, Benedikt; Delvaux, Georges

    2015-01-01

    A 43-year-old women admitted to our hospital for weight loss, anorexia, and abdominal pain was diagnosed with sigmoid neoplasm and multiple bilobar liver metastases. This patient received six cycles of systemic FOLFOX prior to a laparoscopically assisted anterior resection of the rectosigmoid for a poorly differentiated invasive adenocarcinoma T2N2M1, K-RAS negative (wild type). Hepatic arterial infusion (HAI) of L-folinic acid modulated 5-fluorouracil (LV/5-FU) with intravenous (iv) irinotecan (FOLFIRI) and cetuximab as adjuvant therapy resulted in a complete metabolic response (CR) with CEA normalization. A right hepatectomy extended to segment IV was performed resulting in (FDG-)PET negative remission for 7 months. Solitary intrahepatic recurrence was effectively managed by local radiofrequent ablation following 6c FOLFIRI plus cetuximab iv. Multiple lung lesions and recurrence of pulmonary and local lymph node metastases were successfully treated with fractionated stereotactic radiotherapy (50 Gy) and iv LV/5-FU/oxaliplatin (FOLFOX) plus cetuximab finally switched to panitumumab with CR as a result. At present the patient is in persistent complete remission of her stage IV colorectal cancer, more than 5 years after initial diagnosis of the advanced disease. Multidisciplinary treatment with HAI of chemotherapy (LV/5-FU + CPT-11) plus EGFR-inhibitor can achieve CR of complex unresectable LM and can even result in hepatectomy with possible long-term survival. PMID:26064730

  18. Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

    PubMed Central

    Gibson, P; Birchall, I; Rosella, O; Albert, V; Finch, C; Barkla, D; Young, G

    1998-01-01

    Background—The functions of urokinase in intestinal epithelia are unknown. 
Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. 
Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. 
Results—From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height. 
Conclusions—Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine. 

 Keywords: urokinase; intestinal epithelium; colon; epithelial proliferation PMID:9824347

  19. Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, Osama Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo

    2007-09-15

    Purpose. The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. Materials and Methods. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). Results. On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median {+-} SD, 16.0 {+-} 3.7 vs. 8.0 {+-} 1.4 months; p < 0.05). Conclusions. We conclude that in patients with advanced

  20. Infusion-related air embolism.

    PubMed

    Cook, Lynda S

    2013-01-01

    Vascular air embolism as a medically induced complication may be associated with numerous treatments and therapies. In infusion therapy, the risk is associated with venous and arterial catheterization as well as various other invasive procedures and much of the equipment used for them. The manner of air entry and the presentation of symptoms may vary greatly. Appropriate treatment options are dependent on air entry routes. Nurses need to be aware of the common and seldom-considered causes of air embolism to be able to guard against this complication, yet adequately support the patient if it occurs.

  1. Method of infusion extraction

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R. (Inventor)

    1989-01-01

    Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

  2. Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes

    PubMed Central

    Alfano, Massimo; Cinque, Paola; Giusti, Guido; Proietti, Silvia; Nebuloni, Manuela; Danese, Silvio; D’Alessio, Silvia; Genua, Marco; Portale, Federica; Lo Porto, Manuela; Singhal, Pravin C.; Rastaldi, Maria Pia; Saleem, Moin A.; Mavilio, Domenico; Mikulak, Joanna

    2015-01-01

    Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms’ tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur−/− mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR. PMID:26380915

  3. Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes.

    PubMed

    Alfano, Massimo; Cinque, Paola; Giusti, Guido; Proietti, Silvia; Nebuloni, Manuela; Danese, Silvio; D'Alessio, Silvia; Genua, Marco; Portale, Federica; Lo Porto, Manuela; Singhal, Pravin C; Rastaldi, Maria Pia; Saleem, Moin A; Mavilio, Domenico; Mikulak, Joanna

    2015-09-18

    Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms' tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur(-/-) mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR.

  4. Linkage of extracellular plasminogen activator to the fibroblast cytoskeleton: colocalization of cell surface urokinase with vinculin

    PubMed Central

    1988-01-01

    Several cell types display binding sites for [125I]urokinase (Vassalli, J.-D., D. Baccino, D. Belin. 1985. J. Cell Biol. 100:86-92) which in certain cases are occupied with endogenous urokinase. These sites appear to focus urokinase at cell surfaces and hence may participate in tissue matrix destruction and cell invasion. Recently Pollanen et al. (1987) demonstrated that the cell surface urokinase of human fibroblasts and fibrosarcoma cells is deposited underneath the cells in strands, apparently at sites of cell-to-substratum contact. Here, using immunofluorescence double labeling, we show that the urokinase strands present on human foreskin fibroblasts are colocalized with strands of vinculin, an intracellular actin-binding protein that is deposited at cell-to-substratum focal adhesion sites. Thus, this indicates linkage of the plasminogen/plasmin system both to sites of cell adhesion and to the cytoskeleton. The urokinase strands on HT 1080 fibrosarcoma cells are more numerous and have shapes that are more tortuous than those on normal fibroblasts. In intact HT 1080 cells, colocalized vinculin strands are obscured by an intense background of soluble vinculin but are apparent on isolated ventral plasma membranes. Certain properties of the urokinase strands suggest that they are related to the [125I]urokinase-binding sites that have been described by several groups: (a) incubating fibroblasts with dexamethasone for 48 h or at pH 3 at 5 degrees C for 10 min greatly decreases the number and intensity of the urokinase strands; (b) strands reappear when glucocorticoid- treated cells are incubated with exogenous 54-kD (but not 35-kD) urokinase, and this process is inhibited by a previously described 16- amino acid peptide that blocks [125I]urokinase binding to the cells. PMID:3129438

  5. Initial Results of Catheter-Directed Ultrasound-Accelerated Thrombolysis for Thromboembolic Obstructions of the Aortofemoral Arteries: A Feasibility Study

    SciTech Connect

    Schrijver, A. Marjolein; Reijnen, Michel M. P. J.; Oostayen, Jacques A. van; Hoksbergen, Arjan W. J.; Lely, Rutger J.; Leersum, Marc van; Vries, Jean-Paul P. M. de

    2012-04-15

    Purpose: This article reports the 30-day technical and clinical outcome of ultrasound (US)-accelerated thrombolysis in patients with aortofemoral arterial thromboembolic obstructions. Methods: A prospective cohort study was conducted from December 2008 to December 2009 of patients who were treated with US-accelerated thrombolysis for thromboembolic obstructions of aortofemoral arteries or bypasses. Urokinase was infused in a dosage of 100,000 IU per hour. Twice daily, a control angiography was performed. Thirty-day follow-up consisted of duplex scanning, combined with magnetic resonance angiography. Results: The study included 21 consecutive patients (20 men; median age, 66 (range, 52-80) years) with 24% artery versus 76% bypass occlusions. Median duration of symptoms was 11 (range, 7-140) days. Median occlusion length was 32 (range, 6-80) cm. In 20 patients (95%), an US-accelerated thrombolysis catheter could be successfully placed. In one patient, placement of an US-accelerated thrombolysis catheter was technically not feasible, and therefore a standard catheter was placed. Median thrombolysis time was 26.5 (range, 8.5-72) hours. Complete thrombolysis (>95% lysis of thrombus) was achieved in 20 patients; in 9 patients within 24 hours. Median ankle-brachial index (ABI) increased from 0.28 (range, 0-0.85) to 0.91 (range, 0.58-1.35). One patient had a thromboembolic complication and needed surgical intervention. No hemorrhagic complications, and no deaths occurred. At 30-day follow-up, 17 of 21 patients (81%) had a patent artery or bypass. Conclusions: This feasibility study showed a high technical success rate of US-accelerated thrombolysis for aortofemoral arterial obstructions. US-accelerated thrombolysis led to complete lysis within 24 hours in almost half of patients, with a low 30-day major complication rate.

  6. Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up

    PubMed Central

    Guan, Yong-song; Liu, Yuan; Zou, Qing; He, Qing; La, Zi; Yang, Lin; Hu, Ying

    2009-01-01

    Objective: In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) injection in patients with advanced non-small-cell lung cancer (NSCLC) in the combination with the therapy of bronchial arterial infusion (BAI). Methods: A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 (the combo group), while the remaining 39 were treated with only BAI (the control group). Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer Institute’s Common Toxicity Criteria and response evaluation criteria in solid tumor (RECIST), respectively. Time to progression (TTP) and survival rates were also analyzed by Kaplan-Meier method. Results: In the combo group, 19 patients received a total of 49 injections of rAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia (P<0.05) but more arthralgia, fever, influenza-like symptom, and myalgia (P<0.05), compared with the control group. The overall response rates (complete response (CR)+partial response (PR)) were 47.3% and 38.4% for the combo group and the control group, respectively (P>0.05). Patients in the combo group had a longer TTP than those in the control group (a median 7.75 vs 5.5 months, P=0.018). However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, compared with 92.31%, 69.23%, and 38.83% in the control group (P=0.224). Conclusion: Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the quality of life and delayed

  7. Successful Intra-Arterial Thrombolysis for Acute Ischemic Stroke in the Immediate Postpartum Period: Case Report

    SciTech Connect

    Mendez, Jose C. Masjuan, J.; Garcia, N.; Lecinana, M. de

    2008-01-15

    Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period.

  8. A Series of Cerebral Venous Sinus Thromboses Treated with Intra-Arterial tPA infused over Ten Hours with a 0.027-inch Catheter and Literature Review

    PubMed Central

    Ziu, Endrit; Haley, O'Hara; Ibrahimi, Muhammad; Simon, Scott

    2016-01-01

    Cerebral venous sinus thrombosis (CVST) can have devastating results, with mortality reported in 44% of cases. No randomized trials exist in order to define what qualifies as failure of conservative therapy, and there is no specific intervention to date which is considered safe and effective. Case series suggest that thrombolysis infusion is safer than thrombectomy, but methods of administration, dose, and duration of therapy tend to vary widely. We present three consecutive CVST patients treated with heparin who suffered both clinical and radiographic deterioration, and went on to have endovascular therapy. Each patient was successfully recanalized by placing a 0.027-inch microcatheter at the proximal portion of the thrombus and infusing 20 mg of alteplase dissolved in 1 liter of normal saline infused at 100 ml per hour for an infusion of 2 mg of alteplase per hour for ten hours.  PMID:27462480

  9. Intra-arterial chemotherapy for bilateral retinoblastoma via left ophthalmic artery and right anterior deep temporal artery

    PubMed Central

    Amans, Matthew R; Narvid, Jared; Halbach, Van V

    2014-01-01

    A 12-month-old boy with a history of bilateral retinoblastoma refractory to systemic chemotherapy, laser therapy and cryotherapy, with excellent response to previous intra-arterial melphalan infusion, presents with active tumour deposits in the right eye. Repeat intra-arterial chemotherapy was recommended. Previous bilateral melphalan infusion was uneventful using flow-guided catheterisation technique. Direct catheterisation of the right ophthalmic artery was unsuccessful despite employment of several flow-guided and over-the-wire catheters. Superselective catheterisation of the ipsilateral middle meningeal artery was unable to identify an anastomotic connection to the ophthalmic artery; however, angiography of the anterior deep temporal artery identified an alternate route for chemotherapy infusion. The anterior deep temporal artery was successfully and safely catheterised to infuse chemotherapy into the ophthalmic artery. The anterior deep temporal artery is an important potential anastomotic connection to the ophthalmic artery that can be used safely and effectively for central retinal artery chemotherapy infusion for retinoblastoma treatment. PMID:25240013

  10. Programmable physiological infusion

    NASA Technical Reports Server (NTRS)

    Howard, W. H.; Young, D. R.; Adachi, R. R. (Inventor)

    1974-01-01

    A programmable physiological infusion device and method are provided wherein a program source, such as a paper tape, is used to actuate an infusion pump in accordance with a desired program. The system is particularly applicable for dispensing calcium in a variety of waveforms.

  11. Finger necrosis after accidental radial artery puncture

    PubMed Central

    Kang, Jun Sik; Lee, Tae Rim; Cha, Won Chul; Shin, Tae Gun; Sim, Min Seob; Jo, Ik Joon; Song, Keun Jeong; Rhee, Joong Eui; Jeong, Yeon Kwon

    2014-01-01

    Radial artery puncture, an invasive procedure, is frequently used for critical patients. Although considered safe, severe complications such as finger necrosis can occur. Herein, we review the clinical course of finger necrosis after accidental radial artery puncture. A 63-year-old woman visited the emergency department (ED) with left second and third finger pain after undergoing intravenous (IV) access in her wrist for procedural sedation. During the IV access, she experienced wrist pain, which increased during the 12 hours prior to her ED presentation. Emergency angiography revealed a pseudoaneurysm in her left radial artery and absence of blood flow to the proper palmar digital artery. Subsequent angiointervention and urokinase thrombolysis failed. The second finger was eventually amputated owing to gangrene. Radial artery puncture can occur accidentally during IV wrist access, resulting in severe morbidity. Providers should carefully examine the puncture site and collateral flow, followed by multiple examinations to ensure distal circulation.

  12. Saline infusion sonohysterography.

    PubMed

    2004-01-01

    Saline infusion sonohysterography consists of ultrasonographic imaging of the uterus and uterocervical cavity, using real-time ultrasonography during injection of sterile saline into the uterus. When properly performed, saline infusion sonohysterography can provide information about the uterus and endometrium. The most common indication for sonohysterography is abnormal uterine bleeding. sonohysterography should not be performed in a woman who is pregnant or could be pregnant or in a woman with a pelvic infection or unexplained pelvic tenderness. Physicians who perform or supervise diagnostic saline infusion sonohysterograpy should have training, experience, and demonstrated competence in gynecologic ultrasonography and saline infusion sonohysterography. Portions of this document were developed jointly with the American College of Radiology and the American Institute of Ultrasound in Medicine. PMID:14968760

  13. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Performance testing carried out in the development of the prototype zero-g fluid infusion system is described and summarized. Engineering tests were performed in the course of development, both on the original breadboard device and on the prototype system. This testing was aimed at establishing baseline system performance parameters and facilitating improvements. Acceptance testing was then performed on the prototype system to verify functional performance. Acceptance testing included a demonstration of the fluid infusion system on a laboratory animal.

  14. Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets.

    PubMed

    Leifert, J A; Bossaller, L; Uhl, M

    2008-11-01

    Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms.

  15. The role of placental urokinase inhibitor in toxemia of pregnancy.

    PubMed

    Terao, T; Kobayashi, T

    1983-01-01

    The fibrinolysis of the uterus can be reversed during the course of pregnancy. The chief cause of this physiologic change is an increase of urokinase (UK) inhibitor in the placenta. The UK inhibitor also has a pathologic aspect that can influence the course of pregnancy. We have proven that the hypofibrinolysis of toxemic pregnant urine results from increased UK inhibitor. Furthermore, we have shown the existence of UK inhibitor in toxemic pregnant serum and the glomerulus. On the basis of these facts we propose that UK inhibitor leaks into the maternal blood stream from the placenta and inhibits the fibrinolytic activity of UK, forming microthrombuses in the glomerulus. Excess UK inhibitor in the placenta also suppresses the fibrinolytic activity of placental plasminogen activator (PPA). Thus microthrombuses are apt to be formed in both the placenta and glomerulus. Such pathologic inhibition of fibrinolysis strongly influences the course of toxemia. PMID:6360225

  16. Continuous quality improvement: improving hemodialysis catheter patency using urokinase.

    PubMed

    Northsea, C

    1996-12-01

    Opportunities for improvements in patient outcomes through applied continuous quality improvement (CQI) programs are endless and exciting. Improving vascular access outcomes has been a long-standing clinical problem for hemodialysis patients and the nephrology team. During the past few years there has been a dramatic increase in the use of dialysis catheters as permanent accesses for hemodialysis patients. All hemodialysis with dialysis catheters are at risk for catheter occlusion. An innovative, 2-year CQI program was developed, implemented, and designed to improve dialysis catheter patency rates with the use of urokinase. The CQI program resulted in a number of clinical outcomes that were beneficial to the patients and dialysis staff, and were cost-effective to the program.

  17. Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression.

    PubMed Central

    Rao, N K; Shi, G P; Chapman, H A

    1995-01-01

    Binding of urokinase to the glycolipid-anchored urokinase receptor (uPAR) has been implicated in macrophage differentiation. However, no biochemical markers of differentiation have yet been directly linked to uPAR occupancy. As extensive changes in proteolytic profile characterize monocytic differentiation, we have examined the role of uPAR occupancy on protease expression by differentiating phagocytes. Antibodies to either urokinase or to uPAR that prevent receptor binding inhibited induction of cathepsin B in cultured monocytes and both cathepsin B and 92-kD gelatinase mRNA and protein in phorbol diester-stimulated myeloid cells. Mannosamine, an inhibitor of glycolipid anchor assembly, also blocked protease expression. Anti-catalytic urokinase antibodies, excess inactive urokinase, or aprotinin had no effect, indicating that receptor occupancy per se regulated protease expression. Antibodies to the integrins CD11a and CD29 or to the glycolipid-anchored proteins CD14 and CD55 also had no effect. Protease induction was independent of matrix attachment. Antibodies to urokinase or uPAR affected neither the decrease in cathepsin G nor the increase in tumor necrosis factor-alpha in phorbol ester-stimulated cells. These data establish that uPAR is a multifunctional receptor, not only promoting pericellular proteolysis and matrix attachment, but also effecting cysteine- and metallo-protease expression during macrophage differentiation. Images PMID:7615819

  18. Saline resuscitation after fixed-volume hemorrhage. Role of resuscitation volume and rate of infusion.

    PubMed Central

    Lilly, M P; Gala, G J; Carlson, D E; Sutherland, B E; Gann, D S

    1992-01-01

    The authors have reported previously that small-volume resuscitation (1.8 x bled volume) with 0.9% NaCl restores blood volume and attenuates hormonal responses after large hemorrhage without correction of arterial hypotension. The authors studied the role of rate of infusion in this observation in chronically prepared dogs (aortic flow probe, right atrial pressure and volume, and arterial catheters) after 30% hemorrhage (24.1 +/- 0.4 mL/kg). After 30 minutes, subjects were observed either without treatment (no resuscitation) or with infusion of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols: (1) impulse infusion over 10 minutes, (2) variable rate infusion, bolus with tapering infusion, or (3) constant rate infusion. Significant improvement in cardiac output and in blood volume and significant decreases of vasopressin and arterial catecholamines were observed in all fluid-treated groups. This benefit was relatively independent of rate of infusion, although impulse infusion produced greater early improvement, which dissipated with time, and constant rate infusion produced better late results. In none of the fluid-treated groups were these improvements reflected in improved mean arterial pressure compared with the no resuscitation group. The authors conclude that small-volume, slow-rate saline infusion produces physiologic benefits that cannot be assessed by easily measured clinical parameters. Thus, early resuscitation after trauma could aid patients even if arterial pressure is unchanged. This benefit might be even greater in patients with uncontrolled bleeding because arterial pressure, and hence bleeding, may not be increased by resuscitation of this type. A reassessment of the value of prehospital fluid resuscitation in the injured patient is warranted. PMID:1503518

  19. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    Hammond, J. C.

    1975-01-01

    Development of a fluid infusion system was undertaken in response to a need for an intravenous infusion device operable under conditions of zero-g. The initial design approach, pursued in the construction of the first breadboard instrument, was to regulate the pressure of the motive gas to produce a similar regulated pressure in the infusion liquid. This scheme was not workable because of the varying bag contact area, and a major design iteration was made. A floating sensor plate in the center of the bag pressure plate was made to operate a pressure regulator built into the bellows assembly, effectively making liquid pressure the directly controlled variable. Other design changes were made as experience was gained with the breadboard. Extensive performance tests were conducted on both the breadboard and the prototype device; accurately regulated flows from 6 m1/min to 100 m1/min were achieved. All system functions were shown to operate satisfactorily.

  20. [Transposition of Great Artery].

    PubMed

    Konuma, Takeshi; Shimpo, Hideto

    2015-07-01

    Transposition of the great artery is one of common congenital cardiac disease resulting cyanosis. Death occurs easily in untreated patients with transposition and intact ventricular septal defect (VSD) in infancy at a few days of age when posterior descending coronary artery (PDA) closed. Since there are 2 parallel circulations, flow from pulmonary to systemic circulation is necessary for systemic oxygenation, and Balloon atrial septostomy or prostaglandin infusion should be performed especially if patient do not have VSD. Although the advent of fetal echocardiography, it is difficult to diagnose the transposition of the great arteries (TGA) as abnormality of great vessels is relatively undistinguishable. The diagnosis of transposition is in itself an indication for surgery, and arterial switch procedure is performed in the case the left ventricle pressure remains more than 2/3 of systemic pressure. Preoperative diagnosis is important as associated anomalies and coronary artery branching patterns are important to decide the operative indication and timing of surgery.

  1. Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

    PubMed Central

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan; Wei, Hao; Liu, Shihui; Lund, Ida K.; Høyer-Hansen, Gunilla; Dichek, David A.

    2015-01-01

    Aims Elevated activity of urokinase plasminogen activator (uPA) and MMPs in human arteries is associated with accelerated atherosclerosis, aneurysms, and plaque rupture. We used Apoe-null mice with macrophage-specific uPA overexpression (SR-uPA mice; a well-characterized model of protease-accelerated atherosclerosis) to investigate whether systemic inhibition of proteolytic activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis and aortic dilation. Methods and results SR-uPA mice were fed a high-fat diet for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1) or a control antibody. mU1-treated mice were also compared with PBS-treated non-uPA-overexpressing Apoe-null mice. Other SR-uPA mice were treated with one of three doses of a limited-spectrum synthetic MMP inhibitor (XL784) or vehicle. mU1 reduced aortic root intimal lesion area (20%; P = 0.05) and aortic root circumference (12%; P = 0.01). All XL784 doses reduced aortic root intimal lesion area (22–29%) and oil-red-O-positive lesion area (36–42%; P < 0.05 for all doses and both end points), with trends towards reduced aortic root circumference (6–10%). Neither mU1 nor XL784 significantly altered percent aortic surface lesion coverage. Several lines of evidence identified MMP-13 as a mediator of uPA-induced aortic MMP activity. Conclusions Pharmacological inhibition of either uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition decreased aortic dilation. Differential effects of both agents on aortic root vs. distal aortic atherosclerosis suggest prevention of atherosclerosis progression vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for treating atherosclerosis. PMID:25616415

  2. The Urine Urokinase Concentration in End Stage Renal Disease with Acquired Renal Cyst

    PubMed Central

    Hong, Sae Yong; Yang, Dong Ho; Lee, Byoung Ho; Ki, Eun Kyong; Chung, Kwang Hoe

    1991-01-01

    To see whether there was any difference in the urine urokinase concentration between acquired cystic kidney disease (ACKD) group and control (non cyst) group in end stage renal disease patients (ESRD), we evaluated fifty ESRD patients who had been maintained on chronic hemodialysis for various period. The urine urokinase concentration was higher in the ACKD group (17.5±14.7 unit/ml, range 13.5–47.0 unit/ml, n=9) than the control group (4.1±3.4 unit/ml, range 0.5–12.0 unit/ml, n=36) (p<0.001), and polycyst group (2.6±1.8 unit/ml, range 1.0–5.1 unit/ml, n=5) (p<0.01). But there was no difference between the control group and polycyst group. In the control group and the ACKD group, there was a direct relation between the dialysis duration and the urokinase concentration and the longer the dialysis duration, the higher the urine urokinase concentration (r squared=0.424, p=0.0001). The hemodialysis duration was longer in the ACKD group (42±17.0 months) than the control group (20.0±12.5 months) (p<0.005). These findings suggest that urokinase may be responsible for cystogenic degeneration in ESRD. PMID:1807367

  3. Application of Molecular Modeling to Urokinase Inhibitors Development

    PubMed Central

    Sulimov, V. B.; Katkova, E. V.; Oferkin, I. V.; Sulimov, A. V.; Romanov, A. N.; Roschin, A. I.; Beloglazova, I. B.; Plekhanova, O. S.; Tkachuk, V. A.; Sadovnichiy, V. A.

    2014-01-01

    Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program), postprocessing (DISCORE program), direct generalized docking (FLM program), and the application of the quantum chemical calculations (MOPAC package), search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM. PMID:24967388

  4. Dissecting aneurysm of the middle cerebral artery treated with heparin infusion in a 6-year-old child; neurological recovery with delayed spontaneous thrombosis: case illustration and literature review.

    PubMed

    Anichini, G; Passacantilli, E; Lenzi, J; Guidetti, G; Santoro, A

    2012-04-01

    Aneurysms in the pediatric population are a rare pathology with specific features which requires a deep knowledge of their pathogenesis for the best therapeutic choice; the authors report their experience with a patient presenting aneurysm of the middle cerebral artery (MCA) associated with proximal stenosis of the vessel. A six-year-old girl came to our observation after sudden onset of headache and left hemiparesis. Angio-MRI and angio-CT scan showed a right MCA dissecting aneurysms associated with proximal stenosis of the vessel. Patient started a therapy with low molecular weight heparin (LMWH), replaced, 15 days later, with acetyl-salicylic acid (ASA). Patient showed a rapid and almost complete neurological recovery, despite several radiological exams confirmed a complete occlusion of the right MCA. As many other authors noted, dissecting aneurysms in the pediatric population are probably due to a defect of the entire arterial wall. Combination of stenosis, turbulence and partial thrombosis of the aneurysm led to a complete occlusion of artery involved, leading to the formation of collateral circles. In our case, complete thrombosis was probably delayed with anticoagulant therapy and the progressive reinforcement of collateral circles lead to the patient's neurological recovery.

  5. Feeding Artery of Laryngeal and Hypopharyngeal Cancers: Role of the Superior Thyroid Artery in Superselective Intraarterial Chemotherapy

    SciTech Connect

    Terayama, Noboru Sanada, Junichiro; Matsui, Osamu; Kobayashi, Satoshi; Kawashima, Hiroko; Yamashiro, Masashi; Takanaka, Tsuyoshi; Kumano, Tomoyasu; Yoshizaki, Tomokazu; Furukawa, Mitsuru

    2006-08-15

    The purpose of this study was to elucidate the role of the superior thyroid artery in intra-arterial infusion chemotherapy for laryngeal and hypopharyngeal cancers. Thirty-nine patients with laryngeal cancer and 29 patients with hypopharyngeal cancer underwent intra-arterial infusion chemotherapy. We performed a retrospective analysis of the feeding arteries confirmed by computed tomography during selective arteriography and compared the results with the extent of the tumors. In 14 of 39 laryngeal and 15 of 29 hypopharyngeal cancers, the tumor did not cross the midline (group 1). In the remaining 25 and 14 cancers, respectively, the tumor crossed the midline or located in the center (group 2). For 13 of 14 laryngeal and 7 of 15 hypopharyngeal cancers in group 1 and for 6 of 25 laryngeal cancers in group 2, the entire tumor was contrast enhanced by the ipsilateral superior thyroid and/or superior laryngeal artery. For 12 of 25 laryngeal and 1 of 14 hypopharyngeal cancers in group 2, the entire tumor was contrast enhanced by the bilateral superior thyroid artery. For the other patients, infusion via the other arterial branches such as the inferior thyroid and the lingual arteries were needed to achieve contrast enhancement of the entire tumor. Superselective intra-arterial chemotherapy for laryngeal cancer from the superior thyroid artery is appropriate, whereas that for hypopharyngeal cancer is less sufficient. To accomplish contrast enhancement of the entire tumor, additional intra-arterial infusion from other arteries such as the inferior thyroid artery is often necessary.

  6. Imaging Active Urokinase Plasminogen Activator in Prostate Cancer

    PubMed Central

    LeBeau, Aaron M.; Sevillano, Natalia; Markham, Kate; Winter, Michael B.; Murphy, Stephanie T.; Hostetter, Daniel R.; West, James; Lowman, Henry; Craik, Charles S.; VanBrocklin, Henry F.

    2015-01-01

    The increased proteolytic activity of membrane-bound and secreted proteases on the surface of cancer cells and in the transformed stroma is a common characteristic of aggressive metastatic prostate cancer. We describe here the development of an active site-specific probe for detecting a secreted peritumoral protease expressed by cancer cells and the surrounding tumor microenvironment. Using a human fragment antigen binding phage display library, we identified a human antibody termed U33 that selectively inhibited the active form of the protease urokinase plasminogen activator (uPA, PLAU). In the full-length immunoglobulin form, U33 IgG labeled with near-infrared fluorophores or radionuclides allowed us to non-invasively detect active uPA in prostate cancer xenograft models using optical and single-photon emission computed tomography (SPECT) imaging modalities. U33 IgG labeled with 111In had a remarkable tumor uptake of 43.2% injected dose per gram (%ID/g) 72hr post tail vein injection of the radiolabeled probe in subcutaneous xenografts. Additionally, U33 was able to image active uPA in small soft-tissue and osseous metastatic lesions using a cardiac dissemination prostate cancer model that recapitulated metastatic human cancer. The favorable imaging properties were the direct result of U33 IgG internalization through an uPA receptor mediated mechanism where U33 mimicked the function of the endogenous inhibitor of uPA to gain entry into the cancer cell. Overall, our imaging probe targets a prostate cancer-associated protease, through a unique mechanism, allowing for the non-invasive preclinical imaging of prostate cancer lesions. PMID:25672980

  7. Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency

    PubMed Central

    Chen, Zaixing; Zhao, Runzhen; Zhao, Meimi; Liang, Xinrong; Bhattarai, Deepa; Dhiman, Rohan; Shetty, Sreerama; Idell, Steven

    2014-01-01

    Epithelial sodium channels (ENaC) govern transepithelial salt and fluid homeostasis. ENaC contributes to polarization, apoptosis, epithelial-mesenchymal transformation, etc. Fibrinolytic proteases play a crucial role in virtually all of these processes and are elaborated by the airway epithelium. We hypothesized that urokinase-like plasminogen activator (uPA) regulates ENaC function in airway epithelial cells and tested that possibility in primary murine tracheal epithelial cells (MTE). Both basal and cAMP-activated Na+ flow through ENaC were significantly reduced in monolayers of uPA-deficient cells. The reduction in ENaC activity was further confirmed in basolateral membrane-permeabilized cells. A decrease in the Na+-K+-ATPase activity in the basolateral membrane could contribute to the attenuation of ENaC function in intact monolayer cells. Dysfunctional fluid resolution was seen in uPA-disrupted cells. Administration of uPA and plasmin partially restores ENaC activity and fluid reabsorption by MTEs. ERK1/2, but not Akt, phosphorylation was observed in the cells and lungs of uPA-deficient mice. On the other hand, cleavage of γ ENaC is significantly depressed in the lungs of uPA knockout mice vs. those of wild-type controls. Expression of caspase 8, however, did not differ between wild-type and uPA−/− mice. In addition, uPA deficiency did not alter transepithelial resistance. Taken together, the mechanisms for the regulation of ENaC by uPA in MTEs include augmentation of Na+-K+-ATPase, proteolysis, and restriction of ERK1/2 phosphorylation. We demonstrate for the first time that ENaC may serve as a downstream signaling target by which uPA controls the biophysical profiles of airway fluid and epithelial function. PMID:25172911

  8. Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography

    PubMed Central

    Panigada, Mauro; Zacchetti, Lucia; L’Acqua, Camilla; Cressoni, Massimo; Anzoletti, Massimo Boscolo; Bader, Rossella; Protti, Alessandro; Consonni, Dario; D’Angelo, Armando; Gattinoni, Luciano

    2015-01-01

    Introduction Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. Methods This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. Results UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6–13) vs 5 (4–7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93–0.98, p = 0.003). Conclusions Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality. PMID:26308340

  9. Neuroprotection by urokinase plasminogen activator in the hippocampus.

    PubMed

    Cho, Eunsil; Lee, Kyung Jin; Seo, Jung-Woo; Byun, Catherine Jeonghae; Chung, Sun-Ju; Suh, Dae Chul; Carmeliet, Peter; Koh, Jae-Young; Kim, Jong S; Lee, Joo-Yong

    2012-04-01

    Tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which are both used for thrombolytic treatment of acute ischemic stroke, are serine proteases that convert plasminogen to active plasmin. Although recent experimental evidences have raised controversy about the neurotoxic versus neuroprotective roles of tPA in acute brain injury, uPA remains unexplored in this context. In this study, we evaluated the effect of uPA on neuronal death in the hippocampus of mice after kainate-induced seizures. In the normal brain, uPA was localized to both nuclei and cytosol of neurons. Following severe kainate-induced seizures, uPA completely disappeared in degenerating neurons, whereas uPA-expressing astrocytes substantially increased, suggesting reactive astrogliosis. uPA-knockout mice were more vulnerable to kainate-induced neuronal death than wild-type mice. Consistent with this, inhibition of uPA by intracerebral injection of the uPA inhibitor UK122 increased the level of neuronal death. In contrast, prior administration of recombinant uPA significantly attenuated neuronal death. Collectively, these results indicate that uPA renders neurons resistant to kainate-induced excitotoxicity. Moreover, recombinant uPA suppressed cell death in primary cultures of hippocampal neurons exposed to H2O2, zinc, or various excitotoxins, suggesting that uPA protects against neuronal injuries mediated by the glutamate receptor, or by oxidation- or zinc-induced death signaling pathways. Considering that tPA may facilitate neurodegeneration in acute brain injury, we suggest that uPA, as a neuroprotectant, might be beneficial for the treatment of acute brain injuries such as ischemic stroke.

  10. [Intraosseous infusion for adults].

    PubMed

    Leidel, B A; Kirchhoff, C

    2008-04-01

    Intraosseous (IO) infusion methods have been common for emergency treatment in infants and children for years. The role of IO access in adults is however much less clear, but its importance in this patient group is increasing, and different devices are available today. Each device has strengths and weaknesses, but all achieve rapid vascular access even in challenging situations. The potential of IO access regarding both therapeutic and diagnostic options has been shown in several operational studies in and out of hospital. Insertion times require between 1 and 2 min in most cases, while insertion and handling of the IO access devices seem to be easy and reliable. The flow rates of IO access devices for adults are lower than those of large-bore peripheral intravenous catheters, but fluid resuscitation is possible in most cases at least with pressure bag infusion systems. Most drugs administered intravenously can be given intraosseously in equivalent dosages and with the same effects. Nevertheless the limitations and risks of IO access routes need to be considered for each application. Rapid IO access is now possible in all age groups, and the 2005 AHA Guidelines favor it over drug administration via the endotracheal tube. PMID:18250995

  11. Increased migration of murine keratinocytes under hypoxia is mediated by induction of urokinase plasminogen activator.

    PubMed

    Daniel, Richard J; Groves, Richard W

    2002-12-01

    One of the key consequences of cutaneous wounding is the development of tissue hypoxia. Recent data have suggested that this is a potent stimulus for increased keratinocyte migration and hence re-epithelialization, although the mechanisms responsible for this remain unclear. In this study we have investigated the relationship between hypoxia, plasminogen activation, and in vitro wound healing. Exposure of keratinocyte cultures to hypoxia resulted in upregulation of urokinase plasminogen activator mRNA and a subsequent increase in urokinase plasminogen activator-mediated plasminogen activation, as determined by indirect chromogenic peptide assay and plasminogen-linked zymography. Analysis of keratinocyte wound healing in vitro confirmed enhanced wound closure in hypoxic cultures compared with normoxic cultures after 16 h. Pretreatment of normoxic and hypoxic cultures with mitomycin C and cytochalasin B indicated that in this system wound closure was due to keratinocyte migration rather than proliferation. Addition of the broad-spectrum serine proteinase inhibitor, p-aminobenzamidine, or the specific urokinase plasminogen activator inhibitors, amiloride and WX-293, significantly reduced wound closure in hypoxic cultures and abrogated the hypoxic enhancement of wound closure. These data indicate a central role for urokinase plasminogen activators in hypoxic keratinocyte migration and suggest a potential mechanism for enhanced re-epithelialization of wounds under low oxygen tensions. PMID:12485432

  12. Urokinase can reduce heparin dose in patients with hypercoagulable states during hemodialysis.

    PubMed

    Ren, Wanjun; Wei, Fang; Sha, Yabin; Wang, Qi; Xie, Lin

    2015-05-01

    Heparin is routinely administered at high doses during hemodialysis to patients with hypercoagulable states. This study aimed to evaluate the safety and efficacy of low-dose heparin in combination with urokinase in this patient population. The presence of a hypercoagulable state was confirmed by thromboelastography. Doses of heparin and urokinase were adjusted based on activated partial thromboplastin time (APTT). Clotting in the extracorporeal circuit was evaluated by a semi-quantitative index. Prothrombin time (PT) and APTT were measured before, during and after dialysis. Kt/V(urea) was used to assess the efficacy of dialysis. D-dimer levels were measured 2 h after the start of hemodialysis. Hemodialysis data with heparin administered alone prior to dialysis were used as control in the present study. With urokinase treatment, the initial dose of heparin was reduced by 45.0 ± 11.4% during hemodialysis and the maintenance dose by 46.8 ± 12.8% compared with heparin alone. No side effects due to urokinase were observed. Bleeding events were rare. Post-dialysis PT (12.99 ± 1.41 vs. 15.22 ± 3.12 s, p = 0.02) and APTT (97.75 ± 43.62 vs. 140.16 ± 30.12 s, p = 0.002) with urokinase plus heparin were significantly shorter than with heparin alone. Finally, during dialysis, D-dimer levels were significantly higher with heparin alone (0.21 ± 0.11 mg/L) than with heparin and urokinase (0.169 ± 0.122 mg/L, p = 0.017). In conclusion, urokinase significantly reduced the dose of heparin required during hemodialysis without any side effects in patients with hypercoagulable states during hemodialysis.

  13. Abnormal thallium 201 scintigraphy during low-dose vasopressin infusions

    SciTech Connect

    Davison, R.; Kaplan, K.; Bines, A.; Spies, S.; Reed, M.T.; Lesch, M.

    1986-12-01

    Thallium 201 (/sup 201/Tl) myocardial scans were obtained in 16 patients just prior to the discontinuation of a vasopressin infusion (.1 to .2 units/min) administered for the treatment of upper gastrointestinal bleeding. Repeat scintigraphy was performed two to three hours after the vasopressin was stopped. Eleven of the 16 patients (69 percent) demonstrated areas of decreased myocardial /sup 201/Tl uptake that resolved after the infusion was stopped. Heart rate-blood pressure product was significantly lower at the time of the second scan. Autopsies were secured in three of 11 scan-positive patients: one had severe coronary artery obstruction, one nonsignificant disease, and another had normal coronary arteries. Vasopressin, even at low doses, can induce abnormalities in myocardial perfusion that are probably mediated by a direct effect on the coronary circulation. They are usually not detectable by routine monitoring techniques and conceivably form the basis for the cardiovascular morbidity associated with the use of this agent.

  14. Tissue Blood Flow During Remifentanil Infusion With Carbon Dioxide Loading

    PubMed Central

    Kanbe, Hiroaki; Matsuura, Nobuyuki; Kasahara, Masataka; Ichinohe, Tatsuya

    2015-01-01

    The aim of this study was to investigate the effect of changes in end-tidal carbon dioxide tension (ETCO2) during remifentanil (Remi) infusion on oral tissue blood flow in rabbits. Eight male tracheotomized Japan White rabbits were anesthetized with sevoflurane under mechanical ventilation. The infusion rate of Remi was 0.4 μg/kg/min. Carbon dioxide was added to the inspired gas to change the inspired CO2 tension to prevent changes in the ventilating condition. Observed variables were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), common carotid artery blood flow (CCBF), tongue mucosal blood flow (TBF), mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF). The CCBF, TBF, BBF, UBF, and LBF values were increased, while MBF was decreased, under hypercapnia, and vice versa. The BBF, UBF, and LBF values were increased, while the MBF value was decreased, under hypercapnia during Remi infusion, and vice versa. The BBF, MBF, UBF, and LBF values, but not the CCBF and TBF values, changed along with ETCO2 changes during Remi infusion. PMID:26061573

  15. Tissue Blood Flow During Remifentanil Infusion With Carbon Dioxide Loading.

    PubMed

    Kanbe, Hiroaki; Matsuura, Nobuyuki; Kasahara, Masataka; Ichinohe, Tatsuya

    2015-01-01

    The aim of this study was to investigate the effect of changes in end-tidal carbon dioxide tension (ETCO2) during remifentanil (Remi) infusion on oral tissue blood flow in rabbits. Eight male tracheotomized Japan White rabbits were anesthetized with sevoflurane under mechanical ventilation. The infusion rate of Remi was 0.4 μg/kg/min. Carbon dioxide was added to the inspired gas to change the inspired CO2 tension to prevent changes in the ventilating condition. Observed variables were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), common carotid artery blood flow (CCBF), tongue mucosal blood flow (TBF), mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF). The CCBF, TBF, BBF, UBF, and LBF values were increased, while MBF was decreased, under hypercapnia, and vice versa. The BBF, UBF, and LBF values were increased, while the MBF value was decreased, under hypercapnia during Remi infusion, and vice versa. The BBF, MBF, UBF, and LBF values, but not the CCBF and TBF values, changed along with ETCO2 changes during Remi infusion. PMID:26061573

  16. Removing the confusion about infusion.

    PubMed

    Bayne, C G

    1997-02-01

    There is more to infusion technology than simply connecting the "pump-du-jour" to the central line. The purpose of infusion technology, its safety products and four categories of devices-elastomeric, mechanical, gas and membrane-are discussed. PMID:9287736

  17. Intraosseous infusion and pulmonary fat embolism.

    PubMed

    Hasan, M. Yousuf; Kissoon, Niranjan; Khan, Taj M.; Saldajeno, Virgilio; Goldstein, Jeffrey; Murphy, Suzanne P.

    2001-01-01

    OBJECTIVES: To determine the incidence of pulmonary fat embolism after the intraosseous (IO) infusion of normal saline and drugs and to determine whether pulmonary capillary blood is a predictor of lung fat embolism. DESIGN: A randomized, prospective, animal study. SETTING: Animal research laboratory of a university hospital. SUBJECTS: Twenty-eight mixed breed piglets (average weight 30.9 kg). Interventions and Methods: Animals were anesthetized, intubated, mechanically ventilated, and instrumented. IO needles were placed in the tibial bone. Animals were assigned to one of four groups: Group 1 received fluid (20 mL/kg) under 300 mm Hg pressure (n = 6); group 2 received fluid (20 mL/kg) at free flow under gravity (n = 6); group 3 received 100 mL of fluid over 20 mins (n = 8); and group 4 received 100 mL of fluid over 7 mins (n = 8). MEASUREMENTS AND MAIN RESULTS: Buffy coat samples were obtained from pulmonary arterial catheter in the occluded position at baseline, after IO needle placement, and at the end of infusion. Lung specimens (both upper and lower lobes) were obtained at the end of the infusion. Specimens were stained with oil red O and graded for fat emboli by a pathologist blinded to experimental conditions. Fat emboli (one to three emboli per high power field) were found in about 30% of the lung specimens. The difference in number of fat emboli between groups was not statistically significant. Buffy coat stains yielded fat emboli, which were distributed sporadically in all groups. CONCLUSION: Fat embolism is common; however, the method of IO fluid administration does not influence the number of emboli. Our study therefore implies that the risk of fat embolization is of concern, but its clinical relevance is unclear. Until the clinical significance of pulmonary fat emboli and the prevalence of fat emboli syndrome are delineated more precisely, the IO route is an effective but not necessarily safe route for delivery of fluids and drugs. PMID:12797872

  18. Adjacent central venous catheters can result in immediate aspiration of infused drugs during renal replacement therapy.

    PubMed

    Kam, K Y R; Mari, J M; Wigmore, T J

    2012-02-01

    Dual-lumen haemodiafiltration catheters enable continuous renal replacement therapy in the critically ill and are often co-located with central venous catheters used to infuse drugs. The extent to which infusions are immediately aspirated by an adjacent haemodiafiltration catheter remains unknown. A bench model was constructed to evaluate this effect. A central venous catheter and a haemodiafiltration catheter were inserted into a simulated central vein and flow generated using centrifugal pumps within the simulated vein and haemodiafiltration circuit. Ink was used as a visual tracer and creatinine solution as a quantifiable tracer. Tracers were completely aspirated by the haemodiafiltration catheter unless the infusion was at least 1 cm downstream to the arterial port. No tracer was aspirated from catheters infusing at least 2 cm downstream. Orientation of side ports did not affect tracer elimination. Co-location of central venous and haemodiafiltration catheters may lead to complete aspiration of infusions into the haemodiafilter with resultant drug under-dosing.

  19. Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

    NASA Technical Reports Server (NTRS)

    Kumagai, Kazuhiro; Reid, Ian A.

    1994-01-01

    We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

  20. Intraosseous infusion in pediatric patients.

    PubMed

    Neal, C J; McKinley, D F

    1994-01-01

    In traumatically injured or medically unstable pediatric patients requiring resuscitation, gaining intravenous access often is frustrating for the physician and agonizing for the patient. Even when cardiopulmonary resuscitation is performed by trained professionals, cardiac arrests in children in the prehospital setting have a mortality of 79% to 100%. Immediate vascular access such as that obtained by intraosseous infusion improves survival. The intraosseous infusion technique uses the medullary cavity in the tibia as a "noncollapsible vein" for parenteral infusion. It is indicated in a child in shock or cardiac arrest when two attempts to access peripheral vasculature have failed or when more than 2 minutes have elapsed in the attempt to gain access. Epinephrine, bicarbonate, calcium, lidocaine, and volume expanders can be infused via the intraosseous route. Complications rarely occur. The technique described here is gaining acceptance in both prehospital and emergency department settings. PMID:8169160

  1. Inhibitors of urokinase reduce size of prostate cancer xenografts in severe combined immunodeficient mice.

    PubMed

    Jankun, J; Keck, R W; Skrzypczak-Jankun, E; Swiercz, R

    1997-02-15

    Proteolytic enzymes are required to mediate tumor cell invasion and metastasis. The urokinase plasminogen activator (uPA) is commonly overexpressed by many human cancers. Therefore, uPA is a logical target to inhibit cancer invasion and metastasis. However, uPA inhibitors also reduce tumor growth. We used a mutated form of plasminogen activator inhibitor type 1 to conform a correlation between the inactivation of uPA and tumor size; we have compared these results with the action of p-aminobenzamidine and amiloride, known inhibitors of uPA. Our results show that blocking uPA by uPA inhibitors reduces tumor size in experimental animals. Our molecular simulation of docking inhibitors to the urokinase reveals that all tested small molecule inhibitors bind in proximity of uPA's specificity pocket, a critical site for future search of novel anticancer uPA inhibitors. PMID:9044824

  2. Proteolytic regulation of epithelial sodium channels by urokinase plasminogen activator: cutting edge and cleavage sites.

    PubMed

    Ji, Hong-Long; Zhao, Runzhen; Komissarov, Andrey A; Chang, Yongchang; Liu, Yongfeng; Matthay, Michael A

    2015-02-27

    Plasminogen activator inhibitor 1 (PAI-1) level is extremely elevated in the edematous fluid of acutely injured lungs and pleurae. Elevated PAI-1 specifically inactivates pulmonary urokinase-type (uPA) and tissue-type plasminogen activators (tPA). We hypothesized that plasminogen activation and fibrinolysis may alter epithelial sodium channel (ENaC) activity, a key player in clearing edematous fluid. Two-chain urokinase (tcuPA) has been found to strongly stimulate heterologous human αβγ ENaC activity in a dose- and time-dependent manner. This activity of tcuPA was completely ablated by PAI-1. Furthermore, a mutation (S195A) of the active site of the enzyme also prevented ENaC activation. By comparison, three truncation mutants of the amino-terminal fragment of tcuPA still activated ENaC. uPA enzymatic activity was positively correlated with ENaC current amplitude prior to reaching the maximal level. In sharp contrast to uPA, neither single-chain tPA nor derivatives, including two-chain tPA and tenecteplase, affected ENaC activity. Furthermore, γ but not α subunit of ENaC was proteolytically cleaved at ((177)GR↓KR(180)) by tcuPA. In summary, the underlying mechanisms of urokinase-mediated activation of ENaC include release of self-inhibition, proteolysis of γ ENaC, incremental increase in opening rate, and activation of closed (electrically "silent") channels. This study for the first time demonstrates multifaceted mechanisms for uPA-mediated up-regulation of ENaC, which form the cellular and molecular rationale for the beneficial effects of urokinase in mitigating mortal pulmonary edema and pleural effusions.

  3. Structural Basis of Interaction Between Urokinase-type Plasminogen Activator and its Receptor

    SciTech Connect

    Barinka,C.; Parry, G.; Callahan, J.; Shaw, D.; Kuo, A.; Cines, B.; Mazar, A.; Lubkowski, J.

    2006-01-01

    Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 {angstrom}. We report the 1.9 {angstrom} crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding.

  4. Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion

    PubMed Central

    Limberg, Jacqueline K.; Kellawan, J. Mikhail; Harrell, John W.; Johansson, Rebecca E.; Eldridge, Marlowe W.; Proctor, Lester T.; Sebranek, Joshua J.

    2014-01-01

    We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise − rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = −0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. PMID:25038148

  5. Regional blood flow during continuous low-dose endotoxin infusion

    SciTech Connect

    Fish, R.E.; Lang, C.H.; Spitzer, J.A.

    1986-01-01

    Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Cardiac output and regional blood flow were determined by the radiolabeled microsphere method after 6 and 30 hr of ET or saline infusion. Cardiac output (CO) of ET rats was not different from time-matched controls, whereas arterial pressure was 13% lower after 30 hr of infusion. After both 6 and 30 hr of ET, pancreatic blood flow and percentage of cardiac output were lower than in controls. Estimated portal venous flow was decreased at each time point, and an increased hepatic arterial flow (significant after 30 hr) resulted in an unchanged total hepatic blood flow. Blood flow to most other tissues, including epididymal fat, muscle, kidneys, adrenals, and gastrointestinal tract, was similar between treatments. Maintenance of blood flow to metabolically important tissues indicates that the previously reported alterations in in vitro cellular metabolism are not due to tissue hypoperfusion. Earlier observations of in vitro myocardial dysfunction, coexistent with the significant impairment in pancreatic flow, raise the possibility that release of a myocardial depressant factor occurs not only in profound shock but also under less severe conditions of sepsis and endotoxemia.

  6. Determinants of oxygen uptake during sodium bicarbonate infusion.

    PubMed

    Patterson, R W; Sullivan, S F

    1978-09-01

    Steady-state passive hyperventilation alkalosis produces a predictable increase in oxygen uptake (VO2) proportional to the change in arterial pH (pHa) while variable changes in VO2 have been reported during alkali infusion. To compare metabolic with respiratory alkalosis 17 dogs were anesthetized with halothane and their VO2 response to respiratory alkalosis evaluated by hyperventilation. The pHa measured during this phase was duplicated during the later continuous infusion of NaHCO3 at which time either 1) ventilation was held constant at the control level, allowing arterial carbon dioxide tension (PaCO2) to rise as a consequence of the bicarbonate dissociation, or 2) PaCO2 was held constant by servo control of ventilation. Hyperventilation (pHa 7.6, PaCO2 13 Torr) produced an average increase in VO2 of 24%. During the bicarbonate infusion at constant ventilation (pHa 7.6, PaCO2 45 Torr) VO2 increased only 7%; however, when PACO2 was held constant by servo ventilation VO2 increased 21% above control. We conclude that respiratory and metabolic alkalosis produce similar increases in VO2 when steady-state acid-base conditions are achieved. PMID:29867

  7. Cineangiography of the Coronary Arteries

    PubMed Central

    Tremblay, Gerard M.; Charland, Raymond; Roy, Paul; Primeau, Robert; Nadeau, Reginald

    1971-01-01

    Fifty French-Canadian patients presenting with typical or atypical anginal pain were studied by selective cinearteriography and coronary sinus catheterization, with measurement of myocardial function, oxygen and lactate extraction at rest and during isoproterenol infusion. In 28 of 42 patients all three coronary arteries were involved, but angina pectoris also occurred in patients with single mildly stenotic arterial lesions and even in eight patients with normal cinearteriograms. All patients with severe arterial lesions had typical angina, and the longer the duration of angina, the greater the extent, usually, of anatomic disease. Seventy-nine percent of resting electrocardiograms of patients with documented coronary artery disease were abnormal, with recognizable prior infarction in 18. Two-thirds of the patients experiencing pain during the stressful state had abnormal ventricular function. An abnormal arteriovenous lactate difference in response to isoproterenol occurred in patients in all groups. PMID:5563346

  8. A theoretical alternative intraosseous infusion site in severely hypovolemic children

    PubMed Central

    van Schoor, Albert-Neels; Bosman, Marius C.

    2015-01-01

    Background Studies have shown that the venous system tends to collapse during hypovolemic shock. The use of the bone marrow space for infusions is an effective alternative, with the tibial insertion site being the norm. Objectives This study was conducted to determine a quick intraosseous infusion method that could be an alternative to the tibial route in neonates during emergency situations. Method A sample of 30 neonatal cadavers was dissected to explore a possible alternative to the tibial insertion site. The needle was inserted in the superolateral aspect of the humerus. The needle infusion site was then dissected to determine possible muscular and neurovascular damage that might occur during the administration of this procedure, with the greatest concern being the posterior circumflex humeral artery and axillary nerve exiting the quadrangular space. The distance of the needle insertion site was measured in relation to the soft tissue as well as to bony landmarks. Results The calculated 95% confidence interval shows that the needle can be safely inserted into the intraosseous tissue at the greater tubercle of the humerus 9.5 mm – 11.1 mm from the acromion. This is about a little finger’s width from the acromioclavicular joint. Conclusion Anatomically, the described site is suggested to offer a safe alternative access point for emergency infusion in severely hypovolemic newborns and infants, without the risk of damage to any anatomical structures. PMID:26245618

  9. Compartment syndrome following intraosseous infusion.

    PubMed

    Moen, Todd C; Sarwark, John F

    2008-08-01

    Intraosseous infusion is a valuable technique in the resuscitation of critically ill pediatric patients in whom vascular access has proved otherwise impossible. Although it is well established as a safe and reliable means of emergent access, intraosseous infusion is not without danger, nor complication. One of the rare yet most grave complications of intraosseous access is compartment syndrome. We report a case of compartment syndrome as a result of intraosseous infusion that serves to remind of the potential pitfalls of this technique. An otherwise healthy 6-year-old girl presented to our institution's pediatric intensive care unit following emergent resuscitation for a prolonged cardiac arrest. Approximately 1 hour following an uneventful soccer practice, without any antecedent cardiopulmonary symptoms or complaints, the patient collapsed and was unresponsive, not breathing, and pulseless. In the course of resuscitation, right and left tibial intraosseous lines were started. After 30 minutes of resuscitation, with multiple rounds of lidocaine and epinephrine infused through the intraosseous lines, a sustained perfusing rhythm was established. Acute compartment syndrome was diagnosed, and through anterolateral and posteromedial incisions, all 4 fascial compartments were released. While the condition of the patient's extremity improved, the overall clinical condition of the patient did not. This case highlights the fundamental principles regarding the use of intraosseous infusion and the diagnosis and management of compartment syndrome in critically ill patients. PMID:19292404

  10. Use of Continuous Infusion Hydralazine in a Pediatric Patient on Mechanical Circulatory Support.

    PubMed

    Dillman, Nicholas O; Anders, Marc M; Moffett, Brady S

    2016-01-01

    Hydralazine is a direct peripheral arterial vasodilator used for acute hypertension. Usually administered as a bolus dose, continuous infusion has been described during pregnancy for preeclampsia and eclampsia and in limited reports in cardiac surgeries for afterload reduction. This case describes the use of continuous infusion hydralazine for afterload reduction in an infant receiving extracorporeal membrane oxygenation (ECMO) post-cardiac surgery. Postsurgery, the patient's mean arterial pressures (MAPs) could not be controlled despite escalating doses of vasodilatory medications including nitroprusside, nicardipine, and milrinone; hence, continuous infusion hydralazine was initiated. Although the initiation of a hydralazine infusion produced a decrease in MAP, the response was unsustainable. This case highlights an alternative method for managing systemic vascular resistance and cardiac output to allow for myocardial recovery after cardiac surgery and use of extracorporeal support. At the time of this writing, this is the first published case describing hydralazine administration via continuous infusion in pediatric patients. The use of continuous infusion hydralazine for afterload reduction provided a brief, non-sustained reduction in MAP in a post-cardiac surgery infant managed on ECMO support.

  11. Use of Continuous Infusion Hydralazine in a Pediatric Patient on Mechanical Circulatory Support

    PubMed Central

    Dillman, Nicholas O.; Anders, Marc M.

    2016-01-01

    Hydralazine is a direct peripheral arterial vasodilator used for acute hypertension. Usually administered as a bolus dose, continuous infusion has been described during pregnancy for preeclampsia and eclampsia and in limited reports in cardiac surgeries for afterload reduction. This case describes the use of continuous infusion hydralazine for afterload reduction in an infant receiving extracorporeal membrane oxygenation (ECMO) post–cardiac surgery. Postsurgery, the patient's mean arterial pressures (MAPs) could not be controlled despite escalating doses of vasodilatory medications including nitroprusside, nicardipine, and milrinone; hence, continuous infusion hydralazine was initiated. Although the initiation of a hydralazine infusion produced a decrease in MAP, the response was unsustainable. This case highlights an alternative method for managing systemic vascular resistance and cardiac output to allow for myocardial recovery after cardiac surgery and use of extracorporeal support. At the time of this writing, this is the first published case describing hydralazine administration via continuous infusion in pediatric patients. The use of continuous infusion hydralazine for afterload reduction provided a brief, non-sustained reduction in MAP in a post–cardiac surgery infant managed on ECMO support. PMID:27453704

  12. Effects of methacholine infusion on desflurane pharmacokinetics in piglets.

    PubMed

    Kozian, Alf; Kretzschmar, Moritz; Baumgardner, James E; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2015-12-01

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (V T)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and

  13. Effects of methacholine infusion on desflurane pharmacokinetics in piglets☆

    PubMed Central

    Kozian, Alf; Kretzschmar, Moritz; Baumgardner, James E.; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2015-01-01

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (VT)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and

  14. Microcomputer Infusion Project: A Model.

    ERIC Educational Resources Information Center

    Rossberg, Stephen A.; Bitter, Gary G.

    1988-01-01

    Describes the Microcomputer Infusion Project (MIP), which was developed at Arizona State University to provide faculty with the necessary hardware, software, and training to become models of computer use in both lesson development and presentation for preservice teacher education students. Topics discussed include word processing; database…

  15. Enhancing Instruction through Software Infusion.

    ERIC Educational Resources Information Center

    Sia, Archie P.

    The presence of the computer in the classroom is no longer considered an oddity; it has become an ordinary resource for teachers to use for the enhancement of instruction. This paper presents an examination of software infusion, i.e., the use of computer software to enrich instruction in an academic curriculum. The process occurs when a chosen…

  16. Infusing Culture in Career Counseling

    ERIC Educational Resources Information Center

    Arthur, Nancy; Collins, Sandra

    2011-01-01

    This article introduces the culture-infused career counselling (CICC) model. Six principles are foundational to a tripartite model emphasizing cultural self-awareness, awareness of client cultural identities, and development of a culturally sensitive working alliance. The core competencies ensure the cultural validity and relevance of career…

  17. Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro

    PubMed Central

    Wilson, A; Gibson, P

    2000-01-01

    BACKGROUND—Migration of colonic epithelial cells is important for mucosal repair following injury. The urokinase (u-PA) system regulates migration in other cell types.
AIM—To examine the role of u-PA and its receptor (u-PAR) in colonic epithelial cell migration.
METHODS—Migration was assessed over 24 hours in circular wounds made in confluent monolayers of LIM1215 and Caco-2 human colon cancer cells. The function of u-PA and u-PAR was ablated with antisense oligonucleotides to block expression, with synthetic u-PA peptides to block interaction, and with aprotinin to block u-PA mediated proteolysis.
RESULTS—Migration was stimulated two to threefold by exogenous u-PA, an effect dependent on u-PAR binding but independent of u-PA mediated mitogenesis and proteolysis. Expression of u-PA and u-PAR was inhibited by 80% by the appropriate antisense oligonucleotide. Basal migration and the motogenic effects of butyrate, epidermal growth factor, and phorbol-12-myristate-13-acetate were suppressed by the u-PAR antisense oligonucleotide (40-60%) but were at best minimally affected following inhibition of u-PA expression and binding. 
CONCLUSIONS—In an in vitro model of wounded colonic epithelium, u-PAR promotes cell migration through mechanisms that are not exclusively dependent on u-PA binding. Therefore, u-PA and u-PAR may contribute to colonic mucosal repair in vivo.


Keywords: colon; migration; urokinase; urokinase receptor; epidermal growth factor; butyrate; protein kinase C PMID:10861271

  18. Acute arterial occlusion - kidney

    MedlinePlus

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... main artery to the kidney is called the renal artery. Reduced blood flow through the renal artery ...

  19. Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

    SciTech Connect

    Yang, Shuofei Liu, Baochen Ding, Weiwei He, Changsheng Wu, Xingjiang Li, Jieshou

    2015-02-15

    PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.

  20. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or...

  1. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or...

  2. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or...

  3. The effect of saline and hyperoncotic dextran infusion on canine ileal salt and water absorption and regional blood flow.

    PubMed

    Mailman, D; Jordan, K

    1975-10-01

    1. The unidirectional Na and H2O fluxes, vascular pressures and total and absorptive site blood flows in the canine ileum were determined before and during I.V. saline infusion and subsequent I.V. infusion of hyperoncotic dextran. The intestinal perfusion solutions were isotonic saline or isotonic saline and mannitol, but the effects of I.V. saline or I.V. hyperoncotic dextran infusion were generally the same for both luminal solutions. 2. Continuous I.V. infusion of saline caused a continuous increase in the unidirectional flux of Na and H2O into the ileal lumen, an increase in total blood flow, and an increase in venous pressure. 3. The net absorption of Na and H2O was decreased by I.V. saline infusion. 4. The unidirectional fluxes of Na and H2O out of the lumen, arterial pressure, and absorptive site blood flow were not affected by I.V. saline infusion. 5. I.V. hyperoncotic dextran infusion reversed most of the effects of saline infusion. 6. The unidirectional fluxes of Na and H2O into the lumen were significantly correlated with Starling forces during I.V. saline infusion. 7. It was concluded that intestinal transport of salt and water was subject to regulation by physical forces at the capillary level.

  4. Changes in urinary water and electrolyte excretion in sodium-loaded sheep in response to intravenous infusion of arginine vasopressin.

    PubMed

    Scott, D; Morton, J J

    1976-01-01

    Mature sheep receiving supplements of sodium chloride into the rumen were given intravenous infusions of arginine vasopressin at rates varying from 4-6-23 pmol/min (2-10 mU/min). Infusion of the hormone led to an increase in urine flow and to increases in the amounts of sodium and chloride excreted, the effect on flow was, however, the greater so that the osmolality of the urine fell during the infusions. In sheep given intravenous infusions of a hypertonic sodium chloride solution addition of vasopressin to the infusate led to the formation of a larger volume of urine containing a higher proportion of the infused salt load compared to when the salt solution alone was given. As before the effect on flow was the greater and hence the osmolality of the urine was lower when the hormone was given. In other experiments intravenous infusion of a hypertonic sodium chloride solution at rates providing 2-8 mmol NaCl/min led to increases in urine flow and increases in sodium and chloride excretion, the size of these increases being proportional to infusion rate. Plasma vasopressin levels markedly increased during these infusions, the levels seen being similar to those seen in sheep given vasopressin in amounts which increased both urine flow and electrolyte excretion. This suggests that during hypertonic salt loading vasopressin probably contributes directly to the increases in urine flow and the increases in electrolyte excretion which are seen. Further evidence in support of this was obtained in experiments in which a greater natriuretic response was seen in sheep given a hypertonic sodium chloride solution into the carotid artery as opposed to the given a hypertonic sodium chloride solution into the carotid artery as opposed to the jugular vein and where it was shown that plasma vasopressin levels were indeed higher when the solution was given into the artery.

  5. Axillary artery compression and thrombosis in throwing athletes.

    PubMed

    Rohrer, M J; Cardullo, P A; Pappas, A M; Phillips, D A; Wheeler, H B

    1990-06-01

    A 28-year-old major league baseball pitcher sustained an axillary artery thrombosis which was successfully treated with intraarterial urokinase. Subsequent angiography and duplex scanning with the arm elevated in the pitching position demonstrated inducible compression of the axillary artery by the humeral head as well as compression at the thoracic outlet. To determine the incidence of axillary and subclavian artery compression and to investigate the mechanism of injury, brachial artery blood pressures and duplex scans of the subclavian and axillary arteries were performed in both the neutral position and the throwing position in the 92 extremities of 19 major league baseball pitchers, 16 non-pitching major league players, and 11 nonathlete controls. A drop in blood pressure of greater than 20 mm Hg was noted in the position in 56% of extremities tested, with a loss of a detectable blood pressure in 13%. Compression of the axillary artery by the humeral head was documented in 83% of extremities, but in only 7.6% was a greater than 50% stenosis inducible. No statistical difference was found in the incidence of arterial compression between the three groups tested or between their dominant and nondominant extremities. Dissection of the axillary artery in two cadavers documented that abduction and external rotation of the arm causes compression of the axillary artery by the humeral head, which acts as a fulcrum. We conclude that the repetitive mechanical trauma of the throwing motion can cause intermittent compression and contusion of the axillary artery by the humeral head and predisposes the athlete who throws to thrombosis of the axillary artery.

  6. Urokinase-like plasminogen activator receptor expression on disseminated breast cancer cells.

    PubMed

    Tögel, F; Datta, C; Badbaran, A; Kröger, N; Renges, H; Gieseking, F; Jänicke, F; Zander, A R; Krüger, W

    2001-02-01

    Disseminated tumor cells are detected frequently in bone marrow, peripheral blood, and cytokine-mobilized peripheral blood cell products of women undergoing high-dose therapy for breast cancer. Several attempts were made to purge autografts from contaminating cancer cells; however, the biological and clinical impact of these contaminations has not been clarified so far. Expression of distinct phenotypes is a surrogate marker for metastatic behavior of cancer cells. The expression of the urokinase-like plasminogen activator receptor seems to be a factor of high importance. It is not expressed by normal mammary tissue. Disseminated cancer cells from marrow, blood, and stem cell products have been investigated by double-stain technique for urokinase-like plasminogen activator receptor (uPA-R) expressing cytokeratin-positive cells. uPA-R(+)/CK(+) cells could be found in all qualities of samples; however, significantly less in G-CSF-mobilized peripheral blood stem cells compared to samples of other provenance (p = 0.02). It can be concluded that epithelial cells of malignant phenotype occur in blood, marrow, and autografts of breast cancer patients. Populations of disseminated tumor cells are phenotypically heterogeneous. Reduced uPA-R expression on cancer cells from leukapheresis samples might suggest a less aggressive nature of these cells compared to disseminated cells found in bone marrow. Furthermore, the data suggest that the phenotype of tumor cell contamination in leukapheresis products differs significantly from those of disseminated cancer cells in bone marrow or blood.

  7. Pulmonary vascular resistance during lipid infusion in neonates.

    PubMed Central

    Prasertsom, W.; Phillipos, E. Z.; Van Aerde, J. E.; Robertson, M.

    1996-01-01

    Using two-dimensional echocardiography, pulmonary vascular resistance was estimated from right ventricular pre-ejection period to ejection time (RVPEP/ET) in 11 preterm infants with respiratory distress, to test the effect of different doses of continuous lipid infusion. Echocardiography was performed at baseline with no lipid infusing 2 and 24 hours after 1.5 and 3 g/kg/day of intravenous lipid, 24 hours after discontinuing intravenous lipid emulsion, and 2 hours after restarting intravenous lipid. After 24 hours of intravenous lipid at 1.5 g/kg/day the RVPEP/ET rose to mean (SD) 0.287 (0.03) from a baseline value of 0.225 (0.02) and to 0.326 (0.05) after 24 hours of intravenous lipid at 3 g/kg/day. Pulmonary arterial pressure returned to baseline 24 hours after the intravenous lipid had been discontinued. Continuous 24 hour infusion of lipid caused significant dose and time-dependent increases in pulmonary vascular resistance. Intravenous lipid may aggravate pulmonary hypertension. PMID:8777674

  8. Dual functionality of phosphonic-acid-appended phthalocyanines: inhibitors of urokinase plasminogen activator and anticancer photodynamic agents.

    PubMed

    Venkatramaiah, N; Pereira, Patrícia M R; Almeida Paz, Filipe A; Ribeiro, Carlos A F; Fernandes, Rosa; Tomé, João P C

    2015-11-01

    Phthalocyanines (Pcs) bearing phosphonic acid groups at the periphery exhibit a potential photodynamic effect to induce phototoxicity on human bladder cancer epithelial cells (UM-UC-3). In vitro photophysical and biological studies show high intrinsic ability to inhibit the activity of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9).

  9. The Heparin-Induced Thrombocytopenia and Thrombosis Syndrome: Treatment with Intraarterial Urokinase and Systemic Platelet Aggregation Inhibitors

    SciTech Connect

    Murphy, Kenneth D.; McCrohan, Gerard; DeMarta, Deborah A.; Shirodkar, Nitin B.; Kwon, Oun J.; Chopra, Paramjit S.

    1996-03-15

    We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin.

  10. Prolonged adenosine triphosphate infusion and exercise hyperemia in humans.

    PubMed

    Shepherd, John R A; Joyner, Michael J; Dinenno, Frank A; Curry, Timothy B; Ranadive, Sushant M

    2016-09-01

    In humans, intra-arterial ATP infusion in limbs mimics many features of exercise hyperemia. However, it remains unknown whether ATP can evoke the prolonged vasodilation seen during exercise. Therefore, we addressed two questions during a continuous 3-h brachial artery infusion of ATP [20 μg·100 ml forearm volume (FAV)(-1)·min(-1)]: 1) would skeletal muscle blood flow remain robust or wane over time (tachyphylaxis); and 2) would the hyperemic response to moderate-intensity exercise performed during the ATP administration be blunted compared with that during control (saline) infusion. Nine participants (25 ± 1 yr) performed one trial consisting of seven bouts of rhythmic handgrip exercise (20 contractions/min at 20% of maximum), two bouts during saline (control), and five bouts during 180 min of continuous ATP infusion. Five minutes of ATP infusion resulted in a 710% increase in forearm vascular conductance (FVC) from control (4.8 ± 0.77 vs. 35.0 ± 5.7 ml·min(-1)·100 mmHg(-1)·dl FAV(-1), P < 0.05). Contrary to our expectations, FVC did not wane over time with values of 35.0 ± 5.7 and 36.0 ± 7.7 ml·min(-1)·100 mmHg(-1)·dl FAV(-1) (P > 0.05), seen prior to the exercise bouts at 5 vs. 150 min, respectively. During superimposed exercise, FVC increased from 35.0 ± 5.7 to 49.6 ± 5.4 ml·min(-1)·100 mmHg(-1)·dl FAV(-1) at 5 min and 36.0 ± 7.7 to 54.5 ± 5.0 at 150 min (P < 0.05). Our findings demonstrate ATP vasodilation is prolonged over time without tachyphylaxis; however, exercise hyperemia responses remain intact. Our results challenge the metabolic theory of exercise hyperemia, suggesting a disconnect between matching of blood flow and metabolic demand. PMID:27445304

  11. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  12. Continuous Intra-Arterial Nimodipine for the Treatment of Cerebral Vasospasm

    SciTech Connect

    Mayer, Thomas E.; Dichgans, Martin; Straube, Andreas; Birnbaum, Tobias; Mueller-Schunk, Stephanie; Hamann, Gerhard F.; Schulte-Altedorneburg, Gernot

    2008-11-15

    Two patients with refractory symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) were treated by continuous intra-arterial nimodipine infusion via a catheter placed in the internal carotid artery or vertebral artery for 3 and 12 days, respectively. Recovery of the neurological deficits, normalization of MR perfusion, a decrease in the elevated mean flow velocity measured by transcranial duplex sonography, and angiographic recanalization were observed. Continuous intra-arterial nimodipine might be a treatment option in severe refractory vasospasm following SAH.

  13. The Safety of Target-Controlled Infusions.

    PubMed

    Schnider, Thomas W; Minto, Charles F; Struys, Michel M R F; Absalom, Anthony R

    2016-01-01

    Target-controlled infusion (TCI) technology has been available in most countries worldwide for clinical use in anesthesia for approximately 2 decades. This infusion mode uses pharmacokinetic models to calculate infusion rates necessary to reach and maintain the desired drug concentration. TCI is computationally more complex than traditional modes of drug administration. The primary difference between TCI and conventional infusions is that TCI decreases the infusion rate at regular intervals to account for the uptake of drug into saturable compartments. Although the calculated infusion rates are consistent with manually controlled infusion rates, there are concerns that TCI administration of IV anesthetics could introduce unique safety concerns. After approximately 2 decades of clinical use, it is appropriate to assess the safety of TCI. Our aim in this article was to describe safety-relevant issues related to TCI, which should have emerged after its use in millions of patients. We collected information from published medical literature, TCI manufacturers, and publicly available governmental Web sites to find evidence of safety issues with the clinical use of TCI. Although many case reports emphasize that IV anesthesia is technically more demanding than inhaled anesthesia, including human errors associated with setting up IV infusions, no data suggest that a TCI mode of drug delivery introduces unique safety issues other than selecting the wrong pharmacokinetic model. This is analogous to the risk of selecting the wrong drug with current infusion pumps. We found no evidence that TCI is not at least as safe as anesthetic administration using constant rate infusions. PMID:26516801

  14. Cardiovascular effects of dobutamine and phenylephrine infusion in sevoflurane-anesthetized Thoroughbred horses.

    PubMed

    Ohta, Minoru; Kurimoto, Shinjiro; Ishikawa, Yuhiro; Tokushige, Hirotaka; Mae, Naomi; Nagata, Shun-ichi; Mamada, Masayuki

    2013-11-01

    To determine dose-dependent cardiovascular effects of dobutamine and phenylephrine during anesthesia in horses, increasing doses of dobutamine and phenylephrine were infused to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and infused 3 increasing doses of dobutamine (0.5, 1.0 and 2.0 µg/kg/min) for 15 min each dose. Following to 30 min of reversal period, 3 increasing doses of phenylephrine (0.25, 0.5 and 1.0 µg/kg/min) were infused. Cardiovascular parameters were measured before and at the end of each 15-min infusion period for each drug. Blood samples were collected every 5 min during phenylephrine infusion period. There were no significant changes in heart rate throughout the infusion period. Both dobutamine and phenylephrine reversed sevoflurane-induced hypotension. Dobutamine increased both mean arterial blood pressure (MAP) and cardiac output (CO) as the result of the increase in stroke volume, whereas phenylephrine increased MAP but decreased CO as the result of the increase in systemic vascular resistance. Plasma phenylephrine concentration increased dose-dependently, and these values at 15, 30 and 45 min were 6.2 ± 1.2, 17.0 ± 4.8 and 37.9 ± 7.3 ng/ml, respectively.

  15. Cardiovascular effects of dobutamine and phenylephrine infusion in sevoflurane-anesthetized Thoroughbred horses.

    PubMed

    Ohta, Minoru; Kurimoto, Shinjiro; Ishikawa, Yuhiro; Tokushige, Hirotaka; Mae, Naomi; Nagata, Shun-ichi; Mamada, Masayuki

    2013-11-01

    To determine dose-dependent cardiovascular effects of dobutamine and phenylephrine during anesthesia in horses, increasing doses of dobutamine and phenylephrine were infused to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and infused 3 increasing doses of dobutamine (0.5, 1.0 and 2.0 µg/kg/min) for 15 min each dose. Following to 30 min of reversal period, 3 increasing doses of phenylephrine (0.25, 0.5 and 1.0 µg/kg/min) were infused. Cardiovascular parameters were measured before and at the end of each 15-min infusion period for each drug. Blood samples were collected every 5 min during phenylephrine infusion period. There were no significant changes in heart rate throughout the infusion period. Both dobutamine and phenylephrine reversed sevoflurane-induced hypotension. Dobutamine increased both mean arterial blood pressure (MAP) and cardiac output (CO) as the result of the increase in stroke volume, whereas phenylephrine increased MAP but decreased CO as the result of the increase in systemic vascular resistance. Plasma phenylephrine concentration increased dose-dependently, and these values at 15, 30 and 45 min were 6.2 ± 1.2, 17.0 ± 4.8 and 37.9 ± 7.3 ng/ml, respectively. PMID:23832627

  16. Cardiovascular Effects of Dobutamine and Phenylephrine Infusion in Sevoflurane-anesthetized Thoroughbred Horses

    PubMed Central

    OHTA, Minoru; KURIMOTO, Shinjiro; ISHIKAWA, Yuhiro; TOKUSHIGE, Hirotaka; MAE, Naomi; NAGATA, Shun-ichi; MAMADA, Masayuki

    2013-01-01

    ABSTRACT To determine dose-dependent cardiovascular effects of dobutamine and phenylephrine during anesthesia in horses, increasing doses of dobutamine and phenylephrine were infused to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and infused 3 increasing doses of dobutamine (0.5, 1.0 and 2.0 µg/kg/min) for 15 min each dose. Following to 30 min of reversal period, 3 increasing doses of phenylephrine (0.25, 0.5 and 1.0 µg/kg/min) were infused. Cardiovascular parameters were measured before and at the end of each 15-min infusion period for each drug. Blood samples were collected every 5 min during phenylephrine infusion period. There were no significant changes in heart rate throughout the infusion period. Both dobutamine and phenylephrine reversed sevoflurane-induced hypotension. Dobutamine increased both mean arterial blood pressure (MAP) and cardiac output (CO) as the result of the increase in stroke volume, whereas phenylephrine increased MAP but decreased CO as the result of the increase in systemic vascular resistance. Plasma phenylephrine concentration increased dose-dependently, and these values at 15, 30 and 45 min were 6.2 ± 1.2, 17.0 ± 4.8 and 37.9 ± 7.3 ng/ml, respectively. PMID:23832627

  17. Microcirculatory Response In Vivo on Local Intraarterial Infusion of Autogenic Adipose-derived Stem Cells or Stromal Vascular Fraction

    PubMed Central

    2016-01-01

    Background: Both adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) have been demonstrated to have regenerative properties with therapeutic potential for numerous diseases through local or topical applications. However, it is unclear whether ASC or SVF can be delivered systemically through an intra-arterial infusion. The purpose of this study was to examine the microcirculatory response in vivo on local intraarterial infusion of autogenic ASCs or SVF in a vascular pedicle isolated rat cremaster microcirculation model. Materials and Methods: Fat tissue was surgically harvested from the flanks of male Sprague–Dawley rats (n = 12) and processed for SVF isolation. Some SVF samples were cultured for 24 hours for ASC purification. The autogenic SVF (1 × 105) cells (n = 6) or purified ASC (1 × 105) cells (n = 6) cells were infused into the microcirculation of cremaster muscle at a speed of 0.05 mL/min through the cannulation of femoral artery. As this is a vascular pedicle isolated preparation, the infused SVF or ASC cells went nowhere but the cremaster muscle. The video image of the microcirculation was monitored in real time during infusion. Results: Arteriole diameter was measured as A1 (100–160 µm), A2 (40–80 µm), and A3/A4 (10–30 µm). Capillary perfusion was quantified in 18 capillary fields of each muscle. There was a significant increase in the diameter of terminal arterioles (P = 0.049) and the capillary density (P = 0.02) after ASC intraarterial infusion. However, a significant cell aggregation, embolisms, and arterial obstruction were observed in the microcirculation in every case during SVF infusion. Conclusions: Intraarterial infusion is an appropriate route for the delivery of autogenic ASCs, but not of SVF. SVF-induced microembolisms were the reason for narrowing or blocking the lumen of terminal arterioles, resulting in no flow in the corresponding capillaries. PMID:27757364

  18. Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells

    SciTech Connect

    Not Available

    1986-01-05

    The effects of bacterial lipopolysaccharide (endotoxin) on the fibrinolytic activity of bovine pulmonary artery endothelial cells were examined. Endotoxin suppressed the net fibrinolytic activity of cell extracts and conditioned media in a dose-dependent manner. The effects of endotoxin required at least 6 h for expression. Cell extracts and conditioned media contained a 44-kDa urokinase-like plasminogen activator. Media also contained multiple plasminogen activators with molecular masses of 65-75 and 80-100 kDa. Plasminogen activators in extracts and media were unchanged by treatment of cells with endotoxin. Diisopropyl fluorophosphate (DFP)-abolished fibrinolytic activity of extracts and conditioned media. DFP-treated samples from endotoxin-treated but not untreated cells inhibited urokinase and tissue plasminogen activator, but not plasmin. Inhibitory activity was lost by incubation at pH 3 or heating to 56/sup 0/C for 10 min. These treatments did not affect inhibitory activity of fetal bovine serum. Incubation of /sup 125/I-urokinase with DFP-treated medium from endotoxin-treated cells produced an inactive complex with an apparent molecular mass of 80-85 kDa.

  19. Muscle interstitial ATP and norepinephrine concentrations in the human leg during exercise and ATP infusion.

    PubMed

    Mortensen, Stefan P; González-Alonso, José; Nielsen, Jens-Jung; Saltin, Bengt; Hellsten, Ylva

    2009-12-01

    ATP has been proposed to play multiple roles in local skeletal muscle blood flow regulation by inducing vasodilation and modulating sympathetic vasoconstrictor activity, but the mechanisms remain unclear. Here we evaluated the effects of arterial ATP infusion and exercise on leg muscle interstitial ATP and norepinephrine (NE) concentrations to gain insight into the interstitial and intravascular mechanisms by which ATP causes muscle vasodilation and sympatholysis. Leg hemodynamics and muscle interstitial nucleotide and NE concentrations were measured during 1) femoral arterial ATP infusion (0.42 +/- 0.04 and 2.26 +/- 0.52 micromol/min; mean +/- SE) and 2) one-leg knee-extensor exercise (18 +/- 0 and 37 +/- 2 W) in 10 healthy men. Arterial ATP infusion and exercise increased leg blood flow (LBF) in the experimental leg from approximately 0.3 l/min at baseline to 4.2 +/- 0.3 and 4.6 +/- 0.5 l/min, respectively, whereas it was reduced or unchanged in the control leg. During arterial ATP infusion, muscle interstitial ATP, ADP, AMP, and adenosine concentrations remained unchanged in both legs, but muscle interstitial NE increased from approximately 5.9 nmol/l at baseline to 8.3 +/- 1.2 and 8.7 +/- 0.7 nmol/l in the experimental and control leg, respectively (P < 0.05), in parallel to a reduction in arterial pressure (P < 0.05). During exercise, however, interstitial ATP, ADP, AMP, and adenosine concentrations increased in the contracting muscle (P < 0.05), but not in inactive muscle, whereas interstitial NE concentrations increased similarly in both active and inactive muscles. These results suggest that the vasodilatory and sympatholytic effects of intraluminal ATP are mainly mediated via endothelial purinergic receptors. Intraluminal ATP and muscle contractions appear to modulate sympathetic nerve activity by inhibiting the effect of NE rather than blunting its local concentration. PMID:19797688

  20. Crystal structure of the urokinase receptor in a ligand-free form.

    PubMed

    Xu, Xiang; Gårdsvoll, Henrik; Yuan, Cai; Lin, Lin; Ploug, Michael; Huang, Mingdong

    2012-03-01

    The urokinase receptor urokinase-type plasminogen activator receptor (uPAR) is a surface receptor capable of not only focalizing urokinase-type plasminogen activator (uPA)-mediated fibrinolysis to the pericellular micro-environment but also promoting cell migration and chemotaxis. Consistent with this multifunctional role, uPAR binds several extracellular ligands, including uPA and vitronectin. Structural studies suggest that uPAR possesses structural flexibility. It is, however, not clear whether this flexibility is an inherent property of the uPAR structure per se or whether it is induced upon ligand binding. The crystal structure of human uPAR in its ligand-free state would clarify this issue, but such information remains unfortunately elusive. We now report the crystal structures of a stabilized, human uPAR (H47C/N259C) in its ligand-free form to 2.4 Å and in complex with amino-terminal fragment (ATF) to 3.2 Å. The structure of uPAR(H47C/N259C) in complex with ATF resembles the wild-type uPAR·ATF complex, demonstrating that these mutations do not perturb the uPA binding properties of uPAR. The present structure of uPAR(H47C/N259C) provides the first structural definition of uPAR in its ligand-free form, which represents one of the biologically active conformations of uPAR as defined by extensive biochemical studies. The domain boundary between uPAR DI-DII domains is more flexible than the DII-DIII domain boundary. Two important structural features are highlighted by the present uPAR structure. First, the DI-DIII domain boundary may face the cell membrane. Second, loop 130-140 of uPAR plays a dynamic role during ligand loading/unloading. Together, these studies provide new insights into uPAR structure-function relationships, emphasizing the importance of the inter-domain dynamics of this modular receptor. PMID:22285761

  1. Acyclovir kinetics after intravenous infusion.

    PubMed

    de Miranda, P; Whitley, R J; Blum, M R; Keeney, R E; Barton, N; Cocchetto, D M; Good, S; Hemstreet, G P; Kirk, L E; Page, D A; Elion, G B

    1979-12-01

    The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.

  2. Arterial Catheterization

    MedlinePlus

    ... rial line can provide valuable information to adjust oxygen therapy or mechanical ventilator (respirator; breathing machine) settings. The blood oxygen pres- sure measures from an arterial line give ...

  3. Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor.

    PubMed

    Trimarchi, Hernán

    2013-11-01

    Primary focal and segmental glomerulosclerosis (FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.

  4. Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect.

    PubMed Central

    Resnati, M; Guttinger, M; Valcamonica, S; Sidenius, N; Blasi, F; Fazioli, F

    1996-01-01

    Physiological concentrations of urokinase plasminogen activator (uPA) stimulated a chemotactic response in human monocytic THP-1 through binding to the urokinase receptor (uPAR). The effect did not require the protease moiety of uPA, as stimulation was achieved also with the N-terminal fragment (ATF), while the 33 kDa low molecular weight uPA was ineffective. Co-immunoprecipitation experiments showed association of uPAR with intracellular kinase(s), as demonstrated by in vitro kinase assays. Use of specific antibodies identified p56/p59hck as a kinase associated with uPAR in THP-1 cell extracts. Upon addition of ATF, p56/p59hck activity was stimulated within 2 min and returned to normal after 30 min. Since uPAR lacks an intracellular domain capable of interacting with intracellular kinase, activation of p56/p59hck must require a transmembrane adaptor. Evidence for this was strongly supported by the finding that a soluble form of uPAR (suPAR) was capable of inducing chemotaxis not only in THP-1 cells but also in cells lacking endogenous uPAR (IC50, 5 pM). However, activity of suPAR require chymotrypsin cleavage between the N-terminal domain D1 and D2 + D3. Chymotrypsin-cleaved suPAR also induced activation of p56/p59hck in THP-1 cells, with a time course comparable with ATF. Our data show that uPA-induced signal transduction takes place via uPAR, involves activation of intracellular tyrosine kinase(s) and requires an as yet undefined adaptor capable of connecting the extracellular ligand binding uPAR to intracellular transducer(s). Images PMID:8612581

  5. Ligand Binding Alters Dimerization and Sequestering of Urokinase Receptors in Raft-Mimicking Lipid Mixtures

    PubMed Central

    Ge, Yifan; Siegel, Amanda P.; Jordan, Rainer; Naumann, Christoph A.

    2014-01-01

    Lipid heterogeneities, such as lipid rafts, are widely considered to be important for the sequestering of membrane proteins in plasma membranes, thereby influencing membrane protein functionality. However, the underlying mechanisms of such sequestration processes remain elusive, in part, due to the small size and often transient nature of these functional membrane heterogeneities in cellular membranes. To overcome these challenges, here we report the sequestration behavior of urokinase receptor (uPAR), a glycosylphosphatidylinositol-anchored protein, in a planar model membrane platform with raft-mimicking lipid mixtures of well-defined compositions using a powerful optical imaging platform consisting of confocal spectroscopy XY-scans, photon counting histogram, and fluorescence correlation spectroscopy analyses. This methodology provides parallel information about receptor sequestration, oligomerization state, and lateral mobility with single molecule sensitivity. Most notably, our experiments demonstrate that moderate changes in uPAR sequestration are not only associated with modifications in uPAR dimerization levels, but may also be linked to ligand-mediated allosteric changes of these membrane receptors. Our data show that these modifications in uPAR sequestration can be induced by exposure to specific ligands (urokinase plasminogen activator, vitronectin), but not via adjustment of the cholesterol level in the planar model membrane system. Good agreement of our key findings with published results on cell membranes confirms the validity of our model membrane approach. We hypothesize that the observed mechanism of receptor translocation in the presence of raft-mimicking lipid mixtures is also applicable to other glycosylphosphatidylinositol-anchored proteins. PMID:25418095

  6. Ligand binding alters dimerization and sequestering of urokinase receptors in raft-mimicking lipid mixtures.

    PubMed

    Ge, Yifan; Siegel, Amanda P; Jordan, Rainer; Naumann, Christoph A

    2014-11-01

    Lipid heterogeneities, such as lipid rafts, are widely considered to be important for the sequestering of membrane proteins in plasma membranes, thereby influencing membrane protein functionality. However, the underlying mechanisms of such sequestration processes remain elusive, in part, due to the small size and often transient nature of these functional membrane heterogeneities in cellular membranes. To overcome these challenges, here we report the sequestration behavior of urokinase receptor (uPAR), a glycosylphosphatidylinositol-anchored protein, in a planar model membrane platform with raft-mimicking lipid mixtures of well-defined compositions using a powerful optical imaging platform consisting of confocal spectroscopy XY-scans, photon counting histogram, and fluorescence correlation spectroscopy analyses. This methodology provides parallel information about receptor sequestration, oligomerization state, and lateral mobility with single molecule sensitivity. Most notably, our experiments demonstrate that moderate changes in uPAR sequestration are not only associated with modifications in uPAR dimerization levels, but may also be linked to ligand-mediated allosteric changes of these membrane receptors. Our data show that these modifications in uPAR sequestration can be induced by exposure to specific ligands (urokinase plasminogen activator, vitronectin), but not via adjustment of the cholesterol level in the planar model membrane system. Good agreement of our key findings with published results on cell membranes confirms the validity of our model membrane approach. We hypothesize that the observed mechanism of receptor translocation in the presence of raft-mimicking lipid mixtures is also applicable to other glycosylphosphatidylinositol-anchored proteins.

  7. Urokinase-Type Plasminogen Activator Promotes Dendritic Spine Recovery and Improves Neurological Outcome Following Ischemic Stroke

    PubMed Central

    Wu, Fang; Catano, Marcela; Echeverry, Ramiro; Torre, Enrique; Haile, Woldeab B.; An, Jie; Chen, Changhua; Cheng, Lihong; Nicholson, Andrew; Tong, Frank C.; Park, Jaekeun

    2014-01-01

    Spines are dendritic protrusions that receive most of the excitatory input in the brain. Early after the onset of cerebral ischemia dendritic spines in the peri-infarct cortex are replaced by areas of focal swelling, and their re-emergence from these varicosities is associated with neurological recovery after acute ischemic stroke (AIS). Urokinase-type plasminogen activator (uPA) is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor (uPAR). We report that cerebral cortical neurons release uPA during the recovery phase from ischemic stroke in vivo or hypoxia in vitro. Although uPA does not have an effect on ischemia- or hypoxia-induced neuronal death, genetic deficiency of uPA (uPA−/−) or uPAR (uPAR−/−) abrogates functional recovery after AIS. Treatment with recombinant uPA after ischemic stroke induces neurological recovery in wild-type and uPA−/− but not in uPAR−/− mice. Diffusion tensor imaging studies indicate that uPA−/− mice have increased water diffusivity and decreased anisotropy associated with impaired dendritic spine recovery and decreased length of distal neurites in the peri-infarct cortex. We found that the excitotoxic injury induces the clustering of uPAR in dendritic varicosities, and that the binding of uPA to uPAR promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from uPAR-enriched varicosities. This effect is independent of uPA's proteolytic properties and instead is mediated by Rac-regulated profilin expression and cofilin phosphorylation. Our data indicate that binding of uPA to uPAR promotes dendritic spine recovery and improves functional outcome following AIS. PMID:25339736

  8. Activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa.

    PubMed

    Beaufort, Nathalie; Seweryn, Paulina; de Bentzmann, Sophie; Tang, Aihua; Kellermann, Josef; Grebenchtchikov, Nicolai; Schmitt, Manfred; Sommerhoff, Christian P; Pidard, Dominique; Magdolen, Viktor

    2010-06-15

    Pathogenic bacteria, including Pseudomonas aeruginosa, interact with and engage the host plasminogen (Plg) activation system, which encompasses the urokinase (uPA)-type Plg activator, and is involved in extracellular proteolysis, including matrilysis and fibrinolysis. We hypothesized that secreted bacterial proteases might contribute to the activation of this major extracellular proteolytic system, thereby participating in bacterial dissemination. We report that LasB, a thermolysin-like metalloprotease secreted by Ps. aeruginosa, converts the human uPA zymogen into its active form (kcat=4.9 s-1, Km=8.9 microM). Accordingly, whereas the extracellular secretome from the LasB-expressing pseudomonal strain PAO1 efficiently activates pro-uPA, the secretome from the isogenic LasB-deficient strain PDO240 is markedly less potent in pro-uPA activation. Still, both secretomes induce some metalloprotease-independent activation of the human zymogen. The latter involves a serine protease, which we identified via both recombinant protein expression in Escherichia coli and purification from pseudomonal cultures as protease IV (PIV; kcat=0.73 s-1, Km=6.2 microM). In contrast, neither secretomes nor the pure proteases activate Plg. Along with this, LasB converts Plg into mini-Plg and angiostatin, whereas, as reported previously, it processes the uPA receptor, inactivates the plasminogen activator inhibitor 1, and activates pro-matrix metalloproteinase 2. PIV does not target these factors at all. To conclude, LasB and PIV, although belonging to different protease families and displaying quite different substrate specificities, both activate the urokinase-type precursor of the Plg activation cascade. Direct pro-uPA activation, as also reported for other bacterial proteases, might be a frequent phenomenon that contributes to bacterial virulence.

  9. Design of low cost smart infusion device

    NASA Astrophysics Data System (ADS)

    Saputra, Yohanes David; Purnamaningsih, Retno Wigajatri

    2015-01-01

    We propose design of a smart infusion device suitable for public hospitals in Indonesia. The device comprised of LED, photodiode and DC motor to measure and control the infusion rate, using the principle of LED beam absorption. The infusion rate was identified by using microcontroller and displayed through computer unit. Experiment results for different flow rate level and concentration of Dextrose showed that the device is able to detect, measure, and control the infusion droplets flow rate by the average error rate of 1.0081%.

  10. Effects of isoproterenol infusion on the hindlimb metabolism of growing wether lambs.

    PubMed

    Brown, J; Crompton, L A; Lomax, M A

    1991-01-01

    The effect of a mixed beta 1/beta 2-adrenergic agonist, isoproterenol, on hindlimb metabolism was studied in growing wether lambs using arteriovenous difference and blood flow rate techniques. Isoproterenol (48 micrograms kg-1 d-1), or saline, was infused into a jugular vein of five wether lambs (30 to 35 kg) for five days and samples taken on the fifth day of treatment. Infusion of isoproterenol significantly increased blood flow, oxygen uptake and tyrosine uptake across the hindlimb. Hindlimb non-esterified fatty acid uptake was increased but not significantly (P = 0.11) and arterial growth hormone concentration was not altered by isoproterenol infusion. Results suggest that beta-adrenergic agonists promote lean tissue deposition by increased muscle blood flow rate and amino acid uptake.

  11. Intra-arterial fibrinolytic treatment for mesenteric arterial embolus: a case report

    PubMed Central

    Kwauk, Sam T.M.; Bartlett, J. Henry; Hayes, Paul; Chow, Kenneth C.

    1996-01-01

    The diagnosis of mesenteric ischemia is based on acute clinical awareness of the condition and confirmed by angiography or laparotomy. The standard treatment is abdominal exploration with resection of the gangrenous segment of the bowel or embolectomy of the superior mesentery artery, or both. Alternative treatment such as intra-arterial thrombolysis may be considered in selected patients. A 66-year-old man with a history of atrial fibrillation presented with abdominal pain. Angiography documented an embolus in both the ileocolic artery and a branch of the right renal artery. The patient was treated with selective intra-arterial infusion of streptokinase. The abdominal pain resolved. Repeat angiography showed lysis of both emboli. PMID:8769930

  12. Renal electrolyte excretion and renin release during calcium and parathormone infusions in conscious rabbits.

    PubMed Central

    Peart, W S; Roddis, S A; Unwin, R J

    1986-01-01

    Following a random block experimental design in each case, three repeated measurement studies were carried out in three different groups of conscious rabbits, to investigate the renal effects of increasing doses of intravenous calcium chloride (CaCl2) and bovine parathyroid hormone (PTH). In the first study, each rabbit received either CaCl2 (0.15, 0.3, 0.5 or 1.0 mg kg-1 min-1) or vehicle alone (control) for 160 min. In the second study, rabbits were given either PTH (0.15 microgram kg-1 min-1), CaCl2 (1.0 mg kg-1 min-1), PTH plus CaCl2 (0.15 microgram kg-1 min-1 and 1.0 mg kg-1 min-1, respectively) or vehicle alone; PTH was infused for just over 60 min. In the third study, a much smaller dose (0.05 mg kg-1 min-1) of CaCl2 was infused for 100 min. CaCl2 infusion produced a striking fall in fractional excretion of sodium of at least 50% (P less than 0.01), but this was not dose related, being almost maximal at the smaller doses infused. Although this effect was evident in the absence of any changes in total plasma calcium concentration at the lower doses of CaCl2, renal calcium excretion was increased between 2- and 20-fold (P less than 0.01) at all doses infused. Fractional excretion of chloride doubled at the two higher doses of CaCl2 (P less than 0.01), but potassium excretion was unchanged. There were no consistent alterations in mean arterial blood pressure, effective renal plasma flow, glomerular filtration rate or plasma renin activity (PRA); total plasma calcium concentration was consistently elevated only during infusion of the high dose by just under 1 mmol l-1. PTH infusion had no measured effect on fractional excretion of sodium or renal calcium excretion, but doubled fractional potassium excretion (P less than 0.05). Heart rate and PRA increased (P less than 0.01 and less than 0.05, respectively), the latter by 50%, but systemic pressure and renal haemodynamics were not significantly affected. By contrast, PTH infused with CaCl2 produced a 4-fold rise

  13. Intraarterial Infusion Therapy via a Subcutaneous Port for Limb-Threatening Ischemia: A Pilot Study

    SciTech Connect

    Strecker, Ernst-Peter K.; Ostheim-Dzerowycz, Wladimir; Boos, Irene B.L.

    1998-03-15

    Purpose: To present the initial results of a new percutaneously implantable catheter port system (PIPS) used for long-term intraarterial infusion therapy in patients with severe ischemic limb disease. Methods: Ten patients with deep, extended ischemic ulcerations (all 10) and osteomyelitis (6/10) of the foot received intraarterial infusions of prostaglandine E{sub 1} and antibiotics, if indicated, via a new port catheter system with the port placed subcutaneously above the groin after percutaneous introduction and the catheter tip placed into the superficial or deep femoral artery. Results: Port implantation and repeated port access were uncomplicated. During the follow-up period (mean 11 months, range 1 week-50 months), port migration, leakage, or infection was not observed. Three catheters thrombosed and were opened by fibrinolysis with recombinant tissue plasminogen activator instilled via the port. Treatment success was achieved in 8 patients: relief from rest pain (8 patients), reduction of ulcer size (4/8), and complete healing (4/8). Limb savage rate was 80%. In 2 patients amputation could not be avoided. Conclusion: Selective long-term arterial infusion therapy presents a valuable therapeutic regimen for limb salvage. With the new catheter port system, repeated local intraarterial infusion is safe and simple.

  14. Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine.

    PubMed

    LeSage, Mark G; Keyler, Dan E; Shoeman, Don; Raphael, Donna; Collins, Gregory; Pentel, Paul R

    2002-05-01

    The effects of continuous nicotine infusion on nicotine self-administration (NSA) were studied in rats as a model of nicotine replacement therapy (NRT) in humans. A NSA model in which rats had 23-h/day access to nicotine was used to approximate nicotine access conditions in cigarette smokers. In order to estimate serum nicotine concentrations associated with NSA, arterial and venous serum nicotine concentrations were measured during a simulation of NSA. Nicotine was noncontingently administered as 30 doses/12 h of 0.03 mg/kg/i.n.f. or 60 doses/12 h of 0.01 mg/kg/i.n.f. daily. Venous serum nicotine concentrations were measured after the first nicotine dose of the day, and arterial and venous concentrations were measured after doses in the middle of the day. The range of mean concentrations measured was similar to those reported in cigarette smokers (venous concentrations 6-59 ng/ml, arterial concentrations 42-96 ng/ml). The effects of continuous nicotine infusion on NSA were studied by noncontingently administering nicotine at various rates via osmotic pump to animals self-administering nicotine (0.01 or 0.03 mg/kg/i.n.f.) during 23-h/day sessions. Continuous nicotine infusion at all infusion rates substantially suppressed NSA, but suppression was rate-related only for the 0.01-mg/kg/inf NSA unit dose. Nicotine infusion rates producing venous serum nicotine concentrations equaling or exceeding the peak venous levels associated with simulated NSA were more effective than lower infusion rates only at the lower NSA unit dose. The highest nicotine infusion rate had no sustained effect on food-maintained responding, demonstrating its specificity for suppression of NSA. These data provide a model for studying NRT in the rat.

  15. Mesenteric artery ischemia

    MedlinePlus

    ... bowel - mesenteric; Dead gut - mesenteric; Atherosclerosis - mesenteric artery; Hardening of the arteries - mesenteric artery ... the aorta, the main artery from the heart. Hardening of the arteries occurs when fat, cholesterol, and ...

  16. Infusing Systems Thinking into Career Counseling

    ERIC Educational Resources Information Center

    Ryan, Charles W.; Tomlin, James H.

    2010-01-01

    This study examined the role of career counselors in infusing systems thinking into occupational advising. The authors conducted a qualitative review and analysis of selected literature on systems thinking and analyzed trends for adaptation to career counseling practice. This analysis suggests that career counselors need to infuse systems…

  17. Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China

    PubMed Central

    Guo, Shui-Ming; Han, Min; Chen, Mei-Xue; Ning, Yong; Pei, Guang-Chang; Li, Yue-Qiang; Dai, Wei; Ge, Shu-Wang; Deng, Yuan-Jun; Guo, Yan-Yan; Li, Xiao-Qing; Haller, Hermann; Xu, Gang; Rong, Song

    2015-01-01

    Background Soluble urokinase receptor (suPAR) may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS) changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN). Methods We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed. Results We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001) and multivariate (P < 0.001) analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions. Conclusions Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN. PMID:26380984

  18. A comparative study of Sterofundin and Ringer lactate based infusion protocol in scoliosis correction surgery

    PubMed Central

    Sharma, Ashima; Yadav, Monu; Kumar, B. Rajesh; Lakshman, P. Sai; Iyenger, Raju; Ramchandran, Gopinath

    2016-01-01

    Background: A major change in anesthesia practice as regards to intraoperative infusion therapy is the present requirement. Switching over to balanced fluids can substantially decrease the incidence of lactic acidosis and hyperchloremic acidosis. The deleterious effects of unbalanced fluids are more recognizable during major surgeries. We prospectively studied the influence of Sterofundin (SF) and Ringer lactate (RL) on acid–base changes, hemodynamics, and readiness for extubation during scoliosis surgery. Subjects and Methods: Thirty consecutive children posted for scoliosis surgery were randomized to receive either RL (n = 15) or SF (n = 15) as intraoperative fluid at 10 mg/kg/h. Fluid boluses were added according to the study fluid algorithm. Arterial blood was sampled and analyzed at hourly intervals during surgery. Red blood cell transfusion was guided by hematocrit below 27. Patients were followed for 24 h postoperatively in the Intensive Care Unit. Results: There was no statistically significant difference in the volume of infused fluid (2400 ± 512 ml in Group RL and 2200 ± 640 ml in Group SF. There were no significant changes in pH of patients infused with SF. Statistically, significant higher lactate levels were seen in RL-infused group. The strong ion difference was decreased in both groups, but it normalized earlier with SF. Conclusions: SF-infused patients had nonremarkable changes in acid–base physiology in scoliosis surgery. PMID:27746547

  19. Recovery of urokinase from integrated mammalian cell culture cryogel bioreactor and purification of the enzyme using p-aminobenzamidine affinity chromatography.

    PubMed

    Bansal, Vibha; Roychoudhury, Pradip K; Mattiasson, Bo; Kumar, Ashok

    2006-01-01

    An integrated product recovery system was developed to separate urokinase from the cell culture broth of human kidney cells HT1080. Supermacroporous monolithic cryogels provided ideal matrices with respect to surface and flow properties for use as cell culture scaffold as well as for affinity chromatographic capture step of the enzyme in the integrated system. The urokinase was produced continuously in the reactor running for 4 weeks with continuous circulation of 500 ml of culture medium. The enzyme activity in the culture medium reached to 280 Plough units (PU)/mg protein. Cu(II)-iminodiacetic acid (IDA)-polyacrylamide (pAAm) cryogel column was used to capture urokinase by integrating with the gelatin-coupled pAAm-cryogel bioreactor for HT1080 cell culture. After removing the urokinase capture column from the integrated system the bound protein was eluted. The metal affinity capture step gave 4.5-fold purification of the enzyme thus achieving a specific activity of 1300 PU/mg protein. The enzyme eluate from Cu(II)-IDA-pAAm cryogel capture column was further purified on benzamidine-Sepharose affinity column. This step finally led to a homogeneous preparation of different forms of urokinase in two different elution peaks with a best urokinase activity of 13 550 PU/mg of protein. As compared to initial activity in the cell culture broth, about 26.2- and 48.4-fold increase in specific activity was achieved with enzyme yields corresponding to 32% and 35% in two different peak fractions, respectively. Native electrophoresis and SDS-PAGE showed multiple protein bands corresponding to different forms of the urokinase, which were confirmed by Western blotting and zymography. PMID:16761300

  20. Infant death due to air embolism from peripheral venous infusion.

    PubMed

    Sowell, Matthew W; Lovelady, Cari L; Brogdon, B G; Wecht, Cyril H

    2007-01-01

    An otherwise healthy male infant was brought to the hospital because the mother suspected superficial infection at the operative site 5 days after an inguinal hernia repair. He was admitted to the pediatric unit overnight to be evaluated by his surgeon the next morning. When a venous infusion of maintenance fluids was started, the patient immediately went into cardio-respiratory arrest and was pronounced dead after resuscitation efforts failed. Subsequently, air collections were found in both venous and arterial circulations, including the splenoportal system. Detailed review of the clinical presentation and course, laboratory results, radiological, and pathological findings, along with a review of pertinent literature provides an explanation for the death by air embolism. Apparent inconsistent findings both radiographically and at autopsy are resolved. The mechanism of distribution of air to both systemic and splenoportal circulation is discussed. We believe this to be only the eighth case reported in English-language literature of infantile death from peripheral venous infusion. In all age groups, we find only six other cases in the English-language literature of gas found concomitantly in both the systemic and portal venous systems. PMID:17209934

  1. [Treatment of arterial and venous brain ischemia. Experts' recommendations: stroke management in the intensive care unit].

    PubMed

    Calvet, D; Bracard, S; Mas, J-L

    2012-06-01

    With thrombolysis, intravenous alteplase (0.9 mg/kg body weight, maximum 90 mg), with 10% of the dose given as a bolus followed by a 60-minute infusion, is recommended within 4.5 hours of onset of ischemic stroke. When indicated, intravenous thrombolysis must be initiated as soon as possible. It is possible to use intravenous alteplase in patients with seizures at stroke onset, if the neurological deficit is related to acute cerebral ischemia. Intravenous alteplase can be discussed for use on a case-by-case basis, according to risk of bleeding, in selected patients under 18 years and over 80 years of age, although for the current European recommendations this would be an off-label use. In hospitals with a stroke unit, intravenous thrombolysis is prescribed by a neurologist (current French labelling) or a physician having the French certification for neurovascular diseases (outside the current French labelling). The patient must be monitored in the stroke unit or in case of multiple organ failure in an intensive and critical care unit. In hospitals without a stroke unit, thrombolysis must be decided by the neurologist from the corresponding stroke unit via telemedicine. It is recommended to perform brain imaging 24 hours after thromboysis. Intra-arterial thrombolysis can be contemplated on a case-by-case basis after multidisciplinary discussion within a 6-hour time window for patients with acute middle cerebral artery or carotid occlusions, and within a larger time window for patients with basilar artery occlusion, because of their very poor spontaneous prognosis. Mechanical thrombectomy can also be contemplated in the same situations. With antiplatelet agents, it is recommended that patients receive aspirin (160 mg-325 mg) within 48 hours of ischemic stroke onset. When thrombolysis is performed or contemplated, it is recommended to delay the initiation of aspirin or other antithrombotic drugs for 24 hours. The use of antiplatelet agents that inhibit the

  2. Arterial Stiffness

    PubMed Central

    Avolio, Alberto

    2013-01-01

    Stiffness of large arteries has been long recognized as a significant determinant of pulse pressure. However, it is only in recent decades, with the accumulation of longitudinal data from large and varied epidemiological studies of morbidity and mortality associated with cardiovascular disease, that it has emerged as an independent predictor of cardiovascular risk. This has generated substantial interest in investigations related to intrinsic causative and associated factors responsible for the alteration of mechanical properties of the arterial wall, with the aim to uncover specific pathways that could be interrogated to prevent or reverse arterial stiffening. Much has been written on the haemodynamic relevance of arterial stiffness in terms of the quantification of pulsatile relationships of blood pressure and flow in conduit arteries. Indeed, much of this early work regarded blood vessels as passive elastic conduits, with the endothelial layer considered as an inactive lining of the lumen and as an interface to flowing blood. However, recent advances in molecular biology and increased technological sophistication for the detection of low concentrations of biochemical compounds have elucidated the highly important regulatory role of the endothelial cell affecting vascular function. These techniques have enabled research into the interaction of the underlying passive mechanical properties of the arterial wall with the active cellular and molecular processes that regulate the local environment of the load-bearing components. This review addresses these emerging concepts. PMID:26587425

  3. Upper extremity arterial injury in athletes.

    PubMed

    McCarthy, W J; Yao, J S; Schafer, M F; Nuber, G; Flinn, W R; Blackburn, D; Suker, J R

    1989-02-01

    Between 1983 and 1986, 23 athletes were evaluated for arm and hand complaints. Eleven players had symptoms of thoracic outlet compression. Severe arm fatigue (eight patients) and finger ischemia (three patients) were the presenting symptoms. In the remaining 12 athletes, symptoms of hand ischemia were predominant. Noninvasive testing with Doppler ultrasonography and duplex scanning (positional testing and finger systolic pressure recording) and cold immersion were used to aid in diagnosis. In the 11 athletes with thoracic outlet compression, arteriography confirmed the finding with compression of the subclavian artery in five, the axillary artery in one, both subclavian and axillary arteries in two, posterior humeral circumflex artery in one, and subclavian aneurysm in two. Compression of the suprascapular artery was identified in four, the subscapular artery in two, and the posterior humeral circumflex artery in one. Thrombosis of a first baseman's ulnar artery and occlusion of the palmar arch in a frisbee player were documented by arteriography. Decompression of the thoracic outlet consisted of anterior scalenectomy in five, pectoralis minor muscle division in one, and resection of both muscles in two. Removal of cervical rib with interposed vein graft was performed in the two players with arterial aneurysm. Hand ischemia in the remaining athletes was treated conservatively with Dextran-heparin infusion for acute ischemia. Repeat noninvasive study of all players demonstrated absence of compression in their playing position, and all have resumed their playing careers. Hand ischemia in athletes can be evaluated noninvasively and treated conservatively. Resection of hypertrophied muscles to decompress the thoracic outlet together with release of branch artery compression in selected athletes promotes perfusion to arm and shoulder muscles and helps to avoid the catastrophic complication of repetitive trauma leading to sudden arterial thrombosis.

  4. Safety of rapid intravenous of infusion acetaminophen

    PubMed Central

    2013-01-01

    Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I–III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications. PMID:23814378

  5. Safety of rapid intravenous of infusion acetaminophen.

    PubMed

    Needleman, Steven M

    2013-07-01

    Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I-III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications. PMID:23814378

  6. Financial analysis for the infusion alliance.

    PubMed

    Perucca, Roxanne

    2010-01-01

    Providing high-quality, cost-efficient care is a major strategic initiative of every health care organization. Today's health care environment is transparent; very competitive; and focused upon providing exceptional service, safety, and quality. Establishing an infusion alliance facilitates the achievement of organizational strategic initiatives, that is, increases patient throughput, decreases length of stay, prevents the occurrence of infusion-related complications, enhances customer satisfaction, and provides greater cost-efficiency. This article will discuss how to develop a financial analysis that promotes value and enhances the financial outcomes of an infusion alliance. PMID:20841984

  7. Pancreatic enzyme secretion during intravenous fat infusion.

    PubMed

    Burns, G P; Stein, T A

    1987-01-01

    The nutritional support of patients with pancreatic and high gastrointestinal fistulas and severe pancreatitis frequently involves intravenous fat infusion. There are conflicting reports on the effect of intravenous fat on pancreatic exocrine secretion. In 10 dogs with chronic pancreatic fistulas, pancreatic juice was collected during secretin (n = 10) or secretin + cholecystokinin (n = 4) stimulation, with and without intravenous fat infusion (5 g/hr). The hormonal-stimulated secretion of lipase, amylase, trypsin, total protein, bicarbonate, and water was unchanged during fat infusion. This study supports the use of intravenous fat as a nutritional source when it is desirable to avoid stimulation of the pancreas.

  8. Visualizing enzyme infusion into apple tissue.

    PubMed

    Culver, C A; Bjurlin, M A; Fulcher, R G

    2000-12-01

    Enzymes traditionally used in food processing are applied to ground or macerated tissue with little or no retention of cellular structure. More recently developed applications use enzymes to selectively alter tissue properties while retaining some structure. Process development has been hindered by the lack of conclusive evidence showing that enzyme infusion into plant tissue pieces is possible. This study provides direct evidence that such infusion is possible by using fluorescence microscopy to monitor vacuum infusion of fluorescein-labeled alpha-amylase into apple cubes. This method is generally applicable to any plant or animal tissue and to any macromolecule capable of derivatization. PMID:11141264

  9. Space Tethers Programmatic Infusion Opportunities

    NASA Technical Reports Server (NTRS)

    Bonometti, J. A.; Frame, K. L.

    2005-01-01

    Programmatic opportunities abound for space Cables, Stringers and Tethers, justified by the tremendous performance advantages that these technologies offer and the rather wide gaps that must be filled by the NASA Exploration program, if the "sustainability goal" is to be met. A definition and characterization of the three categories are presented along with examples. A logical review of exploration requirements shows how each class can be infused throughout the program, from small experimental efforts to large system deployments. The economics of tethers in transportation is considered along with the impact of stringers for structural members. There is an array of synergistic methodologies that interlace their fabrication, implementation and operations. Cables, stringers and tethers can enhance a wide range of other space systems and technologies, including power storage, formation flying, instrumentation, docking mechanisms and long-life space components. The existing tether (i.e., MXER) program's accomplishments are considered consistent with NASA's new vision and can readily conform to requirements-driven technology development.

  10. Carotid artery surgery

    MedlinePlus

    Carotid endarterectomy; CAS surgery; Carotid artery stenosis - surgery; Endarterectomy - carotid artery ... through the catheter around the blocked area during surgery. Your carotid artery is opened. The surgeon removes ...

  11. Percutaneous treatment of intrabdominal abscess: urokinase versus saline serum in 100 cases using two surgical scoring systems in a randomized trial.

    PubMed

    Laborda, A; De Gregorio, M A; Miguelena, J M; Medrano, J; Gómez-Arrue, J; Serrano, C; de Blas, I; Gimenez, M; D'Agostino, H

    2009-07-01

    The purpose of this study was to assess whether regular instillation of urokinase during abscess drainage leads to an improved outcome compared to saline irrigation alone. One hundred patients referred for image-guided abdominal abscess drainage were randomized between thrice daily urokinase instillation or saline irrigation alone. At the end of the study, patient medical records were reviewed to determine drainage, study group, Altona (PIA II) and Mannheim (MPI) scoring, duration of drainage, procedure-related complications, hospital stay duration, and clinical outcome. The technical success rate of the percutaneous abscess drainage was 100%. The success or failure of abscess remission did not differ significantly between groups (success rate of 91.5% in the urokinase group vs. 88.8% in the saline group; failure rate was of 8.5 vs. 21.2%, respectively); however, days of drainage, main hospital stay, and overall costs were significantly reduced in patients treated with urokinase compared to the control group (P < 0.05). No adverse effects from urokinase were observed. Surgical scores were a useful homogeneity factor, and MPI showed a good correlation with prognosis, while PIA results did not have a significant correlation. For drainage of complex abscesses (loculations, hemorrhage, viscous material), fibrinolytics safely accelerate drainage and recovery, reducing the length of the hospital stay and, therefore, the total cost. PMID:19190912

  12. Feeding in sheep during intraportal infusions of short-chain fatty acids and the effect of liver denervation

    PubMed Central

    Anil, M. H.; Forbes, J. M.

    1980-01-01

    1. Castrated male sheep were prepared with cannulae in the hepatic portal vein and jugular vein through which infusions lasting for 3 hr were made. Animals had free access to a pelleted feed the weight of which was continuously recorded so that feeding behaviour could be studied. 2. Infusion into the portal vein of a mixture of salts of short-chain fatty acids (acetate, propionate, butyrate: 55, 30, 15) caused a dose-dependent depression in food intake, feeding stopping completely with 4·0 m-mole/min of the mixture. Jugular infusion depressed intake slightly, compared with controls. 3. Separate infusions of salts of the three acids showed that the effect of the mixture was due almost entirely to its propionate content; 1·2 m-mole/min of propionate into the portal vein almost completely prevented feeding (39 g eaten per 3 hr) compared with jugular infusion at the same rate (210 g) or no infusion (205 g). 4. Surgical sectioning of the hepatic nerve plexus around the wall of the hepatic artery was attempted. Of seven animals which recovered normal food intake, three continued to eat during portal vein infusions of propionate at 1·2 m-mole/min; these sheep were subsequently shown to have been at least 95% denervated. One animal was 50% denervated and ate normally during some infusions but not others. In the remaining three, feeding was suppressed by portal vein infusion of propionate, and these were less than 75% denervated. 5. It was concluded that there are receptors in the liver which are sensitive to propionate and which have afferent fibres in the hepatic plexus. ImagesPlate 1 (cont.)Plate 1 PMID:7359422

  13. Ultrastructural localization of plasma membrane-associated urokinase- type plasminogen activator at focal contacts

    PubMed Central

    1988-01-01

    We have recently shown that urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 are both found extracellularly beneath cultured human skin fibroblasts and HT-1080 sarcoma cells, but in distinct localizations. Here, the ultrastructural distribution of u-PA was studied using immunoferritin electron microscopy. In HT-1080 cells, u-PA on the extracellular aspect of the plasma membrane was detected at sites of direct contact of the cell with the growth substratum beneath all parts of the ventral cell surface. The ferritin-labeled adhesion plaques, which were enriched in submembraneous microfilaments, were frequently seen at the leading lamellae of the cells as well as in lamellipodia and microspikes. Besides the cell-substratum adhesion plaques, ferritin label was detected at cell-cell contact sites. Double-label immunofluorescence showed a striking colocalization of u-PA and vinculin in both HT-1080 cells and WI-38 lung fibroblasts, which is consistent with u-PA being a focal contact component. The u-PA-containing focal contacts of WI-38 cells had no direct codistribution with fibronectin fibrils. In WI-38 cells made stationary by cultivation in a medium containing 0.5% FCS, vinculin plaques became highly elongated and more centrally located, whereas u-PA immunolabel disappeared from such focal adhesions. These findings show that plasma membrane-associated u-PA is an intrinsic component of focal contacts, where, we propose, it enables directional proteolysis for cell migration and invasion. PMID:3123496

  14. [Preparation of novel magnetic dextran affinity adsorbents and their application to purify urokinase].

    PubMed

    Dong, Y S; Liang, F; Yu, X Y; Guo, L A; Chang, J H

    2001-01-01

    The reverse phase suspension and embedment technique were adopted to prepare magnetic dextran microsphere (MDMS). The dispersion medium was mixture of some organic solvents. Span-80 was used as stabilizer. The aqueous dextran with magnetic fluid was suspended in dispersion medium with epichlorohydrin as cross-linking reagent. The mixture was stirred for 30 minutes at room temperature and then heated at 70 degrees C for 4 hours, MDMS was thus obtained. MDMS was activated by epichlorohydrin on which 6-aminohexanoic acid, glycine or ethylene diamine was bonded as spacers. Then it was coupled with p-aminobenzamide, L-arginine methyl ester or guanidohexanoic acid and five magnetic affinity adsorbents were prepared. The MDMS was polydisperse particles with the size of 50-300 meshes and the content of Fe3O4 was about 6.2 per cent in the MDMS. Influence of some parameters such as viscosity and density of organic phase, the volume ratio of organic and aqueous phase, the quantity of surfactant and stirring speed on preparing MDMS was studied. Magnetic affinity adsorbents were used to purify crude urokinase in a bath mode and the effect of coupling reagents and ligands on results of purification was discussed. The bioactivity recovery was 40.0 to 60.7 per cent, the purification-fold was between 14.9 and 32.8, and the adsorptive capacity varies from 89 mg to 121 mg per milliliter of adsorbent. PMID:12541840

  15. Relationship between cathepsin D, urokinase, and plasminogen activator inhibitors in malignant vs benign breast tumours.

    PubMed Central

    Foucré, D.; Bouchet, C.; Hacène, K.; Pourreau-Schneider, N.; Gentile, A.; Martin, P. M.; Desplaces, A.; Oglobine, J.

    1991-01-01

    The concentrations of cathepsin D (Cath D), urokinase (uPA) and two plasminogen activator inhibitors (PAI-1 and PAI-2) were analysed in the cytosols of 130 human mammary tumours (43 benign tumours and 87 primary and unilateral breast carcinomas). uPA, PAI-1 and PAI-2 levels were measured by antigenic immunoassays and Cath D by immunoradiometric assay. The median levels of the four parameters were significantly higher in the malignant tumours than in the benign ones. Cath D and uPA increases were 4-fold and 5-fold respectively. PAI-1 and PAI-2 increases were much more important, 74-fold and 29-fold respectively. In malignant tumours, median levels of Cath D and uPA did not vary according to classical prognostic factors (histologic grade, presence or absence of axillary lymph nodes, steroid receptors, UICC stage, tumour size, age, and menopausal status). However, PAI-1 decreased in ER+ and PR+ tumours and PAI-2 increased in menopausal women's tumours. When Cath D, uPA, PAI-1 and PAI-2 levels in malignant tumours were compared, positive correlations were found for all combinations. The implication of plasminogen activator inhibitors in the phenomenon was surprising and merits further investigation using tools other than global antigen measurements in tumours. PMID:1931618

  16. Differential expression of the urokinase receptor (CD87) in arthritic and normal synovial tissues.

    PubMed Central

    Szekanecz, Z; Haines, G K; Koch, A E

    1997-01-01

    AIM: To determine whether the urokinase plasminogen activator receptor (u-PAR; CD87) exhibits a possible pathogenic role in rheumatoid and osteoarthritis. METHODS: A semiquantitative, indirect immunoperoxidase histochemical analysis was performed on frozen synovial tissue sections. The recently characterised monoclonal antibody 10G7 recognising transfectants bearing u-PAR was used. Synovial tissue was obtained from 10 patients with rheumatoid arthritis, 10 patients with osteoarthritis, and four normal subjects. RESULTS: u-PAR was expressed on 70-90% of synovial tissue lining cells and subsynovial, interstitial macrophages from the arthritis patients, but only on a few myeloid cells from the normal subjects. It was also present on more endothelial cells from the rheumatoid and osteoarthritis patients, than from normal synovial tissue. CONCLUSIONS: Plasminogen activators are important in joint destruction underlying arthritis. The up-regulated expression of u-PAR in diseased versus normal synovial tissue suggests a role for this antigen in the inflammatory and angiogenic mechanisms underlying rheumatoid and osteoarthritis. Images PMID:9215148

  17. Electroanalysis of pM-levels of urokinase plasminogen activator in serum by phosphorothioated RNA aptamer.

    PubMed

    Jarczewska, Marta; Kékedy-Nagy, László; Nielsen, Jesper S; Campos, Rui; Kjems, Jørgen; Malinowska, Elżbieta; Ferapontova, Elena E

    2015-06-01

    Protein biomarkers of cancer allow a dramatic improvement in cancer diagnostics as compared to the traditional histological characterisation of tumours by enabling a non-invasive analysis of cancer development and treatment. Here, an electrochemical label-free assay for urokinase plasminogen activator (uPA), a universal biomarker of several cancers, has been developed based on the recently selected uPA-specific fluorinated RNA aptamer, tethered to a gold electrode via a phosphorothioated dA tag, and soluble redox indicators. The binding properties of the uPA-aptamer couple and interference from the non-specific adsorption of bovine serum albumin (BSA) were modulated by the electrode surface charge. A nM uPA electroanalysis at positively charged surfaces, complicated by the competitive adsorption of BSA, was tuned to the pM uPA analysis at negative surface charges of the electrode, being improved in the presence of negatively charged BSA. The aptamer affinity for uPA displayed via the binding/dissociation constant relationship correspondingly increased, ca. three orders of magnitude, from 0.441 to 367. Under optimal conditions, the aptasensor allowed 10(-12)-10(-9) M uPA analysis, also in serum, being practically useful for clinical applications. The proposed strategy for optimization of the electrochemical protein sensing is of particular importance for the assessment and optimization of in vivo protein ligand binding by surface-tethered aptamers.

  18. Expression of MMP-2, MMP-9, and urokinase-type plasminogen activator in cervical intraepithelial neoplasia.

    PubMed

    No, Jae Hong; Jo, Hoenil; Kim, Su-Hyeong; Park, In-Ae; Kang, Daehee; Lee, Chae Hyeong; Han, Seung-Su; Kim, Jae Weon; Park, Noh-Hyun; Kang, Soon-Beom; Song, Yong-Sang

    2009-08-01

    Matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator (uPA) are important factors for cancer invasion and metastasis, degrading the extracellular matrix. They are also associated with angiogenesis. Angiogenic phenotype is another feature of high-grade cervical intraepithelial neoplasia (CIN). However, their associations with the progression of low-grade CIN to high-grade CIN are unexplored. We investigated whether these proteolytic enzyme expressions correlate with the progression of CIN. A total of 39 paraffin-embedded specimens from 10 patients with CIN grade 1, nine with CIN grade 2, and 20 with CIN grade 3 were assessed immunohistochemically by specific antibodies against MMP-2, MMP-9, and uPA. MMP-9 expression was higher in CIN 3 lesions (47.4%) than in CIN 1 (22.2%) and CIN 2 (20.2%) lesions, although the difference failed to reach statistical significance. The expression level of uPA and MMP-2 was not associated with the grade of CIN lesions. Interestingly, we found a significant association between expressions of uPA and MMP-2 (P= 0.028). Our results suggest that MMP-9 might play a role in the progression of CIN.

  19. Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.

    PubMed

    Bao, Ying-Na; Cao, Xue; Luo, Dong-Hua; Sun, Rui; Peng, Li-Xia; Wang, Lin; Yan, Yong-Pan; Zheng, Li-Sheng; Xie, Ping; Cao, Yun; Liang, Ying-Ying; Zheng, Fang-Jing; Huang, Bi-Jun; Xiang, Yan-Qun; Lv, Xing; Chen, Qiu-Yan; Chen, Ming-Yuan; Huang, Pei-Yu; Guo, Ling; Mai, Hai-Qiang; Guo, Xiang; Zeng, Yi-Xin; Qian, Chao-Nan

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target. PMID:24763226

  20. A Urokinase Receptor-Bim Signaling Axis Emerges During EGFR Inhibitor Resistance in Mutant EGFR Glioblastoma

    PubMed Central

    Wykosky, Jill; Hu, Jingjing; Gomez, German G.; Taylor, Tiffany; Villa, Genaro R.; Pizzo, Donald; VandenBerg, Scott R.; Thorne, Amy Haseley; Chen, Clark C.; Mischel, Paul S.; Gonias, Steven. L.; Cavenee, Webster K.; Furnari, Frank B.

    2014-01-01

    EGFR is the most common genetically altered oncogene in glioblastoma (GBM), but small molecule EGFR tyrosine kinase inhibitors (TKIs) have failed to yield durable clinical benefit. Here we show that in two novel model systems of acquired resistance to EGFR TKIs, elevated expression of urokinase plasminogen activator (uPA) drives signaling through the MAPK pathway, which results in suppression of the pro-apoptotic BCL2-family member protein BIM (BCL2L11). In patient-derived GBM cells and genetic GBM models uPA is shown to suppress BIM levels through ERK1/2 phosphorylation, which can be reversed by siRNA mediated knockdown of uPA. TKI-resistant GBMs are re-sensitized to EGFR TKIs by pharmacological inhibition of MEK or a BH3 mimetic drug to replace BIM function. A link between the uPA-uPAR-ERK1/2 pathway and BIM has not been previously demonstrated in GBM, and involvement of this signaling axis in resistance provides rationale for a new strategy to target EGFR TKI-resistant GBM. PMID:25432173

  1. Modulation of urokinase plasminogen activator system by poly(ADP-ribose)polymerase-1 inhibition.

    PubMed

    Madunić, Josip; Antica, Mariastefania; Cvjetko, Petra; Požgaj, Lidija; Matulić, Maja

    2016-08-01

    The urokinase plasminogen activator (uPA) system is a complex regulator of extracellular proteolysis which is involved in various physiological and pathological processes. The major components of this system are the serine protease uPA, two inhibitors PAI-1 and PAI-2, and the receptor uPAR. It has been previously shown by several groups that the uPA system has an important role in cancer progression and therefore its possible prognostic and therapeutic value has been evaluated. The aim of this study is to tackle the role of poly(ADP-ribosyl)ation in the induction of uPA activity in a glioblastoma cell line, A1235. This cell line is sensitive to alkylation damage and is a model for drug treatment. The components of the uPA system and the level of DNA damage were analyzed after alkylation agent treatment in combination with poly(ADP-ribose)polymerase-1 (PARP-1) inhibition. Here we show that the increase in uPA activity results from the net balance change between uPA and its inhibitor at mRNA level. Further, PARP-1 inhibition exerts its influence on uPA activity through DNA damage increase. Involvement of several signaling pathways, as well as cell specific regulation influencing the uPA system are discussed.

  2. Augmented expression of urokinase plasminogen activator and extracellular matrix proteins associates with multiple myeloma progression.

    PubMed

    Khan, Rehan; Gupta, Nidhi; Kumar, Raman; Sharma, Manoj; Kumar, Lalit; Sharma, Alpana

    2014-06-01

    Multiple myeloma (MM) represents a B cell malignancy, characterized by a monoclonal proliferation of malignant plasma cells. Interactions between tumor cells and extracellular matrix (ECM) are of importance for tumor invasion and metastasis. Protein levels of urokinase plasminogen activator (uPA) and fibulin 1, nidogen and laminin in plasma and serum respectively and mRNA levels of these molecules in peripheral blood mononuclear cells were determined in 80 subjects by using ELISA and quantitative PCR and data was analyzed with severity of disease. Pearson correlation was determined to observe interrelationship between different molecules. A statistical significant increase for ECM proteins (laminin, nidogen and fibulin 1) and uPA at circulatory level as well as at mRNA level was observed compared to healthy controls. The levels of these molecules in serum might be utilized as a marker of active disease. Significant positive correlation of all ECM proteins with uPA was found and data also correlates with severity of disease. Strong association found between ECM proteins and uPA in this study supports that there might be interplay between these molecules which can be targeted. This study on these molecules may help to gain insight into processes of growth, spread, and clinical behavior of MM.

  3. Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

    PubMed Central

    Saleem, Moin A.; Meijers, Björn

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels. PMID:27504461

  4. TFRC and ACTB as the best reference genes to quantify Urokinase Plasminogen Activator in breast cancer

    PubMed Central

    2011-01-01

    Background Biomedical researchers have long looked for ways to diagnose and treat cancer patients at the early stages through biomarkers. Although conventional techniques are routinely applied in the detection of biomarkers, attitudes towards using Real-Time PCR techniques in detection of many biomarkers are increasing. Normalization of quantitative Real-Time PCR is necessary to validate non-biological alteration occurring during the steps of RNA quantification. Selection of variably expressed housekeeping genes (HKs) will affect the validity of the data. The aim of the present study was to identify uniformly expressed housekeeping genes in order to use in the breast cancer gene expression studies. Urokinase Plasminogen Activator was used as a gene of interest. Findings The expression of six HKs (TFRC, GUSB, GAPDH, ACTB, HPRT1 and RPLP0) was investigated using geNorm and NormFinder softwares in forty breast tumor, four normal and eight adjacent tissues. RPLP0 and GAPDH revealed maximum M value, while TFRC demonstrated lowest M value. Conclusions In the present study the most and the least stable genes were TFRC and RPLP0 respectively. TFRC and ACTB were verified as the best combination of two genes for breast cancer quantification. The result of this study shows that in each gene expression analysis HKs selection should be done based on experiment conditions. PMID:21702980

  5. Urokinase plasminogen activator receptor-deficient mice demonstrate reduced hyperoxia-induced lung injury.

    PubMed

    van Zoelen, Marieke A D; Florquin, Sandrine; de Beer, Regina; Pater, Jennie M; Verstege, Marleen I; Meijers, Joost C M; van der Poll, Tom

    2009-06-01

    Patients with respiratory failure often require supplemental oxygen therapy and mechanical ventilation. Although both supportive measures are necessary to guarantee adequate oxygen uptake, they can also cause or worsen lung inflammation and injury. Hyperoxia-induced lung injury is characterized by neutrophil infiltration into the lungs. The urokinase plasminogen activator receptor (uPAR) has been deemed important for leukocyte trafficking. To determine the expression and function of neutrophil uPAR during hyperoxia-induced lung injury, uPAR expression was determined on pulmonary neutrophils of mice exposed to hyperoxia. Hyperoxia exposure (O2>80%) for 4 days elicited a pulmonary inflammatory response as reflected by a profound rise in the number of neutrophils that were recovered from bronchoalveolar lavage fluid and lung cell suspensions, as well as increased bronchoalveolar keratinocyte-derived chemokine, interleukin-6, total protein, and alkaline phosphatase levels. In addition, hyperoxia induced the migration of uPAR-positive granulocytes into lungs from wild-type mice compared with healthy control mice (exposed to room air). uPAR deficiency was associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, which was accompanied by a strong reduction in lung injury. Furthermore, in uPAR(-/-) mice, activation of coagulation was diminished. These data suggest that uPAR plays a detrimental role in hyperoxia-induced lung injury and that uPAR deficiency is associated with diminished neutrophil influx into both lung tissues and bronchoalveolar spaces, accompanied by decreased pulmonary injury. PMID:19435793

  6. Loss of Urokinase Receptor Sensitizes Cells to DNA Damage and Delays DNA Repair

    PubMed Central

    Narayanaswamy, Pavan B.; Hodjat, Mahshid; Haller, Hermann; Dumler, Inna; Kiyan, Yulia

    2014-01-01

    DNA damage induced by numerous exogenous or endogenous factors may have irreversible consequences on the cell leading to cell cycle arrest, senescence and cell death. The DNA damage response (DDR) is powerful signaling machinery triggered in response to DNA damage, to provide DNA damage recognition, signaling and repair. Most anticancer drugs induce DNA damage, and DNA repair in turn attenuates therapeutic efficiency of those drugs. Approaches delaying DNA repair are often used to increase efficiency of treatment. Recent data show that ubiquitin-proteasome system is essential for signaling and repair of DNA damage. However, mechanisms providing regulation of proteasome intracellular localization, activity, and recruitment to DNA damage sites are elusive. Even less investigated are the roles of extranuclear signaling proteins in these processes. In this study, we report the involvement of the serine protease urokinase-type plasminogen activator receptor (uPAR) in DDR-associated regulation of proteasome. We show that in vascular smooth muscle cells (VSMC) uPAR activates DNA single strand break repair signaling pathway. We provide evidence that uPAR is essential for functional assembly of the 26S proteasome. We further demonstrate that uPAR mediates DNA damage-induced phosphorylation, nuclear import, and recruitment of the regulatory subunit PSMD6 to proteasome. We found that deficiency of uPAR and PSMD6 delays DNA repair and leads to decreased cell survival. These data may offer new therapeutic approaches for diseases such as cancer, cardiovascular and neurodegenerative disorders. PMID:24987841

  7. Challenges for drug discovery - a case study of urokinase receptor inhibition

    PubMed Central

    Chen, Zhuo; Lin, Lin; Huai, Qing; Huang, Mingdong

    2009-01-01

    Urokinase receptor (uPAR) is a widely recognized target for potential treatment of cancer. The development of uPAR inhibitors has been going on for over a decade. Despite the identification and validation of many highly potent hits using screening or medicinal approaches, none of them has been moved further along the drug discovery pipeline. The development of uPAR inhibitors exemplifies several challenges now faced by drug discovery. These include 1) hydrophobicity and thus poor bioavailability of the inhibitors from screening approaches; 2) specificity of the inhibitor, where a peptidyl inhibitor causes conformational change of the receptor; 3) species specificity, where some inhibitors developed based on the human receptor do not inhibit the murine receptor and thus cannot be validated in mouse models. The recently determined crystal structures of uPAR in complex with its ligand or inhibitor not only provide the structural insight to understand these challenges but also offer a potential solution for further inhibitor development and thus illustrate the importance of structural information in facilitating drug discovery. PMID:20025562

  8. Mycophenolate mofetil alleviates lupus nephritis through urokinase receptor signaling in a mice model.

    PubMed

    Cheng, C-C; Lee, Y-F; Lan, J-L; Wu, M-J; Hsieh, T-Y; Lin, N-N; Wang, J-M; Chiu, Y-T

    2013-05-01

    Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics. PMID:23478030

  9. Mycophenolate mofetil alleviates lupus nephritis through urokinase receptor signaling in a mice model.

    PubMed

    Cheng, C-C; Lee, Y-F; Lan, J-L; Wu, M-J; Hsieh, T-Y; Lin, N-N; Wang, J-M; Chiu, Y-T

    2013-05-01

    Lupus nephritis (LN) is usually associated with widespread effacement of the podocytes' foot processes leading to proteinuria. Induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via promoting podocytes' motility and kidney permeability in the glomerulus. Very little is known about uPAR signaling in LN. Mycophenolate mofetil (MMF), an immunosuppressive agent, efficiently modulates the development of LN in humans and mice, but there are no data concerning the direct uPAR involvement on podocytes in LN. The MMF efficiency and uPAR involvement signaling in NZB×NZW F1 lupus-prone mice were examined by proteinuria, renal function and pathology, immune complex deposits, and uPAR expression of podocytes by immunofluorescence staining and quantitative RT-PCR. After MMF treatment, the proteinuria (p < 0.01), BUN level (p < 0.05) and immunodeposition in glomeruli (p < 0.001) were significantly improved. Most important, the renal uPAR mRNA levels (p < 0.001) and uPAR protein level of podocytes (p < 0.001) were significantly reduced. The beneficial effect of MMF on LN could be attributed, at least in part, to the inhibition of uPAR expression in podocytes. These findings demonstrated uPAR could have potential as a predictive index for response to LN therapeutics.

  10. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

    SciTech Connect

    Patecki, Margret; Schaewen, Markus von; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika . E-mail: angelika.kusch@charite.de

    2007-08-03

    The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury.

  11. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

    PubMed Central

    Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

    2014-01-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

  12. The steady states and dynamics of urokinase-mediated plasmin activation.

    PubMed

    Venkatraman, Lakshmi; Yu, Hanry; Bhowmick, Sourav S; Dewey, Forbes; Tucker-Kellogg, Lisa

    2010-01-01

    Plasmin and urokinase-type plasminogen activator (uPA) are ubiquitous proteases regulating the extracellular environment. They can activate each other via proteolytic cleavage, suggesting the potential for complex dynamic behaviors that could be elucidated by computational modeling. Ordinary differential equations are constructed to model the activation dynamics of plasminogen into plasmin, and single-chain uPA (scUPA) into two-chain uPA (tcUPA). Computational simulations and phase plane analysis reveal two stable steady states for the activation of each protein. Bifurcation analysis shows the in silico system to be bistable. Cell-free experiments verify the system to have ultrasensitive activation behavior, where scUPA is the stimulus and plasmin the output. Furthermore, two significantly different steady states could be seen in vitro for the same stimulus levels, depending on the initial activation level of the plasmin. The switch-like dynamics of the uPA-plasmin system could have potential relevance to many normal and disease processes including angiogenesis, migration and metastasis, wound healing and fibrosis. PMID:19908371

  13. Involvement of urokinase-type plasminogen activator system in cancer: an overview.

    PubMed

    Mekkawy, Ahmed H; Pourgholami, Mohammad H; Morris, David L

    2014-09-01

    Currently, there are several studies supporting the role of urokinase-type plasminogen activator (uPA) system in cancer. The association of uPA to its receptor triggers the conversion of plasminogen into plasmin. This process is regulated by the uPA inhibitors (PAI-1 and PAI-2). Plasmin promotes degradation of basement membrane and extracellular matrix (ECM) components as well as activation of ECM latent matrix metalloproteases. Degradation and remodeling of the surrounding tissues is crucial in the early steps of tumor progression by facilitating expansion of the tumor mass, release of tumor growth factors, activation of cytokines as well as induction of tumor cell proliferation, migration, and invasion. Hence, many tumors showed a correlation between uPA system component levels and tumor aggressiveness and survival. Therefore, this review summarizes the structure of the uPA system, its contribution to cancer progression, and the clinical relevance of uPA family members in cancer diagnosis. In addition, the review evaluates the significance of uPA system in the development of cancer-targeted therapies.

  14. Acute Ischemic Stroke Involving Both Anterior and Posterior Circulation Treated by Endovascular Revascularization for Acute Basilar Artery Occlusion via Persistent Primitive Trigeminal Artery

    PubMed Central

    Fujita, Atsushi; Hosoda, Kohkichi; Kohmura, Eiji

    2016-01-01

    We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke. PMID:27446523

  15. The History of Target-Controlled Infusion.

    PubMed

    Struys, Michel M R F; De Smet, Tom; Glen, John Iain B; Vereecke, Hugo E M; Absalom, Anthony R; Schnider, Thomas W

    2016-01-01

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted ("target") drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical and regulatory issues addressed in prototype development. We also describe the launch of the current clinically available systems.

  16. Fiberoptic observation of thrombosis and thrombolysis in isolated human coronary arteries.

    PubMed

    Uchida, Y; Masuo, M; Tomaru, T; Kato, A; Sugimoto, T

    1986-10-01

    Coronary arteries isolated from cadavers autopsied within 7 hours after death were perfused with canine arterial blood, and the processes of thrombus formation at the segments stenosed with atheroma and the thrombolytic effects of urokinase were investigated by angioscopy. Ten minutes of blood perfusion caused thin mural thrombi localized at the stenotic or nonstenotic segments. During 30 minutes of blood perfusion, the thin mural thrombi of the outlet or inlet of the segment grew into a doughnut-shaped thrombus. Also, the thin mural thrombi in the stenotic segment grew into a streamer-like thrombus and drifted downstream. These thrombi grew in size with increasing perfusion time and finally obstructed the stenotic segment. Globular thrombi close to the outlet also were formed in a few preparations. Unlike the thrombi at the stenotic segment, the mural thrombi in the nonstenotic segments did not grow into massive thrombi. The thrombi were reduced in size within 10 minutes of perfusion with 320 U/ml or more of urokinase. During thrombolysis, sandstorm-like dispersion of the blood cells occurred, small fragments detached from the mother thrombus and flew downstream, or the fibrin core of the thrombus was exposed. The results indicate the usefulness of angioscopy for the dynamic and serial investigation of thrombosis and thrombolysis. PMID:3766368

  17. Angioplasty and stent placement -- peripheral arteries

    MedlinePlus

    Percutaneous transluminal angioplasty - peripheral artery; PTA - peripheral artery; Angioplasty - peripheral arteries; Iliac artery -angioplasty; Femoral artery - angioplasty; Popliteal artery - angioplasty; Tibial artery - angioplasty; ...

  18. A remote drip infusion monitoring system employing Bluetooth.

    PubMed

    Amano, Hikaru; Ogawa, Hidekuni; Maki, Hiromichi; Tsukamoto, Sosuke; Yonezawa, Yoshiharu; Caldwell, W Morton

    2012-01-01

    We have developed a remote drip infusion monitoring system for use in hospitals. The system consists of several infusion monitoring devices and a central monitor. The infusion monitoring device employing a Bluetooth module can detect the drip infusion rate and an empty infusion solution bag, and then these data are sent to the central monitor placed at the nurses' station via the Bluetooth. The central monitor receives the data from several infusion monitoring devices and then displays graphically them. Therefore, the developed system can monitor intensively the drip infusion situation of the several patients at the nurses' station.

  19. External quantification of myocardial perfusion by exponential infusion of positron-emitting radionuclides.

    PubMed

    Hack, S N; Eichling, J O; Bergmann, S R; Welch, M J; Sobel, B E

    1980-11-01

    A technique was developed and evaluated using the exponential infusion of positron-emitting diffusible tracers to quantitate myocardial perfusion. The approach employs a parameter that rapidly reaches a constant value as a function of tracer delivery rate, isotope decay constant, and the monotonically increasing tissue radioactivity. Isolated rabbit hearts with controlled flow were used to evaluate the approach, because tracer kinetics in such preparations mimic those in vivo. Accordingly, exponential infusions of H2 15O and [11C]butanol were administered to 25 isolated rabbit hearts perfused with Krebs-Henseleit solution (KH) alone or KH enriched with erythrocytes (KH-RBC, hematocrit = 40). With flow varied from 1.2 to 5 ml/g per min in eight KH hearts infused with H2 15O, actual and estimated flow correlated closely (r = 0.95, n = 52 determinations). For the KH-RBC hearts, flow was varied from 0.3 to 1.5 ml/g per min. Actual and estimated flow correlated significantly for both the 14 KH-RBC hearts infused with H2 15O (r = 0.90, n = 89 determinations) and the 3 KH-RBC hearts infused with [11C]butanol (r = 0.93, n = 13 determinations). In addition, the required exponentially increasing arterial tracer concentrations were shown to be attainable in vivo in dogs and rhesus monkeys after intravenous exponential administrations of tracer. The results suggest that the approach developed employing exponential tracer infusion permits accurate measurement of myocardial perfusion and that it should prove useful in the noninvasive measurement of regional myocardial perfusion in vivo by positron emission tomography.

  20. Initial Observations of the Effects of Calcium Chloride Infusions in Pediatric Patients with Low Cardiac Output.

    PubMed

    Averin, Konstantin; Villa, Chet; Krawczeski, Catherine D; Pratt, Jesse; King, Eileen; Jefferies, John L; Nelson, David P; Cooper, David S; Ryan, Thomas D; Sawyer, Jaclyn; Towbin, Jeffrey A; Lorts, Angela

    2016-03-01

    Myocardial contractility and relaxation are highly dependent on calcium homeostasis. Immature myocardium, as in pediatric patients, is thought to be more dependent on extracellular calcium for optimal function. For this reason, intravenous calcium chloride infusions may improve myocardial function in the pediatric patient. The objectives of this study were to report the hemodynamic changes seen after administration of continuous calcium chloride to critically ill children. We retrospectively identified pediatric patients (newborn to 17 years old) with hemodynamic instability admitted to the cardiac ICU between May 2011 and May 2012 who received a continuous infusion of calcium chloride. The primary outcome was improvement in cardiac output, assessed by arterial-mixed venous oxygen saturation (A-V) difference. Sixty-eight patients, mean age 0.87 ± 2.67 years, received a total of 116 calcium infusions. Calcium chloride infusions resulted in significant improvements in primary and secondary measures of cardiac output at 2 and 6 h. Six hours after calcium initiation, A-V oxygen saturation difference decreased by 7.4 % (32.6 ± 2.1 to 25.2 ± 2.0 %, p < 0.001), rSO2 increased by 5.5 % (63.1 vs 68.6 %, p < 0.001), and serum lactate decreased by 0.9 mmol/l (3.3 vs 2.4 mmol/l, p < 0.001) with no change in HR (149.1 vs 145.6 bpm p = 0.07). Urine output increased 0.66 ml/kg/h in the 8-h period after calcium initiation when compared to pre-initiation (p = 0.003). Neonates had the strongest evidence of effectiveness with other age groups trending toward significance. Calcium chloride infusions improve markers of cardiac output in a heterogenous group of pediatric patients in a cardiac ICU. Neonates appear to derive the most benefit from utilization of these infusions.

  1. Successful Thrombolysis and Spasmolysis of Acute Leg Ischemia after Accidental Intra-arterial Injection of Dissolved Flunitrazepam Tablets

    SciTech Connect

    Radeleff, B. Stampfl, U.; Sommer, C.-M.; Bellemann, N.; Hyhlik-Duerr, A.; Weber, M.-A.; Boeckler, D.; Kauczor, H.-U.

    2011-10-15

    A 37-year-old man with known intravenous drug abuse presented in the surgical ambulatory care unit with acute leg ischemia after accidental intra-arterial injection of dissolved flunitrazepam tablets into the right femoral artery. A combination of anticoagulation, vasodilatation, and local selective and superselective thrombolysis with urokinase was performed to salvage the leg. As a result of the severe ischemia-induced pain, the patient had to be monitored over the complete therapy period on the intensive care unit with permanent administration of intravenous fluid and analgetics. We describe the presenting symptoms and the interventional technique, and we discuss the recent literature regarding the management of accidental intra-arterial injection of dissolved flunitrazepam tablets.

  2. Platelet--arterial synthetic graft interaction and its modification

    SciTech Connect

    Callow, A.D.; Connolly, R.; O'Donnell, T.F. Jr.; Gembarowicz, R.; Keough, E.; Ramberg-Laskaris, K.; Valeri, C.R.

    1982-11-01

    We compared the in vivo platelet reactivity of two commonly used clinical grafts, Dacron and expanded polytetrafluoroethylene (PTFE), with that of a control autogenous artery graft and assessed whether platelet reactivity was modified by the platelet-antiaggregating agent prostacyclin (PGI2) (epoprostenol). Grafts were randomly placed into the carotid arteries of 21 baboons. Platelets labeled with /sup 111/In were infused within one hour after implantation graft for gamma camera scanning of platelet uptake. The accumulation of platelets on Dacron grafts began almost immediately after injection and reached a peak after one to two hours. The PTFE and control autogenous artery grafts accumulated comparable small amounts of platelets. Prostacyclin was then infused in a second series of baboons with Dacron grafts, at a rate of 150 to 200 ng/kg/min. It prevented the usual platelet uptake when administered concomitant with graft implantation and reduced previously established platelet activity.

  3. Plasmin-dependent elimination of the growth-factor-like domain in urokinase causes its rapid cellular uptake and degradation.

    PubMed Central

    Poliakov, A; Tkachuk, V; Ovchinnikova, T; Potapenko, N; Bagryantsev, S; Stepanova, V

    2001-01-01

    Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in concert to mediate pericellular proteolysis and to stimulate intracellular signalling responsible for cell migration and proliferation. uPA is composed of three domains, a proteolytic domain (PD), a kringle domain (KD) and a growth-factor-like domain (GFD), the last of which mediates the interaction with uPAR. We demonstrate that uPA, associated with the surface of U937 cells, undergoes plasmin-mediated cleavage of the Lys(46)-Ser(47) bond with elimination of the GFD. Using recombinant forms of uPA, we show that a uPA variant lacking the GFD (r-uPADeltaGFD) and unable to associate with uPAR is rapidly cleared from the cell surface. Binding and internalization of r-uPADeltaGFD are markedly decreased in the presence of 39 kDa receptor-associated protein (RAP), the antagonist of several endocytic receptors of the low-density lipoprotein receptor family, suggesting that this protein clearance pathway is used for r-uPADeltaGFD. In contrast with rapidly internalized r-uPADeltaGFD, the intact recombinant single-chain urokinase with wild-type structure (r-uPAwt) bound to uPAR is retained on the cell surface. Soluble uPAR protects uPA from cleavage by plasmin that results in the elimination of GFD, suggesting that uPAR might protect cell-bound urokinase from plasmin-mediated cleavage between the GFD and KD and subsequent degradation. PMID:11311125

  4. Comparison of histamine and hyperosmotic arabinose infusion on brain capillary permeability to hydrophilic solutes

    SciTech Connect

    Lucchesi, K.J.

    1986-03-01

    The effect of bilateral intracarotid infusion of histamine (HA) on capillary permeability-surface area products (PS) of two metabolically inert tracers was determined and compared to that of L(+)arabinose (ARAB) in rat brain. Ringer's solution alone, or with 1 mg/kg HA diphosphate or 1.6M ARAB added, was infused (0.9 ml over 0.5 min) into each external carotid artery (CA). Five minutes later, a bolus of /sup 14/C-sucrose and /sup 3/H-L-glucose was injected i.v. Estimates of PS for both tracers were computed by the method of Ohno et al after brain concentration was corrected for tracer within cerebral blood vessels. Brain blood volume, based on the /sup 14/C-dextran space, was the same (.016 ml/g) in discrete cortical and midbrain regions of all rats except those treated with ARAB. The latter yielded .033 ml/g, presumably due to dextran extravasation. Infusion of ARAB, HA and Ringer's increased the PS's of sucrose and L-glucose by 10x, 8x, and 3x in brain regions perfused by the internal CA's. The ratio, PS-sucrose/PS-L-glucose was unchanged by any treatment. Both ARAB and HA caused transient falls in arterial pressure, but only ARAB caused deaths (3 of 9 rats). While as effective as ARAB in opening the blood-brain barrier, HA may be safer than hyperosmotic shock to enhance delivery of chemotherapeutic agents to brain tumors.

  5. Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator.

    PubMed

    Frederickson, Martyn; Callaghan, Owen; Chessari, Gianni; Congreve, Miles; Cowan, Suzanna R; Matthews, Julia E; McMenamin, Rachel; Smith, Donna-Michelle; Vinković, Mladen; Wallis, Nicola G

    2008-01-24

    Fragment-based lead discovery has been applied to urokinase-type plasminogen activator (uPA). The (R)-enantiomer of the orally active drug mexiletine 5 (a fragment hit from X-ray crystallographic screening) was the chemical starting point. Structure-aided design led to elaborated inhibitors that retained the key interactions of (R)-5 while gaining extra potency by simultaneously occupying neighboring regions of the active site. Subsequent optimization led to 15, a potent, selective, and orally bioavailable inhibitor of uPA. PMID:18163548

  6. Serum soluble urokinase-type plasminogen activator receptor levels in male patients with acute exacerbation of schizophrenia.

    PubMed

    Genc, Abdullah; Kalelioglu, Tevfik; Karamustafalioglu, Nesrin; Tasdemir, Akif; Genc, Esra Sena; Akkus, Mustafa; Emul, Murat

    2016-02-28

    Inflammatory abnormalities have been shown in the pathogenesis of schizophrenia. Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein that is measurable in the circulating blood and reflects the inflammation in the body. We aimed to investigate serum suPAR levels in patients with schizophrenia who were in acute state and to compare with healthy controls. Forty five patients and 43 healthy controls were included in the study. We found no significant difference in suPAR levels between patients and controls, suggesting that suPAR as an inflammatory marker does not have a role in the inflammatory process of acute schizophrenia.

  7. Meta-analysis of the urokinase gene 3′-UTR T/C polymorphism and susceptibility to urolithiasis

    PubMed Central

    LI, DAWEI; LIU, JIKAI; REN, JUCHAO; YAN, LEI; LIU, HAINAN; XU, ZHONGHUA

    2013-01-01

    Urokinase is involved in the processes of initiating urinary stones. Several published case-control studies have examined the relationship of urokinase gene 3′-untranslated region (3′-UTR) T/C polymorphism and urolithiasis, but yielded inconsistent findings. In this study, a comprehensive meta-analysis was conducted by pooling relevant studies to obtain reliable conclusions. Studies focusing on the association between urokinase gene 3′-UTR T/C polymorphism and urolithiasis were retrieved through PubMed, Medline, Web of Science and the China National Knowledge Infrastructure platform without any limit on language, until October 2012. Four independent articles were eventually identified as eligible for the final meta-analysis, involving 1,195 subjects. Crude odds ratios (ORs), as well as 95% confidence intervals (CIs), were assessed for the association by either fixed- or random-effects models using RevMan 5.0 software. Significant associations were noted in the ‘TC vs. CC’ codominant model for total population (OR=2.53; 95% CI, 1.43–4.46; P=0.001), Asian population (OR=2.46; 95% CI, 1.38–4.40; P=0.002), male (OR=2.98; 95% CI, 1.43–6.21; P=0.004), Hardy-Weinberg equilibrium (HWE) (OR=2.46; 95% CI, 1.38–4.40; P=0.002) and recurrence (OR=2.66; 95% CI, 1.51–4.67; P=0.00). Statistically significant associations were also observed in the ‘TT+TC vs. CC’ dominant model for the Asian, male, HWE and recurrence population (P<0.05). Additionally, a significant difference was detected in the ‘T vs. C’ allele model for HWE. However, there were no associations in either the ‘TT vs. CC’ codominant model or ‘TT vs. TC+CC’ recessive model. In conclusion, the present meta-analysis suggests that urokinase gene T allele may increase the susceptibility of urolithiasis. PMID:24648951

  8. Development of individual insulin infusion profiles for open loop infusion systems.

    PubMed

    Strack, T; Krause, U; Schulz, G; Beyer, J; Beutelspacher, F; Nagel, J

    1984-04-01

    A computer controlled syringe-type insulin infusion pump storing up to 254 different infusion rates, eight different meal programs and two different basal rates automatically changeable during 24 h in EPROM was used for insulin infusion applying a wavy step profile. This profile approaching the physiological postprandial insulin secretion of the B-cell was calculated by an algorithm following the biphasic insulin secretion model proposed by E. Cerasi . The computer program for the open loop infusion device simulated the feed-back structure of a closed loop insulin secretion control by an algorithm based upon a theoretical postprandial blood sugar profile. Fifteen unstable juvenile onset insulin requiring diabetics could be well controlled after two to three days of an intravenous open loop insulin infusion program. The programs consisted of two constant basal rates and superimposed wavy step profile programs activated at the beginning of each meal. The preabsorptive bolus or cephalic phase was an additional tool both for improved postprandial blood sugar control and further reduction of insulin consumption. The programmable insulin infusion device proved as a valuable tool for the study of a sophisticated insulin infusion profile suitable as well for open loop as for closed loop insulin infusion systems.

  9. Inhibitors of urokinase type plasminogen activator and cytostatic activity from crude plants extracts.

    PubMed

    Zha, Xueqiang; Diaz, Ricardo; Franco, Jose Javier Rosado; Sanchez, Veronica Forbes; Fasoli, Ezio; Barletta, Gabriel; Carvajal, Augusto; Bansal, Vibha

    2013-01-01

    In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC₅₀ values. The chloroform extract showed the lowest IC₅₀ value (3.52 µg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study.

  10. Urokinase-coated chitosan nanoparticles for thrombolytic therapy: preparation and pharmacodynamics in vivo.

    PubMed

    Jin, Hai-jiang; Zhang, Hao; Sun, Min-li; Zhang, Bai-gen; Zhang, Ji-wei

    2013-11-01

    Blood reperfusion of affected limbs is the most effective therapy for peripheral vascular thrombotic disease, restoring nutrition and blood flow to threatened tissues. Because it is more cost-effective than other thrombolytics, urokinase (UK) is widely used to treat venous thrombosis in China. However, its use is limited because of the risk of UK-related hemorrhagic complications. UK-coated nanoparticles (NPs) may decrease adverse effects while simultaneously increasing thrombolytic benefits. The aim of this study was to combine the sustained-release properties of NPs with the clinical benefits of catheter-directed thrombolysis (CDT) to create a promising new therapy. NPs were prepared via self-assembled chitosan and tripolyphosphate, introduced into a thrombosis model in New Zealand white rabbits, and the ratio of the residual thrombus cross-sectional area to the vascular cross-sectional area was calculated. The NPs had a drug-bearing efficiency of 14.5 ± 1.3%, an encapsulation efficiency of 94.8 ± 2.1% while the particle size of UK-coated NPs was 236 nm. Transmission electron microscopy results showed that the shape of the NPs were spherical and regular. Whether delivered by intravenation or catheter, UK-coated NPs produced a significant increase in the thrombolytic effect compared with free UK and confirmed the superiority of CDT for improving clot lysis over drug-induced systemic thrombolysis. The intravenous NPs caused an abnormal increase in fibrinogen. In conclusion, a water-soluble UK-WCS-NP suspension with good encapsulation efficiency was easily prepared UK-WCS-NPs were capable of maintaining UK activity, provided sustained-release of UK and exhibited better thrombolytic function than free UK. PMID:23728739

  11. Probing Binding and Cellular Activity of Pyrrolidinone and Piperidinone Small Molecules Targeting the Urokinase Receptor

    PubMed Central

    Mani, Timmy; Liu, Degang; Zhou, Donghui; Li, Liwei; Knabe, William Eric; Wang, Fang; Oh, Kyungsoo; Meroueh, Samy O.

    2014-01-01

    The urokinase receptor (uPAR) is a cell-surface protein that is part of an intricate web of transient and tight protein interactions that promote cancer cell invasion and metastasis. Here we evaluate the binding and biological activity of a new class of pyrrolidinone (3) and piperidinone (4) compounds, along with derivatives of previously-identified pyrazole (1) and propylamine (2) compounds. Competition assays revealed that the compounds displaced a fluorescently-labeled peptide (AE147-FAM) with inhibition constant Ki ranging from 6 to 63 μM. Structure-based computational pharmacophore analysis followed by extensive explicit-solvent molecular dynamics simulations and free energy calculations suggested pyrazole-based 1a and piperidinone-based 4 adopt different binding modes, despite their similar two-dimensional structures. In cells, compounds 1b and 1f showed significant inhibition of breast MDA-MB-231 and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but 4b exhibited no cytotoxicity even at concentrations of 100 μM. 1f impaired MDA-MB-231 invasion, adhesion, and migration in a concentration-dependent manner, while 4b inhibited only invasion. 1f inhibited gelatinase (MMP-9) activity in a concentration-dependent manner, while 4b showed no effect suggesting different mechanisms for inhibition of cell invasion. Signaling studies further highlighted these differences, showing that pyrazole compounds completely inhibited ERK phosphorylation and impaired HIF1α and NF-κB signaling, while pyrrolidinone and piperidinone (3 and 4b) had no effect. Annexin V staining suggested that the effect of pyrazole-based 1f on proliferation was due to cell killing through an apoptotic mechanism. PMID:24115356

  12. Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Patients With Schizophrenia

    PubMed Central

    Nielsen, Jimmi; Røge, Rasmus; Pristed, Sofie Gry; Viuff, Anne Grethe; Ullum, Henrik; Thørner, Lise Wegner; Werge, Thomas; Vang, Torkel

    2015-01-01

    Background: The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein that can be measured in blood samples and reflects the levels of inflammatory activity. It has been associated with mortality and the development of type 2 diabetes and cardiovascular disease. Methods: suPAR levels in patients with schizophrenia were compared to healthy controls from the Danish Blood Donor Study. SuPAR levels were dichotomized at >4.0 ng/ml, which is considered the threshold for low grade inflammation. A multiple logistic regression model was used and adjusted for age, sex, and current smoking. Results: In total we included 1009 subjects, 105 cases with schizophrenia (10.4%) and 904 controls (89.6%). The mean suPAR values were 4.01 ng/ml (SD = 1.43) for the cases vs 1.91 ng/ml (SD = 1.35) for the controls (P < .001). Multiple logistic regression with odds ratio (OR) for suPAR levels >4.0 ng/ml yielded: schizophrenia, OR: 46.15 95% CI 22.69–93.87, P < .001; age, OR: 1.02 95% CI 0.99–1.02, P = .15; male sex, OR: 0.70 95% CI 0.35–1.36, P = .29; and current smoking, OR: 3.51 95% CI 1.78–6.94, P < .001. Conclusions: Patients with schizophrenia had significantly higher suPAR levels than healthy controls. Further studies are warranted to clarify if elevated suPAR levels are involved in the pathophysiology of schizophrenia and/or the increased mortality found in patients with schizophrenia. PMID:25154621

  13. A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation.

    PubMed

    Fuentes, Rudy E; Zaitsev, Sergei; Ahn, Hyun Sook; Hayes, Vincent; Kowalska, M Anna; Lambert, Michele P; Wang, Yuhuan; Siegel, Donald L; Bougie, Daniel W; Aster, Richard H; Myers, Daniel D; Stepanova, Victoria; Cines, Douglas B; Muzykantov, Vladimir R; Poncz, Mortimer

    2016-02-01

    The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule-delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi. PMID:26690701

  14. Urokinase-Type Plasminogen Activator Deficiency Promotes Neoplasmatogenesis in the Colon of Mice123

    PubMed Central

    Karamanavi, Elisavet; Angelopoulou, Katerina; Lavrentiadou, Sophia; Tsingotjidou, Anastasia; Abas, Zaphiris; Taitzoglou, Ioannis; Vlemmas, Ioannis; Erdman, Suzan E.; Poutahidis, Theofilos

    2014-01-01

    Urokinase-type plasminogen activator (uPA) participates in cancer-related biologic processes, such as wound healing and inflammation. The present study aimed to investigate the effect of uPA deficiency on the long-term outcome of early life episodes of dextran sodium sulfate (DSS)–induced colitis in mice. Wild-type (WT) and uPA-deficient (uPA−/−) BALB/c mice were treated with DSS or remained untreated. Mice were necropsied either 1 week or 7 months after DSS treatment. Colon samples were analyzed by histopathology, immunohistochemistry, ELISA, and real-time polymerase chain reaction. At 7 months, with no colitis evident, half of the uPA−/− mice had large colonic polypoid adenomas, whereas WT mice did not. One week after DSS treatment, there were typical DSS-induced colitis lesions in both WT and uPA−/− mice. The affected colon of uPA−/− mice, however, had features of delayed ulcer re-epithelialization and dysplastic lesions of higher grade developing on the basis of a significantly altered mucosal inflammatory milieu. The later was characterized by more neutrophils and macrophages, less regulatory T cells (Treg), significantly upregulated cytokines, including interleukin-6 (IL-6), IL-17, tumor necrosis factor-α, and IL-10, and lower levels of active transforming growth factor–β1 (TGF-β1) compared to WT mice. Dysfunctional Treg, more robust protumorigenic inflammatory events, and an inherited inability to produce adequate amounts of extracellular active TGF-β1 due to uPA deficiency are interlinked as probable explanations for the inflammatory-induced neoplasmatogenesis in the colon of uPA−/− mice. PMID:24913672

  15. Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells.

    PubMed

    Alfano, Daniela; Gorrasi, Anna; Li Santi, Anna; Ricci, Patrizia; Montuori, Nunzia; Selleri, Carmine; Ragno, Pia

    2015-09-01

    The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3'untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo.

  16. Effect of urokinase-type plasminogen activator system in gastric cancer with peritoneal metastasis

    PubMed Central

    DING, YOUCHENG; ZHANG, HUI; LU, AIGUO; ZHOU, ZHUQING; ZHONG, MINGAN; SHEN, DONGWEI; WANG, XUJING; ZHU, ZHENGGANG

    2016-01-01

    Peritoneal metastasis is a primary cause of mortality in patients with gastric cancer. Urokinase-type plasminogen activator (uPA) has been demonstrated to be associated with tumor cell metastasis through the degradation of the extracellular matrix. The present study aimed to investigate the mechanisms of the uPA system in gastric cancer with peritoneal metastasis. Expression of uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in four gastric cell lines (AGS, SGC7901, MKN45 and MKN28) was measured by semiquantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting. uPA activity was detected using a uPA activity kit. Peritoneal implantation models of rats were established by injecting four gastric cancer cell lines for the selection of the cancer cells with a high planting potential. Biological behaviors, including adhesion, migration and invasion, were determined using a methyl thiazolyl tetrazolium assay. Expression of the uPA system was observed to be highest in the SGC7901 cells among the four gastric cell lines. uPA activity was observed to be highest in the MKN45 cells and lowest in the AGS cells. Furthermore, peritoneal implantation analysis demonstrated that no peritoneal tumors were identified in the AGS cells, whilst the tumor masses observed in the SGC7901 and MKN45 cells were of different sizes. The survival times of the rats injected with the MKN28 and SGC7901 cells were longer than those of the rats injected with the MKN45 cells. Antibodies for uPA, uPAR and PAI-1 in the uPA system had the ability to inhibit the adhesion, migration and invasion of peritoneal metastasis in the gastric cancer cells. The results of the present study demonstrated that the uPA system was positively associated with peritoneal metastasis in gastric cancer. PMID:27313768

  17. Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

    PubMed Central

    Zha, Xueqiang; Diaz, Ricardo; Franco, Jose Javier Rosado; Sanchez, Veronica Forbes; Fasoli, Ezio; Barletta, Gabriel; Carvajal, Augusto; Bansal, Vibha

    2014-01-01

    In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC50 values. The chloroform extract showed the lowest IC50 value (3.52 μg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study. PMID:23896619

  18. A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

    PubMed Central

    Fuentes, Rudy E.; Zaitsev, Sergei; Ahn, Hyun Sook; Hayes, Vincent; Kowalska, M. Anna; Lambert, Michele P.; Wang, Yuhuan; Siegel, Donald L.; Bougie, Daniel W.; Aster, Richard H.; Myers, Daniel D.; Stepanova, Victoria; Cines, Douglas B.; Muzykantov, Vladimir R.; Poncz, Mortimer

    2015-01-01

    The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule–delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi. PMID:26690701

  19. Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation.

    PubMed

    Cunningham, Orla; Campion, Suzanne; Perry, V Hugh; Murray, Carol; Sidenius, Nicolai; Docagne, Fabian; Cunningham, Colm

    2009-12-01

    The urokinase plasminogen activator (uPA) receptor (uPAR) is a GPI-linked cell surface protein that facilitates focused plasmin proteolytic activity at the cell surface. uPAR has been detected in macrophages infiltrating the central nervous system (CNS) and soluble uPAR has been detected in the cerebrospinal fluid during a number of CNS pathologies. However, its expression by resident microglial cells in vivo remains uncertain. In this work, we aimed to elucidate the murine CNS expression of uPAR and uPA as well as that of tissue plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) during insults generating distinct and well-characterized inflammatory responses; acute intracerebral lipopolysaccharide (LPS), acute kainate-induced neurodegeneration, and chronic neurodegeneration induced by prion disease inoculation. All three insults induced marked expression of uPAR at both mRNA and protein level compared to controls (naïve, saline, or control inoculum-injected). uPAR expression was microglial in all cases. Conversely, uPA transcription and activity was only markedly increased during chronic neurodegeneration. Dissociation of uPA and uPAR levels in acute challenges is suggestive of additional proteolysis-independent roles for uPAR. PAI-1 was most highly expressed upon LPS challenge, whereas tissue plasminogen activator mRNA was constitutively present and less responsive to all insults studied. These data are novel and suggest much wider involvement of the uPAR/uPA system in CNS function and pathology than previously supposed. PMID:19459212

  20. Urokinase-type plasminogen activator receptor modulates epileptogenesis in mouse model of temporal lobe epilepsy.

    PubMed

    Ndode-Ekane, Xavier Ekolle; Pitkänen, Asla

    2013-06-01

    Mutation in Plaur gene encoding urokinase-type plasminogen activator receptor (uPAR) results in epilepsy and autistic phenotype in mice. In humans, a single nucleotide polymorphism in PLAUR gene represents a risk for autism spectrum disorders. Importantly, the expression of uPAR is elevated in the brain after various epileptogenic insults like traumatic brain injury and status epilepticus. So far, the consequences of altered uPAR expression on brain networks are poorly known. We tested a hypothesis that uPAR regulates post-injury neuronal reorganization and consequent functional outcome, particularly epileptogenesis. Epileptogenesis was induced by intrahippocampal injection of kainate in adult male wild type (Wt) or uPAR knockout (uPAR-/-) mice, and animals were monitored with continuous (24/7) video-electroencephalogram for 30 days. The severity of status epilepticus did not differ between the genotypes. The spontaneous electrographic seizures which developed were, however, longer and their behavioral manifestations were more severe in uPAR-/- than Wt mice. The more severe epilepsy phenotype in uPAR-/- mice was associated with delayed but augmented inflammatory response and more severe neurodegeneration in the hippocampus. Also, the distribution of newly born cells in the dentate gyrus was more scattered, and the recovery of hippocampal blood vessel length from status epilepticus-induced damage was compromised in uPAR-/- mice as compared to Wt mice. Our data demonstrate that a deficiency in uPAR represents a mechanisms which results in the development of a more severe epilepsy phenotype and progressive brain pathology after status epilepticus. We suggest that uPAR represents a rational target for disease-modifying treatments after epileptogenic brain insults. PMID:23263886

  1. Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells

    PubMed Central

    Alfano, Daniela; Gorrasi, Anna; Li Santi, Anna; Ricci, Patrizia; Montuori, Nunzia; Selleri, Carmine; Ragno, Pia

    2015-01-01

    The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3′untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo. PMID:26082201

  2. The urokinase inhibitor p-aminobenzamidine inhibits growth of a human prostate tumor in SCID mice.

    PubMed

    Billström, A; Hartley-Asp, B; Lecander, I; Batra, S; Astedt, B

    1995-05-16

    Malignant cells possess a high degree of proteolytic activity in which the plasminogen activator system plays an important role. An increased expression of urokinase type plasminogen activator (uPA) is of significance for degradation of the extracellular tumor matrix, facilitating invasiveness and growth. Inhibition of the active site of uPA makes it possible to evaluate the significance of uPA in tumor growth. We report here experiments on a uPA-producing human prostate xenograft (DU 145) using a competitive inhibitor of uPA, p-aminobenzamidine. In vitro experiments with DU 145 cells showed that p-aminobenzamidine caused a dose-dependent inhibition of uPA activity. DU 145 cells were inoculated s.c. in SCID mice and, once tumors were established, treatment with p-aminobenzamidine added to drinking water was started and lasted for 23 days. Mice receiving 250 mg/kg/day of p-aminobenzamidine showed a clear decrease in tumor-growth rate compared to the non-treated mice, resulting in 64% lower final tumor weight. In addition, uPA-antigen levels in the membrane fractions of DU 145 tumors from p-aminobenzamidine-treated mice were found to be decreased by 59%. We also show that p-aminobenzamidine has an anti-proliferative effect in cell culture at low cell number, correlating with a dose-dependent decrease in uPA production. In conclusion, we show that a low-molecular-weight uPA-inhibitor, p-aminobenzamidine, has a growth-inhibitory effect on a solid uPA-producing tumor. PMID:7759160

  3. Extracellular alpha 6 integrin cleavage by urokinase-type plasminogen activator in human prostate cancer

    PubMed Central

    Demetriou, Manolis C.; Pennington, Michael E.; Nagle, Raymond B.; Cress, Anne E.

    2009-01-01

    During human prostate cancer progression, the integrin α6β1 (laminin receptor) is expressed on the cancer cell surface during invasion and in lymph node metastases. We previously identified a novel structural variant of the α6 integrin called α6p. This variant was produced on the cell surface and was missing the β-barrel extracellular domain. Using several different concentrations of amiloride, aminobenzamidine and PAI-1 and the urokinase-type plasminogen activator (uPA) function-blocking antibody (3689), we showed that uPA, acting as a protease, is responsible for production of α6p. We also showed that addition of uPA in the culture media of cells that do not produce α6p, resulted in a dose-dependent α6p production. In contrast, the addition of uPA did not result in the cleavage of other integrins. Using α2-antiplasmin and plasmin depleted media, we observed that uPA cleaves the α6 integrin directly. Further, 12-o-tetradecanoyl-phorbol-13-acetate (TPA) induced the production of α6p, and this induction was abolished by PAI-1 but not α2-antiplasmin. Finally, the α6p integrin variant was detected in invasive human prostate carcinoma tissue indicating that this is not a tissue culture phenomenon. These data, taken together, suggest that this is a novel function of uPA, that is, to remove the β-barrel ligand-binding domain of the integrin while preserving its heterodimer association. PMID:15023541

  4. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.

    PubMed

    LeBeau, Aaron M; Sevillano, Natalia; King, Mandy L; Duriseti, Sai; Murphy, Stephanie T; Craik, Charles S; Murphy, Laura L; VanBrocklin, Henry F

    2014-01-01

    Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications. PMID:24505235

  5. Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

    PubMed Central

    Zhuo, Jingli; Tan, Ee Hong; Yan, Benedict; Tochhawng, Lalchhandami; Jayapal, Manikandan; Koh, Shiuan; Tay, Hwee Kee; Maciver, Sutherland K.; Hooi, Shing Chuan; Salto-Tellez, Manuel; Kumar, Alan Prem; Goh, Yaw Chong; Lim, Yaw Chyn; Yap, Celestial T.

    2012-01-01

    Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin’s influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. PMID:22927998

  6. Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation.

    PubMed

    Cunningham, Orla; Campion, Suzanne; Perry, V Hugh; Murray, Carol; Sidenius, Nicolai; Docagne, Fabian; Cunningham, Colm

    2009-12-01

    The urokinase plasminogen activator (uPA) receptor (uPAR) is a GPI-linked cell surface protein that facilitates focused plasmin proteolytic activity at the cell surface. uPAR has been detected in macrophages infiltrating the central nervous system (CNS) and soluble uPAR has been detected in the cerebrospinal fluid during a number of CNS pathologies. However, its expression by resident microglial cells in vivo remains uncertain. In this work, we aimed to elucidate the murine CNS expression of uPAR and uPA as well as that of tissue plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) during insults generating distinct and well-characterized inflammatory responses; acute intracerebral lipopolysaccharide (LPS), acute kainate-induced neurodegeneration, and chronic neurodegeneration induced by prion disease inoculation. All three insults induced marked expression of uPAR at both mRNA and protein level compared to controls (naïve, saline, or control inoculum-injected). uPAR expression was microglial in all cases. Conversely, uPA transcription and activity was only markedly increased during chronic neurodegeneration. Dissociation of uPA and uPAR levels in acute challenges is suggestive of additional proteolysis-independent roles for uPAR. PAI-1 was most highly expressed upon LPS challenge, whereas tissue plasminogen activator mRNA was constitutively present and less responsive to all insults studied. These data are novel and suggest much wider involvement of the uPAR/uPA system in CNS function and pathology than previously supposed.

  7. Increased dietary sodium alters Fos expression in the lamina terminalis during intravenous angiotensin II infusion.

    PubMed

    Bealer, Steven L; Metcalf, Cameron S; Heyborne, Ryan

    2007-03-01

    These studies examined the effects of increased dietary sodium on expression of Fos, the protein product of c-fos, in forebrain structures in the rat following intravenous infusion with angiotensin II (AngII). Animals were provided with either tap water (Tap) or isotonic saline solution (Iso) as their sole drinking fluid for 3-5 weeks prior to testing. Rats were then implanted with catheters in a femoral artery and vein. The following day, the conscious, unrestrained animals received iv infusion of either isotonic saline (Veh), AngII, or phenylephrine (Phen) for 2 h. Blood pressure and heart rate were monitored continuously throughout the procedure. Brains were subsequently processed for evaluation of Fos-like immunoreactivity (Fos-Li IR) in the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO), and the median preoptic nucleus (MnPO). Fos-Li IR was significantly increased in the SFO and OVLT of animals consuming both Tap and Iso following AngII, but not Phen, compared to Veh infusions. Furthermore, Fos-Li IR in the MnPO was increased following AngII infusion in rats consuming a high sodium diet, but not in animals drinking Tap. These data suggest that increased dietary sodium sensitizes the MnPO neurons to excitatory input from brain areas responding to circulating AngII.

  8. Blood pressure regulation in third-trimester pregnant women receiving tocolytic terbutaline infusion.

    PubMed

    Bremme, K; Eneroth, P; Carsjö, B M; Nilsson, B

    1986-10-01

    Terbutaline (20 micrograms/min) was infused during 30 min in 17 women in whom a manual external manipulation of a breech presentation was going to be attempted. A significant increase in systolic (P = 0.003) and a decrease in diastolic blood pressure (P = 0.04) was noted at the end of the infusion but no change in mean arterial blood pressure was obtained. At the same time aldosterone serum levels had dropped significantly (P = 0.009) and plasma angiotensin II showed a marked increase (P less than 0.001) which continued during the next 30 min. All changes were normalized after the infusion. The angiotensin-converting enzyme activity remained unchanged, as did vasopressin plasma levels. The combined results of terbutaline provocation have been interpreted to mean that blood pressure regulation in third-trimester pregnant women is similar to that in nonpregnant individuals. The increase in dehydroepiandrosterone sulphate (P less than 0.05) noted at the end of infusion was suggested to be related to the blood pressure changes and was unrelated to fluctuations in serum cortisol. The latter steroid increased between 30 and 60 min, e.g. during the manual external manipulation, and was interpreted as being due to maternal stress. PMID:3023154

  9. Different ophthalmic artery origins: Embryology and clinical significance.

    PubMed

    Louw, Louise

    2015-07-01

    This retrospective study gives a summary of ophthalmic artery (OA) variations to serve as guidelines for surgical interventionists and trainees. Pubmed and Medline searches were conducted. The OA usually arises intradurally (superomedial, anteromedial, or rarely superolateral) from the internal carotid artery (ICA). Rare extradural origin (primitive dorsal OA) (PDOA) remnant and extremely rare interdural origin (primitive ventral OA) (PVOA) remnant are of significance when sectioning the dural ring. Rarely, a persistent PDOA with ICA origin, or a PDOA remnant with inferolateral trunk origin, enters the orbit via the superior orbital fissure (SOF) for sole or partial orbital supply. Extremely rare, the PDOA and PVOA persist and form double OAs that arise from the ICA and run via the SOF and optic foramen. Occasionally, the OA arises from the middle meningeal artery (MMA), when both the PDOA and VDOA regress and enter the orbit via the SOF. Sole orbital supply via the external carotid artery (ECA), i.e. meningo-ophthalmic artery and/or MMA branches, or dual OAs (ECA and ICA origins) may occur. Other rare OA origins include anterior or posterior communicating artery; anterior or middle cerebral artery; basilar artery; posterior inferior cerebellar artery; and the carotid bifurcation. Primitive arteries (persistent or remnant), and/or abnormal anastomoses play pivotal roles in manifestations of OA variations. Of clinical importance are orbital collateral routes and dangerous extracranial-intracranial anastomoses. Awareness of OA origins and collateral routes is imperative for transarterial embolizations or infusion chemotherapy in the ECA territory to prevent visual complications.

  10. Hepatic artery injury during left hepatic trisectionectomy for colorectal liver metastasis treated by portal vein arterialization.

    PubMed

    Hokuto, Daisuke; Nomi, Takeo; Yamato, Ichiro; Yasuda, Satoshi; Obara, Shinsaku; Yamada, Takatsugu; Kanehiro, Hiromichi; Nakajima, Yoshiyuki

    2015-01-01

    Portal vein arterialization (PVA) has been applied as a salvage procedure in hepatopancreatobiliary surgeries, including transplantation and liver resection, with revascularization for malignancies. Here we describe the use PVA as a salvage procedure following accidental injury of the hepatic artery to the remnant liver occurred during left hepatic trisectionectomy for colorectal liver metastases (CRLM). A 60-year-old man with cancer of the sigmoid colon and initially unresectable CRLM received 11 cycles of hepatic arterial infusion chemotherapy with 5-fluorouracil (1500mg/week), after which CRLM was downstaged to resectable. One month after laparoscopic sigmoidectomy, a left trisectionectomy and wedge resection of segment 6 were performed. The posterior branch of the right hepatic artery, the only feeding artery to the remnant liver, was injured and totally dissected. Because microsurgical reconstruction of the artery was impossible, PVA was used; PVA is the sole known procedure available when hepatic artery reconstruction is impossible. The patient then suffered portal hypertension, and closure of arterio-portal anastomosis using an interventional technique with angiography was eventually performed on postoperative day 73. Therefore, it is considered that because PVA is associated with severe postoperative portal hypertension, closure of the arterio-portal shunt should be performed as soon as possible on diagnosing portal hypertension. PMID:26197094

  11. Visualization of hepatic arteries with 3D ultrasound during intra-arterial therapies

    NASA Astrophysics Data System (ADS)

    Gérard, Maxime; Tang, An; Badoual, Anaïs.; Michaud, François; Bigot, Alexandre; Soulez, Gilles; Kadoury, Samuel

    2016-03-01

    Liver cancer represents the second most common cause of cancer-related mortality worldwide. The prognosis is poor with an overall mortality of 95%. Moreover, most hepatic tumors are unresectable due to their advanced stage at discovery or poor underlying liver function. Tumor embolization by intra-arterial approaches is the current standard of care for advanced cases of hepatocellular carcinoma. These therapies rely on the fact that the blood supply of primary hepatic tumors is predominantly arterial. Feedback on blood flow velocities in the hepatic arteries is crucial to ensure maximal treatment efficacy on the targeted masses. Based on these velocities, the intra-arterial injection rate is modulated for optimal infusion of the chemotherapeutic drugs into the tumorous tissue. While Doppler ultrasound is a well-documented technique for the assessment of blood flow, 3D visualization of vascular anatomy with ultrasound remains challenging. In this paper we present an image-guidance pipeline that enables the localization of the hepatic arterial branches within a 3D ultrasound image of the liver. A diagnostic Magnetic resonance angiography (MRA) is first processed to automatically segment the hepatic arteries. A non-rigid registration method is then applied on the portal phase of the MRA volume with a 3D ultrasound to enable the visualization of the 3D mesh of the hepatic arteries in the Doppler images. To evaluate the performance of the proposed workflow, we present initial results from porcine models and patient images.

  12. Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin

    NASA Technical Reports Server (NTRS)

    Morrow, B. A.; Keil, L. C.; Severs, W. B.

    1992-01-01

    Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

  13. Cultural Congruence and Infusion Nursing Practice.

    PubMed

    Abitz, Tracey L

    2016-01-01

    The importance of cultural competence in every nursing practice setting in today's world cannot be understated. Unconscious bias can have detrimental effects on therapeutic relationships and health outcomes. Nursing models of cultural competence by Purnell, Leininger, and Campinha-Bacote are reviewed. The Kleinman Model and LEARN Model offer questions and guidelines to facilitate assessment of patients' understanding of illness and treatment. The Infusion Nursing Standards of Practice contains elements of diversity and cultural competence throughout. Self-reflection of one's own values, beliefs, biases, and practice as an infusion nurse will promote the development of cultural competence. PMID:26934161

  14. Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas.

    PubMed

    Benassi, M S; Ponticelli, F; Azzoni, E; Gamberi, G; Pazzaglia, L; Chiechi, A; Conti, A; Spessotto, P; Scapolan, M; Pignotti, E; Bacchini, P; Picci, P

    2007-09-01

    In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant up-regulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. Clearly, the controversial role of PAI-1 protein requires further biological analyses, but evident involvement of uPA/PAI-1 gene overexpression in STS malignancy may highlight a molecular defect useful in discriminating STS high-risk patients. PMID:17523079

  15. The tyrosine phosphatase SHP-2 controls urokinase-dependent signaling and functions in human vascular smooth muscle cells

    SciTech Connect

    Kiyan, Julia Haller, Hermann; Dumler, Inna

    2009-04-01

    The urokinase (uPA)/urokinase receptor (uPAR) multifunctional system is an important mediator of functional behaviour of human vascular smooth muscle cells (VSMC). uPAR associates with platelet-derived growth factor receptor {beta} (PDGFR-{beta}), which serves as a transmembrane adaptor for uPAR in VSMC, to transduce intracellular signaling and initiate functional changes. The precise and rapid propagation of these signaling cascades demands both strict and flexible regulatory mechanisms that remain unexplored. We provide evidence that the tyrosine phosphatase SHP-2 mediates these processes. uPA regulated SHP-2 phosphorylation, catalytic activity, and its co-localization and association with the PDGFR-{beta}. Active PDGFR-{beta} was required for the uPA-induced SHP-2 phosphorylation. uPAR-directed STAT1 pathway was disturbed in cells expressing SHP-2 inactive mutant. Both, cell proliferation and migration were impaired in VSMC with downregulated SHP-2. Elucidating the underlying mechanisms, we found that uPA induced SHP-2 recruitment to lipid rafts. Disruption of rafts abolished uPA-related control of SHP-2 phosphorylation, its association with PDGFR-{beta} and finally the VSMC functional responses. Our results demonstrate that SHP-2 plays an important role in uPA-directed signaling and functional control of human VSMC and suggest that this phosphatase might contribute to the pathogenesis of the uPA-related vascular remodeling.

  16. Selective pulmonary vasodilation by low-dose infusion of adenosine triphosphate in newborn lambs.

    PubMed

    Konduri, G G; Woodard, L L

    1991-07-01

    The systemic and pulmonary vascular effects of adenosine 5'-triphosphate (ATP) were investigated in 12 newborn lambs during normoxia and during alveolar hypoxia (10% oxygen, 5% carbon dioxide, and 85% nitrogen). Lambs had catheters in the descending aorta, main pulmonary artery, and were studied after a 3-day recovery. We infused ATP or an equal volume of saline solution (control) into the right atrial line in doses ranging from 0.01 to 2.5 mumol/kg per minute. In normoxic lambs, ATP caused a significant decrease in pulmonary vascular resistance in doses of 0.08 to 2.5 mumol/kg per minute, and in systemic vascular resistance in doses of 0.3 to 2.5 mumol/kg per minute. Infusion of ATP in hypoxic lambs caused decreases in pulmonary artery pressure and pulmonary vascular resistance in all the doses tested. Systemic vascular resistance decreased, and cardiac output and heart rate increased in doses greater than 0.3 mumol/kg per minute in hypoxic lambs during ATP infusion. The effects of ATP in hypoxic lambs were not blocked by propranolol, indomethacin, or theophylline. Plasma ATP levels in left atrial blood samples did not change significantly during the infusion of ATP. We conclude that ATP is a vasodilator in lambs, and its effects are specific for pulmonary circulation at doses of less than or equal to 0.15 mumol/kg per minute. The vasodilator effects of ATP appear to be independent of P1 purinergic and beta-adrenergic mechanisms, and of prostacyclin synthesis. PMID:1906103

  17. Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats

    PubMed Central

    Damiani, Elisa; Ince, Can; Orlando, Fiorenza; Pierpaoli, Elisa; Cirioni, Oscar; Giacometti, Andrea; Mocchegiani, Federico; Pelaia, Paolo; Provinciali, Mauro; Donati, Abele

    2016-01-01

    Background Sepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis. Methods Adult male Wistar rats were equipped with arterial and venous catheters and received an intravenous infusion of lipopolysaccharide (LPS, serotype O127:B8, 10 mg/kg over 30 minutes) or vehicle (SHAM, n = 6). Two hours later, endotoxemic animals were randomized to receive 10 mL/kg of either 4% HSA (LPS+4%HSA, n = 6), 20% HSA (LPS+20%HSA, n = 6) or 0.9% NaCl (LPS+0.9%NaCl, n = 6). No fluids were given to an additional 6 animals (LPS). Vessel density and perfusion were assessed in the skeletal muscle microcirculation with sidestream dark field videomicroscopy at baseline (t0), 2 hours after LPS injection (t1), after HSA infusion (t2) and 1 hour later (t3). The mean arterial pressure (MAP) and heart rate were recorded. Serum endothelin-1 was measured at t2. Results MAP was stable over time in all groups. The microcirculatory parameters were significantly altered in endotoxemic animals at t1. The infusion of both 4% and 20% HSA similarly increased the perfused vessel density and blood flow velocity and decreased the flow heterogeneity to control values. Microvascular perfusion was preserved in the LPS+20%HSA group at t3, whereas alterations reappeared in the LPS+4%HSA group. Conclusions In a rat model of normotensive endotoxemia, the infusion of 4% or 20% HSA produced a similar acute improvement in the microvascular perfusion in otherwise unresuscitated animals. PMID:26942605

  18. Renal toxicity mediated by continuous infusion of recombinant interleukin-2.

    PubMed

    Ponce, P; Cruz, J; Travassos, J; Moreira, P; Oliveira, J; Melo-Gomes, E; Gouveia, J

    1993-01-01

    Interleukin-2 (IL-2), a potent lymphokine with antitumoral activity, was used in continuous intravenous infusion for 5 days (18,000,000 IU/m2/day) in 9 treatment cycles in 5 patients with metastatic colorectal carcinoma. During the infusion, patients received aggressive fluid replacement titrated by invasive hemodynamic monitoring, aiming at a stable central volemia. Body weight went up an average of 4.5 kg in 5 days, mean arterial blood pressure dropped slightly from day 1 to day 5 (105.4 +/- 11.6 to 86.1 +/- 12.5 mm Hg, p < 0.05), systemic vascular resistance decreased from 1304.7 +/- 242.1 to 871.7 +/- 237.2 dyn/s/cm-5 (p < 0.05), with stable pulmonary capillary wedge pressure, cardiac output and central venous pressure. The urinary output significantly dropped from 1.9 +/- 1.2 to 0.2 +/- 0.1 ml/min (p < 0.05) with very significant rises in serum creatinine from 76.0 +/- 28.3 to 242.2 +/- 144.9 mumol/l (0.86 +/- 0.32 to 2.47 +/- 1.64 mg/dl) and N-acetyl-beta-D-glucosaminidase urinary activity from 4.97 +/- 5.0 to 23.0 +/- 12.1 U/l, and significant decrement of creatinine clearance (1.86 +/- 0.65 to 0.29 +/- 0.27 ml/s or 111.5 +/- 38.9 to 17.1 +/- 16.6 ml/min) and urinary sodium (113.8 +/- 78.3 to 9.0 +/- 6.7 mmol/l). Urine sediment evolved from normal at day 1 to 9.0 +/- 3.7 epithelial cells/mm3 and 6.9 +/- 3.6 brown casts/mm3 (p = 0.001). We concluded that cancer treatment with IL-2 in continuous infusion, even with stable hemodynamics, induces an acute renal failure in most patients treated.

  19. Arginine infusion in patients with septic shock increases nitric oxide production without haemodynamic instability.

    PubMed

    Luiking, Yvette C; Poeze, Martijn; Deutz, Nicolaas E

    2015-01-01

    Arginine deficiency in sepsis may impair nitric oxide (NO) production for local perfusion and add to the catabolic state. In contrast, excessive NO production has been related to global haemodynamic instability. Therefore, the aim of the present study was to investigate the dose-response effect of intravenous arginine supplementation in post-absorptive patients with septic shock on arginine-NO and protein metabolism and on global and regional haemodynamics. Eight critically ill patients with a diagnosis of septic shock participated in this short-term (8 h) dose-response study. L-Arginine-HCl was continuously infused [intravenously (IV)] in three stepwise-increasing doses (33, 66 and 99 μmol·kg-1·h-1). Whole-body arginine-NO and protein metabolism were measured using stable isotope techniques, and baseline values were compared with healthy controls. Global and regional haemodynamic parameters were continuously recorded during the study. Upon infusion, plasma arginine increased from 48±7 to 189±23 μmol·l-1 (means±S.D.; P<0.0001). This coincided with increased de novo arginine (P<0.0001) and increased NO production (P<0.05). Sepsis patients demonstrated elevated protein breakdown at baseline (P<0.001 compared with healthy controls), whereas protein breakdown and synthesis both decreased during arginine infusion (P<0.0001). Mean arterial and pulmonary pressure and gastric mucosal-arterial partial pressure of carbon dioxide difference (Pr-aCO2) gap did not alter during arginine infusion (P>0.05), whereas stroke volume (SV) increased (P<0.05) and arterial lactate decreased (P<0.05). In conclusion, a 4-fold increase in plasma arginine with intravenous arginine infusion in sepsis stimulates de novo arginine and NO production and reduces whole-body protein breakdown. These potential beneficial metabolic effects occurred without negative alterations in haemodynamic parameters, although improvement in regional perfusion could not be demonstrated in the eight

  20. Measuring glycerol turnover, gluconeogenesis from glycerol, and total gluconeogenesis with [2-13C] glycerol: role of the infusion-sampling mode.

    PubMed

    Peroni, O; Large, V; Odeon, M; Beylot, M

    1996-07-01

    Mass isotopomer distribution analysis (MIDA) of glucose during infusion of [2-13C]glycerol is a new method for measuring total gluconeogenesis (GNG). Since this method relies on calculation of the isotopic enrichment (IE) of hepatic triose phosphates (TP), the results should be independent of the sites of tracer infusion and blood sampling. Postabsorptive and starved rats were infused with [2-13C]glycerol and sampled either in the arterial-venous (A-V) or venous-arterial (V-A) modes. Blood was also sampled from the portal vein. In both postabsorptive and starved rats, glycerol turnover rate (Rt) and the percent contribution of glycerol to total glucose production were higher in the A-V mode than in the V-A mode (P < .05). Glycerol IE in portal venous blood was intermediate between IE values observed in peripheral arterial and venous blood. Its use for calculating the contribution of glycerol to glucose production reconciled the results obtained with the two infusion-sampling modes in both postabsorptive and starved rats; this contribution was increased by starvation (P < .01). In postabsorptive rats, total GNG calculated from MIDA of glucose accounted for approximately 50% of glucose production whatever the infusion-sampling mode (A-V, 48.8% +/- 4.7%; V-A, 52.2% +/- 3.9%). This contribution increased to 90% in starved rats, again, with no difference between A-V (95.2% +/- 1.8%) and V-A (89.2% +/- 1.3%) modes. In conclusion, during infusion of [2-13C]glycerol, total GNG measured from MIDA of glucose is independent of the infusion-sampling mode, contrary to calculations of Rt and GNG from glycerol. Measurement of glycerol IE in portal venous blood reconciles the results obtained with the two modes with respect to the contribution of glycerol to GNG. PMID:8692028

  1. The serum levels of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction

    PubMed Central

    Wang, Shu-Jin; Qu, Zhong-Sen; Zhang, Qing-De; Li, Liang; Wang, Feng; Zhang, Bin; Wu, Bang-Li; Zhao, Yu-Wu

    2015-01-01

    To investigate the effect of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction. 112 cases of uremia complicated with cerebral infarction were randomly divided into the peritoneal dialysate with urokinase treatment group (66 cases) and the conventional treatment group (46 cases). At the same time, 50 cases of healthy people who were more than 45 years old were enrolled in the control group. The basic treatment in both treatment groups was the same. In urokinase therapy group based on the conventional treatment, urokinase was added into peritoneal dialysis fluid, and changes of serum MMP-9, MMP-2 and vWF were observed by drawing blood at different time points within 8 weeks. The changes of serum MMP-2, MMP-9 and vWF were detected by enzyme-linked immunosorbent assay. At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2, vWF were significantly higher (P<0.05, P<0.05, P<0.01). Conventional antiplatelet therapy in brain protection only reduce MMP-9 to the normal range (P>0.05) within 8 weeks. But the MMP-2 and vWF cannot be reduced to the normal range (P<0.01, P<0.01). Low doses of urokinase can reduce MMP-9 (7 d) and MMP-2 (14 d) to the normal range (P>0.05, P>0.05) at the early stage and decrease the vWF to a normal range within 8 weeks (P>0.05). At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2 and vWF increased significantly. Low doses of urokinase dialysis can reduce serum MMP-9, MMP-2, and vWF in acute uremia complicated with cerebral infarction without recurrence of cerebral infarction and cerebral hemorrhagic transformation, indicating that low dose of urokinase peritoneal dialysis may have a certain effect on the early treatment of this disease. PMID:26550224

  2. Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor.

    PubMed Central

    Stacey, K J; Fowles, L F; Colman, M S; Ostrowski, M C; Hume, D A

    1995-01-01

    The mouse urokinase-type plasminogen activator (uPA) gene was used as a model macrophage colony-stimulating factor 1 (CSF-1)-inducible gene to investigate CSF-1 signalling pathways. Nuclear run-on analysis showed that induction of uPA mRNA by CSF-1 and phorbol myristate acetate (PMA) was at the transcriptional level in bone marrow-derived macrophages. CSF-1 and PMA synergized strongly in the induction of uPA mRNA, showing that at least some components of CSF-1 action are mediated independently of protein kinase C. Promoter targets of CSF-1 signalling were investigated with NIH 3T3 cells expressing the human CSF-1 receptor (c-fms). uPA mRNA was induced in these cells by treatment with CSF-1, and a PEA3/AP-1 element at -2.4 kb in the uPA promoter was involved in this response. Ets transcription factors can act through PEA3 sequences, and the involvement of Ets factors in the induction of uPA was confirmed by use of a dominant negative Ets-2 factor. Expression of the DNA binding domain of Ets-2 fused to the lacZ gene product prevented CSF-1-mediated induction of uPA mRNA in NIH 3T3 cells expressing the CSF-1 receptor. Examination of ets-2 mRNA expression in macrophages showed that it was also induced synergistically by CSF-1 and PMA. In the macrophage cell line RAW264, the uPA PEA3/AP-1 element mediated a response to both PMA and cotransfected Ets-2. uPA promoter constructs were induced 60- to 130-fold by Ets-2 expression, and the recombinant Ets-2 DNA binding domain was able to bind to the uPA PEA3/AP-1 element. This work is consistent with a proposed pathway for CSF-1 signalling involving sequential activation of fms, ras, and Ets factors. PMID:7760840

  3. Human retinal pigment epithelial lysis of extracellular matrix: functional urokinase plasminogen activator receptor, collagenase, and elastase.

    PubMed Central

    Elner, Susan G

    2002-01-01

    PURPOSE: To show (1) human retinal pigment epithelial (HRPE) expression of functional urokinase plasminogen activator receptor (uPAR; CD87), (2) HRPE secretion of collagenase and elastase, (3) uPAR-dependent HRPE migration, and (4) uPAR expression in diseased human retinal tissue. METHODS: Immunohistochemistry for uPAR was performed on cultured HRPE cells and in sections of human retina. Double-immunofluorescent staining of live human RPE cells with anti-CR3 antibody (CD11b) was performed to demonstrate the physical proximity of this beta 2 integrin with uPAR and determine whether associations were dependent on RPE confluence and polarity. Extracellular proteolysis by HRPE uPAR was evaluated using fluorescent bodipy-BSA and assessed for specificity by plasminogen activator inhibitor-1 (PAI-1) inhibition. The effect of interleukin-1 beta (IL-1 beta) on uPAR expression was assessed. Collagenase and elastase secretion by unstimulated and IL-1-stimulated HRPE cells was measured by 3H-labelled collagen and elastin cleavage. HRPE-associated collagenase was also assessed by cleavage of fluorescent DQ-collagen and inhibited by phenanthroline. Using an extracellular matrix assay, the roles of uPAR and collagenase in HRPE migration were assessed. RESULTS: Immunoreactive uPAR was detected on cultured HRPE cells and increased by IL-1. On elongated, live HRPE cells, uPAR dissociated from CD11b (CR3) and translocated to anterior poles of migrating cells. Extracellular proteolysis was concentrated at sites of uPAR expression and specifically inhibited by PAI-1. Cultured HRPE cells secreted substantial, functional collagenase and elastase. IL-1 upregulated uPAR, collagenase, and elastase activities. Specific inhibition of uPAR, and to a lesser degree collagenase, reduced HRPE migration in matrix/gel assays. Immunoreactive uPAR was present along the HRPE basolateral membrane in retinal sections and in sections of diseased retinal tissue. CONCLUSIONS: HRPE cells express functional u

  4. 21 CFR 526.1590 - Novobiocin infusion.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... strains of Staphylococcus aureus. (iii) Limitations. Do not milk for at least 6 hours after treatment... is used in dry cows for the treatment of mastitis caused by susceptible strains of Staphylococcus aureus and Streptococcus agalactiae. (iii) Limitations. Infuse each quarter at the time of drying...

  5. Multiple Intravenous Infusions Phase 1b

    PubMed Central

    Cassano-Piché, A; Fan, M; Sabovitch, S; Masino, C; Easty, AC

    2012-01-01

    Background Minimal research has been conducted into the potential patient safety issues related to administering multiple intravenous (IV) infusions to a single patient. Previous research has highlighted that there are a number of related safety risks. In Phase 1a of this study, an analysis of 2 national incident-reporting databases (Institute for Safe Medical Practices Canada and United States Food and Drug Administration MAUDE) found that a high percentage of incidents associated with the administration of multiple IV infusions resulted in patient harm. Objectives The primary objectives of Phase 1b of this study were to identify safety issues with the potential to cause patient harm stemming from the administration of multiple IV infusions; and to identify how nurses are being educated on key principles required to safely administer multiple IV infusions. Data Sources and Review Methods A field study was conducted at 12 hospital clinical units (sites) across Ontario, and telephone interviews were conducted with program coordinators or instructors from both the Ontario baccalaureate nursing degree programs and the Ontario postgraduate Critical Care Nursing Certificate programs. Data were analyzed using Rasmussen’s 1997 Risk Management Framework and a Health Care Failure Modes and Effects Analysis. Results Twenty-two primary patient safety issues were identified with the potential to directly cause patient harm. Seventeen of these (critical issues) were categorized into 6 themes. A cause-consequence tree was established to outline all possible contributing factors for each critical issue. Clinical recommendations were identified for immediate distribution to, and implementation by, Ontario hospitals. Future investigation efforts were planned for Phase 2 of the study. Limitations This exploratory field study identifies the potential for errors, but does not describe the direct observation of such errors, except in a few cases where errors were observed. Not all

  6. Infusing Catholic Identity throughout the Campus Community

    ERIC Educational Resources Information Center

    Miller, Amata

    2011-01-01

    This article, originally presented as a plenary address at the Association of Catholic Colleges and Universities 2011 Annual Meeting, addresses a bottom-up methodology for infusing the spirit of Catholic identity more deeply throughout a campus community. The author begins with an exploration of some theoretical underpinnings of this approach and…

  7. Liquid infused surfaces in turbulent channel flow

    NASA Astrophysics Data System (ADS)

    Fu, Matthew; Stone, Howard; Smits, Alexander; Jacobi, Ian; Samaha, Mohamed; Wexler, Jason; Shang, Jessica; Rosenberg, Brian; Hellström, Leo; Fan, Yuyang; Wang, Karen; Lee, Kevin; Hultmark, Marcus

    2014-11-01

    A turbulent channel flow facility is used to measure the drag reduction capabilities and dynamic behavior of liquid-infused micro-patterned surfaces. Liquid infused surfaces have been proposed as a robust alternative to traditional air-cushion-based superhydrophobic surfaces. The mobile liquid lubricant creates a surface slip with the outer turbulent shear flow as well as an energetic sink to dampen turbulent fluctuations. Micro-manufactured surfaces can be mounted flush in the channel and exposed to turbulent flows. Two configurations are possible, both capable of producing laminar and turbulent flows. The first configuration allows detailed investigation of the infused liquid layer and the other allows well resolved pressure gradient measurements. Both of the configurations have high aspect ratios 15-45:1. Drag reduction for a variety of liquid-infused surface architectures is quantified by measuring pressure drop in the channel. Flow in the oil film is simultaneously visualized using fluorescent dye. Supported under ONR Grants N00014-12-1-0875 and N00014-12-1-0962 (program manager Ki-Han Kim).

  8. A Telecommunications-Infused Community Action Project.

    ERIC Educational Resources Information Center

    March, Thomas; Puma, Jessica

    1996-01-01

    The Nonprofit Prophets, a telecommunications-infused community action project, was designed for high school students. Students were teamed with a nonprofit organization and produced videoconferences or Web sites for them. Although specific skills were acquired, students also gained confidence and self-esteem as well as a belief that they…

  9. The NASA SARP Software Research Infusion Initiative

    NASA Technical Reports Server (NTRS)

    Hinchey, Mike; Pressburger, Tom; Markosian, Lawrence; Feather, Martin

    2006-01-01

    A viewgraph presentation describing the NASA Software Assurance Research Program (SARP) research infusion projects is shown. The topics include: 1) Background/Motivation; 2) Proposal Solicitation Process; 3) Proposal Evaluation Process; 4) Overview of Some Projects to Date; and 5) Lessons Learned.

  10. Infusing interprofessional education into the nursing curriculum.

    PubMed

    Cranford, Joan Sistrunk; Bates, Teresa

    2015-01-01

    Education for interprofessional collaboration should begin early in the nursing program with a gradual infusion of interprofessional competencies into the curriculum. The faculty developed an interprofessional education program for students in nursing, physical therapy, nutrition, and respiratory care, which focused on sharing knowledge about each discipline, developing respect and value for each other's disciplines, and emphasizing techniques to improve communication and teamwork.

  11. Effect of an additional atropine injection during dobutamine infusion for myocardial SPET.

    PubMed

    Caner, B; Karanfil, A; Uysal, U; Tokgozoglu, L; Aksoyek, S; Ugur, O; Ciftci, I; Atalar, E; Kes, S; Bekdik, C

    1997-06-01

    The aim of this study was to examine the value of an additional atropine injection in patients who do not achieve an adequate heart rate during dobutamine infusion for myocardial perfusion SPET (single photon emission tomography). Patients undergoing dobutamine myocardial SPET who failed to achieve > or = 85% of their age-predicted maximal heart rate at the end of dobutamine infusion (D protocol) had a second dobutamine myocardial SPET study on a separate day with the addition of an atropine injection during the dobutamine infusion (D + A protocol). Twenty-nine patients were studied. 201Tl was used in 27 patients and 99Tc(m)-MIBI in two patients. All patients underwent coronary angiography and significant coronary artery disease was found in 19 of 29 patients. The mean heart rate obtained at the peak of dobutamine infusion in the D + A protocol was significantly higher than that in the D protocol (153.8 +/- 13.8 vs 117.5 +/- 15.3 beats min[-1]). The D + A protocol resulted in a higher diagnostic sensitivity for the detection of stenosed coronaries compared with the D protocol (87 vs 80%, P > 0.05) without changing the specificity (89% for both protocols). On the other hand, the frequency of side-effects and ECG changes during the D + A protocol was higher than that with the D protocol (32 vs 47). In conclusion, the addition of an atropine injection during dobutamine infusion resulted in a higher diagnostic sensitivity for identifying stenosed coronaries compared to dobutamine alone.

  12. Fentanyl infusion anesthesia for aortocoronary bypass surgery: plasma levels and hemodynamic response.

    PubMed

    Sprigge, J S; Wynands, J E; Whalley, D G; Bevan, D R; Townsend, G E; Nathan, H; Patel, Y C; Srikant, C B

    1982-12-01

    Plasma fentanyl concentrations were measured by radioimmunoassay in patients during aortocoronary bypass surgery and correlated with hemodynamic responses to surgical stimulation. Thirty patients scheduled for aortocoronary bypass surgery were divided into three groups of 10. Patients in group 1 received fentanyl, 30 micrograms/kg, as a loading dose followed by an infusion of 0.3 microgram/kg/min; those in group 2 received 40 micrograms/kg as a loading dose followed by an infusion of 0.4 microgram/kg/min; and those in group 3 received 50 micrograms/kg as the loading dose followed by an infusion of 0.5 microgram/kg/min. The total dose of fentanyl administered to each group up to the time of rewarming on cardiopulmonary bypass was 60 micrograms/kg, 90 micrograms/kg, respectively. Each of the dose regimens produced stable plasma concentrations starting approximately 20 minutes after induction and continuing until the infusion was discontinued. Patients in group 1 had a mean plasma concentration of 10 to 12 ng/ml in the stable period compared with 12 to 14 ng/ml in group 2 and 15 to 18 ng/ml in group 3. Fewer patients in group 3 responded to intubation and surgical stimulation than in the other groups, although the differences between groups were not statistically significant. Response to stimulation was treated by the administration of droperidol or volatile anesthetic agents. At a plasma concentration of 15 ng/ml, 50% of patients had an increase in systolic blood pressure which required treatment. This minimal intra-arterial concentration, analogous to MAC, can be achieved by the administration of fentanyl as a loading dose of 50 micrograms/kg followed by an infusion of 0.5 microgram/kg/min.

  13. Hardening of the arteries

    MedlinePlus

    Atherosclerosis; Arteriosclerosis; Plaque buildup - arteries; Hyperlipidemia - atherosclerosis; Cholesterol - atherosclerosis ... Hardening of the arteries often occurs with aging. As you grow older, ... narrows your arteries and makes them stiffer. These changes ...

  14. Peripheral arterial line (image)

    MedlinePlus

    A peripheral arterial line is a small, short plastic catheter placed through the skin into an artery of the arm or leg. The purpose of a peripheral arterial line is to allow continuous monitoring of ...

  15. Carotid Artery Disease

    MedlinePlus

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  16. Coronary artery disease

    MedlinePlus Videos and Cool Tools

    The coronary arteries supply blood to the heart muscle itself. Damage to or blockage of a coronary artery can result in injury to the heart. Normally, blood flows through a coronary artery unimpeded. However, a ...

  17. Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

    PubMed

    Gabriel, Janice

    2014-11-01

    Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set. PMID:25426880

  18. S-nitrosothiols dilate the mesenteric artery more potently than the femoral artery by a cGMP and L-type calcium channel-dependent mechanism.

    PubMed

    Liu, Taiming; Schroeder, Hobe J; Zhang, Meijuan; Wilson, Sean M; Terry, Michael H; Longo, Lawrence D; Power, Gordon G; Blood, Arlin B

    2016-08-31

    S-nitrosothiols (SNOs) are metabolites of NO with potent vasodilatory activity. Our previous studies in sheep indicated that intra-arterially infused SNOs dilate the mesenteric vasculature more than the femoral vasculature. We hypothesized that the mesenteric artery is more responsive to SNO-mediated vasodilation, and investigated various steps along the NO/cGMP pathway to determine the mechanism for this difference. In anesthetized adult sheep, we monitored the conductance of mesenteric and femoral arteries during infusion of S-nitroso-l-cysteine (L-cysNO), and found mesenteric vascular conductance increased (137 ± 3%) significantly more than femoral conductance (26 ± 25%). Similar results were found in wire myography studies of isolated sheep mesenteric and femoral arteries. Vasodilation by SNOs was attenuated in both vessel types by the presence of ODQ (sGC inhibitor), and both YC-1 (sGC agonist) and 8-Br-cGMP (cGMP analog) mediated more potent relaxation in mesenteric arteries than femoral arteries. The vasodilatory difference between mesenteric and femoral arteries was eliminated by antagonists of either protein kinase G or L-type Ca(2+) channels. Western immunoblots showed a larger L-type Ca(2+)/sGC abundance ratio in mesenteric arteries than in femoral arteries. Fetal sheep mesenteric arteries were more responsive to SNOs than adult mesenteric arteries, and had a greater L-Ca(2+)/sGC ratio (p = 0.047 and r = -0.906 for correlation between Emax and L-Ca(2+)/sGC). These results suggest that mesenteric arteries, especially those in fetus, are more responsive to SNO-mediated vasodilation than femoral arteries due to a greater role of the L-type calcium channel in the NO/cGMP pathway.

  19. Technology Infusion and Higher Education: Changing Teaching and Learning.

    ERIC Educational Resources Information Center

    Miller, John W.; Martineau, Leonard P.; Clark, Robert C.

    2000-01-01

    Discussion of technology infusion in higher education focuses on whether such infusion is necessary, on barriers to more rapid expansion of technology assisted learning (both organizational barriers and individual resistance), and on changes needed to speed infusion, including changes at the system level and those to be made by individual faculty.…

  20. 40 CFR 721.10287 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10287 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-11-188) is subject to reporting under this section for...

  1. 40 CFR 721.10287 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10287 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-11-188) is subject to reporting under this section for...

  2. 40 CFR 721.10706 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10706 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-12-576) is subject to reporting under this section for...

  3. 40 CFR 721.10287 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10287 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-11-188) is subject to reporting under this section for...

  4. 75 FR 21641 - Infusion Pumps; Public Meeting; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... HUMAN SERVICES Food and Drug Administration Infusion Pumps; Public Meeting; Request for Comments AGENCY... Food and Drug Administration (FDA) is announcing a public meeting regarding external infusion pumps... infusion pump use, to help the agency identify quality assurance strategies to mitigate these problems,...

  5. [Portable elastomeric infusion system applied to patients with knee prosthesis].

    PubMed

    Soler, Gemma; Quiles, Olga; Nicolau, Agnes; Faura, Teresa; Moreno, Cristina

    2007-03-01

    An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion. PMID:17474369

  6. Career Education Infused into the Social Studies Curriculum.

    ERIC Educational Resources Information Center

    Hudson, Patricia; Griggs, Shirley A.

    Social studies teachers can help students develop self- and career awareness by infusing career education into the social studies curriculum. The infusion method of career education is preferred since it can make the content of lessons more relevant for students. In addition, infusion of career education is particularly appropriate in social…

  7. Improvement of the microcirculation in the acute ischemic rat limb during intravenous infusion of drag-reducing polymers.

    PubMed

    Hu, Feng; Zha, Daogang; Du, Rongsheng; Chen, Xianghui; Zhou, Bingjie; Xiu, Jiancheng; Bin, Jianping; Liu, Yili

    2011-01-01

    Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study is to examine the effects of DRPs on microcirculation in rat hind limb during acute femoral artery occlusion. Two groups of 20 male Wistar rats were subjected to either hemodynamic measurement or contrast enhanced ultrasound (CEU) imaging during peripheral ischemia. Both groups were further subdivided into a DRP-treated group or a saline-treated group. Polyethylene oxide (PEO) was chosen as the test DRP, and rats were injected with either 10 ppm PEO solution or saline through the caudal vein at a constant rate of 5 ml/h for 20 min. Abdominal aortic flow, iliac artery pressure, iliac vein pressure, heart rate, carotid artery pressure and central venous pressure (CVP) were monitored, and vascular resistance was calculated by (iliac artery pressure-iliac vein pressure)/abdominal aortic blood flow. Flow perfusion and capillary volume of skeletal muscle were measured by CEU. During PEO infusion, abdominal aortic blood flow increased (p<0.001) and vascular resistance decreased (p<0.001) compared to rats that received saline during peripheral ischemia. There was no significant change in ischemic skeletal capillary volume (A) with DRP treatment (p>0.05), but red blood cell velocity (β) and capillary blood flow (A×β) increased significantly (p<0.05) during PEO infusion. In addition, A, β and A×β all increased (p<0.05) in the contralateral hind limb muscle. In contrast, PEO had no significant influence on heart rate, mean carotid artery blood pressure or CVP. Intravenous infusion of drag reducing polymers may offer a novel hydrodynamic approach for improving microcirculation during acute peripheral ischemia.

  8. Haemodynamic interactions of medetomidine and the peripheral alpha-2 antagonist MK-467 during step infusions in isoflurane-anaesthetised dogs.

    PubMed

    Kaartinen, Johanna; del Castillo, Jérôme R E; Salla, Kati; Troncy, Eric; Raekallio, Marja R; Vainio, Outi M

    2014-11-01

    The haemodynamic interactions of a step infusion with medetomidine (MED) and the peripherally acting alpha-2 antagonist MK-467 (MK) were compared with MED infused alone in isoflurane-anaesthetised dogs. Eight purposely-bred Beagles were used in a randomised crossover study. Anaesthesia was induced with propofol intravenously (IV) and maintained with isoflurane in oxygen. Dogs received 1.25 µg/kg MED as a 1 min loading dose IV, along with a step-down MED infusion at rates of 8.0 µg/kg/h (step 1: 0-20 min), 5.5 µg/kg/h (step 2: 20-40 min) and 4.0 µg/kg/h (step 3: 40-95 min). Five minutes after starting the MED infusion, the dogs received MK-467 in a step-up infusion at rates of 100 µg/kg/h (step 1: 5-35 min), 200 µg/kg/h (step 2: 35-65 min) and 500 µg/kg/h (step 3: 65-95 min). Heart rate (HR), systolic (SAP) and mean arterial (MAP) blood pressures and arteriovenous oxygen content differences (a-vO2 diff) were calculated. Plasma drug concentrations were analysed. Repeated-measures general linear mixed models with Bonferroni correction were used for statistical analyses. MED infusion alone increased SAP maximally by 24.9%, MAP by 34.7% and a-vO2 diff by 222.5%, and reduced HR by 32.3%, but these changes were significantly attenuated by MK-467. Most MED effects returned to baseline during step 2 of MK-467 infusion and step 3 of MED infusion (MED/MK-467 ratio 1:18 to 1:50). Plasma concentrations of MED tended to be lower with the addition of MK-467. The use of step infusions helped to narrow down the therapeutic range for the MED/MK-467 infusion dose ratio during isoflurane anaesthesia in dogs.

  9. Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha.

    PubMed

    Agaphonov, Michael; Romanova, Nina; Sokolov, Sviatoslav; Iline, Anna; Kalebina, Tatyana; Gellissen, Gerd; Ter-Avanesyan, Michael

    2005-11-01

    Human urokinase-type plasminogen activator (uPA) is poorly secreted by yeast cells. Here, we have selected Hansenula polymorpha mutants with increased productivity of active extracellular uPA. Several of the obtained mutants also demonstrated a defect of sorting of carboxypeptidase Y to the vacuole and the mutant loci have been identified in six of them. All these mutations damaged genes involved in protein traffic between the Golgi apparatus and the vacuole, namely PEP3, VPS8, VPS10, VPS17, and VPS35. We have shown that inactivation of the VPS10 gene encoding the vacuolar protein sorting receptor does not increase uPA secretion but stimulates its proteolytic processing. PMID:16181812

  10. A proposal of potent inhibitor for cancer metastasis blocking the pocket of urokinase receptor: ab initio molecular simulations

    NASA Astrophysics Data System (ADS)

    Kasumi, Tomoyo; Araki, Kohta; Mizushima, Tatsuroh; Kobayashi, Hiroshi; Kurita, Noriyuki

    2013-04-01

    Recent biochemical experiments have elucidated that a variety of proteases play important roles in cancer invasion and metastasis. In particular, binding of urokinase-type plasminogen activator (uPA) to uPA receptor (uPAR) existing on the surface of a cancer cell is considered to be a trigger for cancer invasions. Therefore, the blocking of the binding is expected to inhibit cancer invasion. In previous experiments, several peptides of amino acids were proposed as a potent inhibitor for blocking the binding. In the present study, we obtained stable structures of the solvated complexes with uPAR and the peptides and investigated the specific interactions between uPAR and the peptides by ab initio molecular simulations. Base on these results, we clarified which peptide can bind more strongly to uPAR and proposed a novel potent peptide which can inhibit the uPAR-uPA binding efficiently.

  11. Impact of priming the infusion system on the performance of target-controlled infusion of remifentanil

    PubMed Central

    Kim, Jong-Yeop; Moon, Bong-Ki; Lee, Jong Hyuk; Jo, Youn Yi

    2013-01-01

    Background The start-up behavior of syringe and syringe pump is known to be one of the causes of inaccurate intravenous infusion. This study evaluated the method of priming the infusion system (PRIMING), and its impact on the target-controlled infusion (TCI) of two remifentanil diluents. Methods PRIMING was performed using an evacuation of 2.0 ml to the atmosphere prior to TCI. Forty-eight TCI, using 50 µg/ml (Remi50) or 20 µg/ml (Remi20) of diluents, were performed targeting 4.0 ng/ml of effect-site concentration (Ceff), with PRIMING or not. The gravimetrical measurements of the delivered infusates reproduced actual Ceff. The bolus amount and time to reach 95% target were compared. Results Without PRIMING, Remi50 infused less bolus (43 ± 23 %) than Remi20 (19 ± 9 %) (P = 0.003), and showed more delayed increase of Ceff (11.2 ± 4.0 min) than Remi20 (7.4 ± 0.4 min) (P = 0.028). However, PRIMING significantly decreased the deficit of the bolus (2 ± 1%), as well as the delay of the increase of Ceff in Remi50 (1.2 ± 0.2 min) (both P < 0.001). In addition, with PRIMING, the start-up bolus showed minimal difference to the nominal bolus (1 and 2%), and Ceff were increased to 4.0 ± 0.1 ng/ml at the expected time of peak effect, irrespective of the diluents. Conclusions Proper operation of the syringe pump used in the priming of the syringe may be helpful in reduction of the inaccuracy of TCI, particularly during the early phase of infusion, or the infusion of a more concentrated diluent. PMID:23741562

  12. Mouse intragastric infusion (iG) model

    PubMed Central

    Ueno, Akiko; Lazaro, Raul; Wang, Ping-Yen; Higashiyama, Reiichi; Machida, Keigo; Tsukamoto, Hidekazu

    2014-01-01

    Direct intragastric delivery of a diet, nutrient or test substance can be achieved in rodents (mice and rats) on a long-term (2–3 months) basis using a chronically implanted gastrostomy catheter and a flow-through swivel system. This rodent intragastric infusion (iG) model has broad applications in research on food intake, gastrointestinal (GI) physiology, GI neuroendocrinology, drug metabolism and toxicity, obesity and liver disease. It achieves maximal control over the rate and pattern of delivery and it can be combined with normal ad libitum feeding of solid diet if so desired. It may be adopted to achieve infusion at other sites of the GI system to test the role of a bypassed GI segment in neuroendocrine physiology, and its use in genetic mouse models facilitates the genetic analysis of a central question under investigation. PMID:22461066

  13. Software Engineering Technology Infusion Within NASA

    NASA Technical Reports Server (NTRS)

    Zelkowitz, Marvin V.

    1996-01-01

    Abstract technology transfer is of crucial concern to both government and industry today. In this paper, several software engineering technologies used within NASA are studied, and the mechanisms, schedules, and efforts at transferring these technologies are investigated. The goals of this study are: 1) to understand the difference between technology transfer (the adoption of a new method by large segments of an industry) as an industry-wide phenomenon and the adoption of a new technology by an individual organization (called technology infusion); and 2) to see if software engineering technology transfer differs from other engineering disciplines. While there is great interest today in developing technology transfer models for industry, it is the technology infusion process that actually causes changes in the current state of the practice.

  14. Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis

    PubMed Central

    2014-01-01

    Background Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. Recent studies have proposed that plasma soluble urokinase receptor (suPAR) might be a causative circulating factor but this proposal has caused controversy. This study aimed to measure urinary suPAR levels in patients with primary FSGS and its significance in the pathogenesis of FSGS. Methods Sixty-two patients with primary FSGS, diagnosed between January 2006 and January 2012, with complete clinical and pathologic data were enrolled, together with disease and normal controls. Urinary suPAR levels were measured using commercial ELISA kits and were corrected by urinary creatinine (Cr). The associations between urinary suPAR levels and clinical data at presentation and during follow up were analyzed. Conditionally immortalized human podocytes were used to study the effect of urinary suPAR on activating β3 integrin detected by AP5 staining. Results The urinary suPAR level of patients with primary FSGS (500.56, IQR 262.78 to 1,059.44 pg/μmol Cr) was significantly higher than that of patients with minimal change disease (307.86, IQR 216.54 to 480.18 pg/μmol Cr, P = 0.033), membranous nephropathy (250.23, IQR 170.37 to 357.59 pg/μmol Cr, P <0.001), secondary FSGS (220.45, IQR 149.38 to 335.54 pg/μmol Cr, P <0.001) and normal subjects (183.59, IQR 103.92 to 228.78 pg/μmol Cr, P <0.001). The urinary suPAR level of patients with cellular variant was significantly higher than that of patients with tip variant. The urinary suPAR level in the patients with primary FSGS was positively correlated with 24-hour urine protein (r = 0.287, P = 0.024). During follow up, the urinary suPAR level of patients with complete remission decreased significantly (661.19, IQR 224.32 to 1,115.29 pg/μmol Cr versus 217.68, IQR 121.77 to 415.55 pg/μmol Cr, P = 0.017). The AP5 signal was strongly induced along the cell membrane when human differentiated podocytes were incubated

  15. A Mouse Model of Inducible Liver Injury Caused by Tet-On Regulated Urokinase for Studies of Hepatocyte Transplantation

    PubMed Central

    Song, Xijun; Guo, Yushan; Duo, Shuguang; Che, Jie; Wu, Chen; Ochiya, Takahiro; Ding, Mingxiao; Deng, Hongkui

    2009-01-01

    Mouse models of liver injury provide useful tools for studying hepatocyte engraftment and proliferation. A representative model of liver injury is the albumin-urokinase (Alb-uPA) transgenic model, but neonatal lethality hampers its widespread application. To overcome this problem, we generated a transgenic mouse in which transcription of the reverse tetracycline transactivator was (rtTA) driven by the mouse albumin promoter, and backcrossed the rtTA mice onto severe combined immunodeficient (SCID)/bg mice to generate immunodeficient rtTA/SCID mice. We then produced recombinant adenoviruses Ad.TRE-uPA, in which the urokinase was located downstream of the tetracycline response element (TRE). The rtTA/SCID mouse hepatocytes were then infected with Ad.TRE-uPA to establish an inducible liver injury mouse model. In the presence of doxycycline, uPA was exclusively expressed in endogenous hepatocytes and caused extensive liver injury. Enhanced green fluorescent protein-labeled mouse hepatocytes selectively repopulated the rtTA/SCID mouse liver and replaced over 80% of the recipient liver mass after repeated administration of Ad.TRE-uPA. Compared with the original uPA mice, rtTA/SCID mice did not exhibit problems regarding breeding efficiency, and the time window for transplantation was flexible. In addition, we could control the extent of liver injury to facilitate transplantation surgery by regulating the dose of Ad.TRE-uPA. Our inducible mouse model will be convenient for studies of hepatocyte transplantation and hepatic regeneration, and this system will facilitate screening for potential genetic factors critical for engraftment and proliferation of hepatocytes in vivo. PMID:19808649

  16. Insulin infusion therapy in critically ill patients.

    PubMed

    Boutin, Jean-Marie; Gauthier, Lyne

    2014-04-01

    While dysglycemia (hyperglycemia, hypoglycemia and glucose variability) is clearly associated with increased mortality in critically ill patients, target range of blood glucose control remains controversial. Standardized insulin infusion protocols constitute the basis of treatment of these patients. The choice of protocol and its implementation is a great challenge. In this article, we review the published data to help define the essential elements that compose a good protocol and apply the right conditions to make it safe and effective. PMID:24690510

  17. Mathematical Modelling of the Infusion Test

    NASA Astrophysics Data System (ADS)

    Cieslicki, Krzysztof

    2007-01-01

    The objective of this paper was to improve the well established in clinical practice Marmarou model for intracranial volume-pressure compensation by adding the pulsatile components. It was demonstrated that complicated pulsation and growth in intracranial pressure during infusion test could be successfully modeled by the relatively simple analytical expression derived in this paper. The CSF dynamics were tested in 25 patients with clinical symptoms of hydrocephalus. Basing on the frequency spectrum of the patient's baseline pressure and identified parameters of CSF dynamic, for each patient an "ideal" infusion test curve free from artefacts and slow waves was simulated. The degree of correlation between simulated and real curves obtained from clinical observations gave insight into the adequacy of assumptions of Marmarou model. The proposed method of infusion tests analysis designates more exactly the value of the reference pressure, which is usually treated as a secondary and of uncertain significance. The properly identified value of the reference pressure decides on the degree of pulsation amplitude growth during IT, as well as on the value of elastance coefficient. The artificially generated tests with various pulsation components were also applied to examine the correctness of the used algorithm of identification of the original Marmarou model parameters.

  18. Light protection of chemotherapy drugs for infusion.

    PubMed

    Clarkson, Douglas McG; Harvey, Roger; Sheepy, Dave

    2015-02-01

    Specific chemotherapy drugs which require to be delivered by continuous infusion over time can have their effectiveness impaired by exposure to optical radiation. Mechanisms and processes of drug preparation and patient administration associated with light sensitive drugs were monitored within a Chemotherapy Unit. Levels of ambient light at locations of drug preparation/administration and levels of protection afforded by optical filter elements such as infusion lines were determined using a double grating Bentham Dmc150 spectroradiometer. Models of light exposure were developed for separate components of drug preparation and infusion delivery systems where the latter included the fluid bag with protective light cover, drip chamber and giving set line. In addition, the attenuation coefficient of Dacarbazine at the concentration typically used in patient treatments was determined using specially manufactured measurement cells. The relative contributions to light absorption of the drug bag, drip chamber and patient line were identified for specific types of giving sets, spectral content/intensity of light exposure and specific drug light absorption profiles. This indicated significant differences in the level of light protection afforded by specific giving sets and either single or double layer protection of the drug bag reservoir. It is not clear, however, if these variations could lead to significant differences of levels of drug de-activation and/or creation of undesirable photo-products such as in the case of Dacarbazine. Such techniques, however, provide a means of identifying how light exposure can be maintained at levels as low as reasonably possible as a precautionary measure.

  19. Irreversible sediment formation in green tea infusions.

    PubMed

    Xu, Yong-Quan; Chen, Gen-Sheng; Wang, Qiu-Shuang; Yuan, Hai-Bo; Feng, Chun-Hong; Yin, Jun-Feng

    2012-03-01

    The formation of irreversible tea sediment (IRS) and its chemical components in green tea infusions were investigated. The results showed that the amounts of IRS in the green tea infusions from various tea cultivars ranged from 0.10 to 1.47 mg/mL. The amount of IRS was influenced remarkably by the chemical components in the green tea infusion. Principal component analysis and regression analysis indicated that gallated catechins, Mn, Ca, caffeine, Na, and (-)-gallocatechin gallate (GCG) were the principal components. IRS (mg/mL) = -4.226 + 0.275 gallated catechins + 79.551 Na + 7.321 Mn + 21.055 Ca + 0.513 caffeine - 0.129 GCG (R2 = 0.697). The contents of the main chemical components in the reversible tea sediment (RTS) and IRS were markedly different, especially the minerals. Large amount of minerals participated in the formation of irreversible green tea sediment. The amount of IRS increased with the extraction temperature. PMID:22329921

  20. Nonstationary disposition of valproic acid during prolonged intravenous infusion: contributions of unbound clearance and protein binding.

    PubMed

    Arens, T L; Pollack, G M

    2001-09-01

    Circadian variations in disposition have been observed for a variety of agents, including anticonvulsants. Valproic acid (VPA), an anticonvulsant used to control generalized and partial seizures, has exhibited diurnal oscillations in steady-state concentrations during long-term administration to humans and non-human primates. The present study was conducted to assess potential diurnal changes in the disposition of VPA during prolonged i.v. infusion in rats. Animals, maintained on a strict 12-h per day light cycle, were equipped with venous cannulae and an arterial microdialysis probe. VPA was administered as a 50-mg/kg loading dose followed by a 42 mg/kg/h infusion for 70 h. Blood and microdialysate samples were obtained at timed intervals after establishment of steady-state throughout two complete light/dark cycles; and total (serum) and unbound (microdialysate) VPA was determined by gas chromatography. Modest oscillations (6-7 h period) in total and unbound VPA were observed; clearance and binding parameters were not different between light and dark periods. However, unbound clearance increased, and unbound fraction decreased, with time over the course of the infusion. These results suggest that time-dependent changes in VPA disposition occur in rats, although oscillations in steady-state concentrations do not appear to be diurnal in nature. PMID:11754040

  1. Pharmacokinetics of sufentanil during long-term infusion in critically ill pediatric patients.

    PubMed

    Bartkowska-Śniatkowska, Alicja; Bienert, Agnieszka; Wiczling, Paweł; Rosada-Kurasińska, Jowita; Zielińska, Marzena; Warzybok, Justyna; Borsuk, Agnieszka; Tibboel, Dick; Kaliszan, Roman; Grześkowiak, Edmund

    2016-01-01

    The aim of this study was to develop a population pharmacokinetic model of sufentanil and to assess the influence of covariates in critically ill children admitted to a pediatric intensive care unit. After institutional approval, 41 children were enrolled in the study. Blood samples for pharmacokinetic (PK) assessment were collected from routinely placed arterial catheters during and after discontinuation of infusion. Population nonlinear mixed-effects modeling was performed using NONMEM. A 2-compartment model described sufentanil PK sufficiently. Typical values of the central and peripheral volume of distribution and the metabolic and intercompartmental clearance for a theoretical patient weighing 70 kg were VC = 7.90 l, VT  = 481 L, Cl =  5.3 L/h, and Q = 38.3 L/h, respectively. High interindividual variability of all PK parameters was noted. Allometric/isometric principles to scale sufentanil PK revealed that to achieve the same steady-state sufentanil concentrations in plasma for pediatric patients of different body weights, the infusion rate should follow the formula (infusion rate for a 70-kg adult patient, μg/h) × (body weight/70 kg)(0.75). Severity of illness described by PRISM score, the monitored physiological and laboratory parameters, and coadministered drugs such as vasopressors were not found to be significant covariates.

  2. Atrial natriuretic peptide increases microvascular blood flow and macromolecular escape during renin infusion in the hamster

    SciTech Connect

    Boric, M.P.; Albertini, R. )

    1990-02-01

    The effects of Atrial Natriuretic Peptide (ANP) on microvascular hemodynamics and macromolecular permselectivity were studied in the hamster cheek pouch under resting conditions and during intravenous renin infusion. Fluorescent intravital microscopy was used to observe arteriolar diameters and to detect escape of fluorescent dextran of 150 K-Daltons (FITC-Dx-150). Microvascular plasma flow was estimated by clearance of 51Cr-EDTA and net macromolecular transport by clearance of FITC-Dx-150. At rest, topical ANP (2-250 ng/ml) had no effect on arteriolar diameter, 51Cr-EDTA clearance, relative vascular conductance (RVC) or FITC-Dx-150 clearance. Infusion of renin (10 mU/Kg/Hr, iv) elevated systemic arterial pressure by 30% and reduced cheek pouch RVC by 26%. During renin infusion, topical ANP (50 ng/ml) produced transient arteriolar vasodilation, and increased 51Cr-EDTA clearance (+35%), RVC (+58%) and FITC-Dx-150 clearance (+54%), without affecting systemic pressure. ANP did not induce venular leakage sites under any condition, but changes in FITC-Dx-150 clearance were highly correlated with changes in 51Cr-EDTA clearance, suggesting that the larger macromolecular escape was due to increases in microvascular blood flow and capillary/post-capillary hydrostatic pressure.

  3. Modification by choline of adrenergic transmission in rat mesenteric arteries

    PubMed Central

    Malik, K. U.; McGiff, J. C.

    1971-01-01

    1. The action of choline on the vasoconstrictor responses of the perfused mesenteric arteries of the rat to sympathetic nerve stimulation and to injected noradrenaline has been investigated. 2. The infusion of choline (500 μg/ml), for periods of 15 s, increased the response to sympathetic nerve stimulation, whereas the infusion of the same concentration for 20 min greatly reduced the response to nerve stimulation. Choline (up to 500 μg/ml), infused either for short or long periods, did not alter the response to injected noradrenaline. 3. The inhibitory action of choline on the response to nerve stimulation was abolished either by an increase in the calcium concentration from 1·8 to 5·4 mM or by simultaneous infusion of (+)-amphetamine or atropine. 4. The results suggest that choline in concentrations of 500 μg/ml has the same effect on adrenergic transmission in mesenteric arteries as acetylcholine at concentrations of 5 ng/ml. PMID:4339884

  4. Total i.v. anaesthesia with propofol and alfentanil for coronary artery bypass grafting.

    PubMed

    Manara, A R; Monk, C R; Bolsin, S N; Prys-Roberts, C

    1991-06-01

    The haemodynamic effects of total i.v. anaesthesia with a combination of propofol and alfentanil infusions were studied in eight patients with good left ventricular function undergoing coronary artery bypass surgery. Haemodynamic indices were measured before anaesthesia and at specified intervals before cardiopulmonary bypass. The technique resulted in haemodynamic changes comparable to those reported with opioid-based anaesthesia for coronary artery surgery, and has potential advantages. PMID:2064887

  5. Hemodynamic effects of 6% hydroxyethyl starch infusion in sevoflurane-anesthetized thoroughbred horses.

    PubMed

    Ohta, Minoru; Kurimoto, Shinjiro; Tokushige, Hirotaka; Kuroda, Taisuke; Ishikawa, Yuhiro

    2013-07-31

    To determine hemodynamic effects of hydroxyethyl starch (HES) infusion during anesthesia in horses, incremental doses of 6% HES were administered to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and administered 3 intravenous dose of 6% HES (5 ml/kg) over 15 min with 15-min intervals in addition to constant infusion of lactated Ringer's solution at 10 ml/kg/hr. Hemodynamic parameters were measured before and every 15 min until 90 min after the administration of 6% HES. There was no significant change in heart rate and arterial blood pressures throughout the experiment. The HES administration produced significant increases in mean right atrial pressure, stroke volume, cardiac output (CO) and decrease in systemic vascular resistance (SVR) in a dose-dependent manner. There was no significant change in electrolytes (Na(+), K(+), Cl(-)) throughout the experiment, however, packed cell volume, hemoglobin concentration, and total protein and albumin concentrations decreased in a dose-dependent manner following the HES administration. In conclusion, the HES administration provides a dose-dependent increase in CO, but has no impact upon arterial blood pressures due to a simultaneous decrease in SVR. PMID:23411483

  6. Cardiopulmonary Effects of Constant-Rate Infusion of Lidocaine for Anesthesia during Abdominal Surgery in Goats.

    PubMed

    Malavasi, Lais M; Greene, Stephen A; Gay, John M; Grubb, Tammy L

    2016-01-01

    Lidocaine is commonly used in ruminants but has an anecdotal history of being toxic to goats. To evaluate lidocaine's effects on selected cardiopulmonary parameters. Isoflurane-anesthetized adult goats (n = 24) undergoing abdominal surgery received a loading dose of lidocaine (2.5 mg/kg) over 20 min followed by constant-rate infusion of lidocaine (100 μg/kg/min); control animals received saline instead of lidocaine. Data collected at predetermined time points during the 60-min surgery included heart rate, mean arterial blood pressure, pO2, and pCO2. According to Welch 2-sample t tests, cardiopulmonary variables did not differ between groups. For example, after administration of the loading dose, goats in the lidocaine group had a mean heart rate of 88 ± 28 bpm, mean arterial blood pressure of 70 ± 19 mm Hg, pCO2 of 65 ± 13 mm Hg, and pO2 of 212 ± 99 mm Hg; in the saline group, these values were 90 ± 16 bpm, 76 ± 12 mm Hg, 61 ± 9 mm Hg, and 209 ± 83 mm Hg, respectively. One goat in the saline group required an additional dose of butorphanol. Overall our findings indicate that, at the dose provided, intravenous lidocaine did not cause adverse cardiopulmonary effects in adult goats undergoing abdominal surgery. Adding lidocaine infusion during general anesthesia is an option for enhancing transoperative analgesia in goats. PMID:27423150

  7. Accuracy of different oxygenation indices in estimating intrapulmonary shunting at increasing infusion rates of dobutamine in horses under general anaesthesia.

    PubMed

    Briganti, A; Portela, D A; Grasso, S; Sgorbini, M; Tayari, H; Bassini, J R Fusar; Vitale, V; Romano, M S; Crovace, A; Breghi, G; Staffieri, F

    2015-06-01

    The aim of this study was to evaluate the correlation of commonly used oxygenation indices with venous admixture (Qs/Qt) in anaesthetised horses under different infusion rates of dobutamine. Six female horses were anaesthetised with acepromazine, xylazine, diazepam, ketamine, and isoflurane, and then intubated and mechanically ventilated with 100% O2. A Swan-Ganz catheter was introduced into the left jugular vein and its tip advanced into the pulmonary artery. Horses received different standardised rates of dobutamine. For each horse, eight samples of arterial and mixed venous blood were simultaneously obtained at fixed times. Arterial and venous haemoglobin (Hb) concentration and O2 saturation, arterial oxygen partial pressure (PaO2), venous oxygen partial pressure (PvO2), and barometric pressure were measured. Arterial (CaO2), mixed venous (CvO2), and capillary (Cc'O2) oxygen contents were calculated using standard formulae. The correlations between F-shunt, arterial oxygen tension to fraction of inspired oxygen ratio (PaO2/FiO2), arterial to alveolar oxygen tension ratio (PaO2/PAO2), alveolar to arterial oxygen tension difference (P[A - a]O2), and respiratory index (P[A - a]O2/PaO2) were tested with linear regression analysis. The goodness-of-fit for each calculated formula was evaluated by means of the coefficient of determination (r(2)). The agreement between Qs/Qt and F-shunt was analysed with the Bland-Altman test. All tested oxygen tension-based indices were weakly correlated (r(2) < 0.2) with the Qs/Qt, whereas F-shunt showed a stronger correlation (r(2) = 0.73). F-shunt also showed substantial agreement with Qs/Qt independent of the dobutamine infusion rate. F-shunt better correlated with Qs/Qt than other oxygen indices in isoflurane-anaesthetised horses under different infusion rates of dobutamine. PMID:25920771

  8. Vapor resistant arteries

    NASA Technical Reports Server (NTRS)

    Shaubach, Robert M. (Inventor); Dussinger, Peter M. (Inventor); Buchko, Matthew T. (Inventor)

    1989-01-01

    A vapor block resistant liquid artery structure for heat pipes. A solid tube artery with openings is encased in the sintered material of a heat pipe wick. The openings are limited to that side of the artery which is most remote from the heat source. The liquid in the artery can thus exit the artery through the openings and wet the sintered sheath, but vapor generated at the heat source is unlikely to move around the solid wall of the artery and reverse its direction in order to penetrate the artery through the openings. An alternate embodiment uses finer pore size wick material to resist vapor entry.

  9. Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

    PubMed

    Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

    2015-09-01

    Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease.

  10. Enhanced Extracorporeal CO2 Removal by Regional Blood Acidification: Effect of Infusion of Three Metabolizable Acids.

    PubMed

    Scaravilli, Vittorio; Kreyer, Stefan; Linden, Katharina; Belenkiy, Slava; Pesenti, Antonio; Zanella, Alberto; Cancio, Leopoldo C; Batchinsky, Andriy I

    2015-01-01

    Acidification of blood entering a membrane lung (ML) with lactic acid enhances CO2 removal (VCO2ML). We compared the effects of infusion of acetic, citric, and lactic acids on VCO2ML. Three sheep were connected to a custom-made circuit, consisting of a Hemolung device (Alung Technologies, Pittsburgh, PA), a hemofilter (NxStage, NxStage Medical, Lawrence, MA), and a peristaltic pump recirculating ultrafiltrate before the ML. Blood flow was set at 250 ml/min, gas flow (GF) at 10 L/min, and recirculating ultrafiltrate flow at 100 ml/min. Acetic (4.4 M), citric (0.4 M), or lactic (4.4 M) acids were infused in the ultrafiltrate at 1.5 mEq/min, for 2 hours each, in randomized fashion. VCO2ML was measured by the Hemolung built-in capnometer. Circuit and arterial blood gas samples were collected at baseline and during acid infusion. Hemodynamics and ventilation were monitored. Acetic, citric, or lactic acids similarly enhanced VCO2ML (+35%), from 37.4 ± 3.6 to 50.6 ± 7.4, 49.8 ± 5.6, and 52.0 ± 8.2 ml/min, respectively. Acids similarly decreased pH, increased pCO2, and reduced HCO3 of the post-acid extracorporeal blood sample. No significant effects on arterial gas values, ventilation, or hemodynamics were observed. In conclusion, it is possible to increase VCO2ML by more than one-third using any one of the three metabolizable acids.

  11. In vivo laser assisted end-to-end anastomosis with ICG-infused chitosan patches

    NASA Astrophysics Data System (ADS)

    Rossi, Francesca; Matteini, Paolo; Esposito, Giuseppe; Scerrati, Alba; Albanese, Alessio; Puca, Alfredo; Maira, Giulio; Rossi, Giacomo; Pini, Roberto

    2011-07-01

    Laser assisted vascular repair is a new optimized technique based on the use of ICG-infused chitosan patch to close a vessel wound, with or even without few supporting single stitches. We present an in vivo experimental study on an innovative end-to-end laser assisted vascular anastomotic (LAVA) technique, performed with the application of ICGinfused chitosan patches. The photostability and the mechanical properties of ICG-infused chitosan films were preliminary measured. The in vivo study was performed in 10 New Zealand rabbits. After anesthesia, a 3-cm segment of the right common carotid artery was exposed, thus clamped proximally and distally. The artery was then interrupted by means of a full thickness cut. Three single microsutures were used to approximate the two vessel edges. The ICG-infused chitosan patch was rolled all over the anastomotic site and welded by the use of a diode laser emitting at 810 nm and equipped with a 300 μm diameter optical fiber. Welding was obtained by delivering single laser spots to induce local patch/tissue adhesion. The result was an immediate closure of the anastomosis, with no bleeding at clamps release. Thus animals underwent different follow-up periods, in order to evaluate the welded vessels over time. At follow-up examinations, all the anastomoses were patent and no bleeding signs were documented. Samples of welded vessels underwent histological examinations. Results showed that this technique offer several advantages over conventional suturing methods: simplification of the surgical procedure, shortening of the operative time, better re-endothelization and optimal vascular healing process.

  12. [Postoperative analgesia with tramal in newborn children using the method of continuous intravenous infusion].

    PubMed

    Mikhel'son, V A; Zhirkova, Iu V; Beliaeva, I D; Stepanenko, S M; Manerova, A F; Butyleva, O Iu

    2003-01-01

    The purpose of the study was to evaluate the efficiency of postoperative analgesia with tramal in the newborns. Analgesia with tramal (5% solution for injections, "Gruonental GmbH", Germany) was administered postoperatively in 20 newborn children. Thirteen children were operated for congenital malformations in the gastrointestinal and urinary tracts, three children were operated for purulent-septic diseases and four children were operated for neoplasms. Hemodynamics indices, i.e. heart rate (HR) and arterial pressure, as well as SaO2, respiratory rate (RR), acid-base condition and behavioral reactions were assessed. Analgesia was implemented by the method of continuous intravenous infusion of tramal, 0.1-0.2 mg/kg.h combined with boluses, 1-2 mg/kg. The newborns were asleep for a major part of time during analgesia with tamal; the stable indices of hemodynamics, acid-base balance, glycemia and of the cortisol level were registered. Arterial hypertension, caused by several factors including the effect produced by tamal, was noted in 70% of children. Dose-dependent hypercapnia was registered in 80% of tests in children at unassisted respiration during the infusion of tamal, which is indicative of that tamal affects the respiratory center during the neonatal period and that it is necessary to monitor thoroughly the respiratory functions, i.e. RR, SatO2, pO2, pCO2, and to choose accurately a preparation dose. The continuous infusion of tamal ensures a sufficient analgesia after different operations and especially after medium-traumatic operations.

  13. Effect of peri-operative intravenous infusion of lignocaine on haemodynamic responses to intubation, extubation and post-operative analgesia

    PubMed Central

    Jain, Shruti; Khan, Rashid M

    2015-01-01

    Background and Aims: Lignocaine in intravenous (IV) bolus dose has been used for minimising haemodynamic changes associated with intubation and extubation. Furthermore, IV infusion has been used for post-operative analgesia. We investigated whether IV peri-operative lignocaine (bolus and infusion) would be able to produce both the effects simultaneously in elective laparoscopic cholecystectomies. Methods: In this randomised prospective study, 60 patients undergoing elective laparoscopic cholecystectomy were randomly divided into two groups of 30 each. In Group A, patients received 6 ml normal saline as bolus over 10 min followed by 6 ml/h infusion whereas in Group B, patients received preservative free 2% lignocaine 1.5 mg/kg IV bolus (made to a volume of 6 ml with normal saline) administered over a period of 10 min and thereafter an infusion at a rate of 1.5 mg/kg/h (pre-diluted in normal saline made to a volume of 6 ml/h. P < 0.05 was considered as significant. Results: The rise in pulse rate (PR) and mean arterial pressure (MAP) were less in Group B as compared to the Group A (P < 0.05) during intubation as well as during extubation. Furthermore, the Group B had significant longer mean pain-free post-operative period of 5½ h as compared to 54.43 min in the Group A (P < 0.05). Conclusion: Administration of lignocaine infusion attenuates the rise in PR as well as MAP during the peri-intubation and peri-extubation period. Furthermore, infusion of lignocaine significantly increases the mean pain-free period post-operatively. PMID:26195829

  14. Endothelial Cell Toxicity of Vancomycin Infusion Combined with Other Antibiotics

    PubMed Central

    Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

    2015-01-01

    French guidelines recommend central intravenous (i.v.) infusion for high concentrations of vancomycin, but peripheral intravenous (p.i.v.) infusion is often preferred in intensive care units. Vancomycin infusion has been implicated in cases of phlebitis, with endothelial toxicity depending on the drug concentration and the duration of the infusion. Vancomycin is frequently infused in combination with other i.v. antibiotics through the same administrative Y site, but the local toxicity of such combinations has been poorly evaluated. Such an assessment could improve vancomycin infusion procedures in hospitals. Human umbilical vein endothelial cells (HUVEC) were challenged with clinical doses of vancomycin over 24 h with or without other i.v. antibiotics. Cell death was measured with the alamarBlue test. We observed an excess cellular death rate without any synergistic effect but dependent on the numbers of combined infusions when vancomycin and erythromycin or gentamicin were infused through the same Y site. Incompatibility between vancomycin and piperacillin-tazobactam was not observed in our study, and rinsing the cells between the two antibiotic infusions did not reduce endothelial toxicity. No endothelial toxicity of imipenem-cilastatin was observed when combined with vancomycin. p.i.v. vancomycin infusion in combination with other medications requires new recommendations to prevent phlebitis, including limiting coinfusion on the same line, reducing the infusion rate, and choosing an intermittent infusion method. Further studies need to be carried out to explore other drug combinations in long-term vancomycin p.i.v. therapy so as to gain insight into the mechanisms of drug incompatibility under multidrug infusion conditions. PMID:26055373

  15. Effects of vascular infusion with a solution of saccharides, sodium chloride, and phosphates with or without vitamin C on carcass traits, Warner-Bratzler shear force, flavor-profile, and descriptive-attribute characteristics of steaks and ground beef from Charolais cattle.

    PubMed

    Yancey, E J; Dikeman, M E; Addis, P B; Katsanidis, E; Pullen, M

    2002-04-01

    Two groups of 18 grain-finished steers were utilized. Nine from one group were infused via the carotid artery immediately after jugular vein exsanguination with an aqueous solution containing saccharides, NaCl, and phosphates (MPSC; MPSC, Inc., Eden Prairie, MN, USA). Nine steers served as non-infused controls (CON). An additional 18 steers were infused with either MPSC (n=9) or MPSC plus 1000 ppm vitamin C (MPSC+C, n=9) solutions. Steers infused with MPSC had higher dressing percentages and organ weights than CON steers. Vascular infusion with MPSC had no effects on USDA yield or quality grade traits, descriptive-attribute sensory panel evaluations, or Warner-Bratzler shear force of longissimus lumborum and semitendinosus muscles. Vascular infusion with MPSC resulted in some significant, but inconsistent effects on flavor-profile characteristics of cooked beef. The addition of vitamin C to the MPSC solution did not provide any benefit. PMID:22063636

  16. Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. I. Theory.

    PubMed

    Hunter, M; Lee, J

    1992-11-01

    A dispersion and extraction model of the lung is developed to assess how the infusion of hypertonic saline into the pulmonary artery changes the gravimetric density of pulmonary venous blood. The dispersion analysis is built on the indicator dilution curve measured for the pulmonary circulation. The extraction model consists of microvascular and interstitial compartments separated by a permeable pulmonary endothelium. Because the density of fluid extracted by the hypertonic disturbance is lower than the blood density, the extraction leads to a decrease in blood density. Two cases of fluid extraction are analyzed, a hypertonic infusion to elevate the osmotic pressure in the pulmonary arterial blood in the form of a step function and an infusion performed over a period of 1 sec. Both cases show that the dispersion significantly attenuates the changes in osmotic pressure and density as they are transported by the blood along the pulmonary vasculature. Because the model has taken into account the effect of dispersion and pulmonary blood flow, the equations developed here provide the basis to calculate from the density change in pulmonary venous blood the characteristics of osmotic extraction intrinsic to the lung.

  17. Renal Artery Embolization Controls Intractable Pain in a Patient with Polycystic Kidney Disease

    SciTech Connect

    Hahn, Seong Tai; Park, Seog Hee; Lee, Jae Mun; Kim, Choon-Yul; Chang, Yoon Sik

    1999-09-15

    A 65-year-old man with adult polycystic kidney disease (APKD) and chronic renal failure suffered from intractable abdominal pain and distension for 2 weeks. Meperidine infusion did not alleviate his pain. However, pain and abdominal distension were successfully controlled by embolization of both renal arteries.

  18. [Abnormal popliteal arteries].

    PubMed

    Elbaz, C

    1975-01-01

    Arteriopathy restricted to the popliteal artery, except in cases of atheroma, must indicate three of four unusual diagnoses: the trapped popliteal artery and the dessicating haematoma are anatomo-clinical entities that have been identified only relatively recently. The popliteal artery may be trapped by the medial gastrocnomius muscle, round the tendon of which the artery passes (totally or partially). This results in compression of the artery and eventually in thrombosis. Clinically, intermittent claudication is seen that may deteriorate and lead to gangrene of the toes. Arteriography makes it possible to diagnose the condition as the condition as the artery is considerably displaced inwards. Surgical correction is simple: sectioning of the tendon and repositioning of the artery. Dessicating haematoma of the popliteal artery is due essentially to atheroma, associated with medianecrosis. A "egg-timer" stenosis is found by arteriography and this condition also progresses towards thrombosis. Arterial restoration is called for, usually by bridging. PMID:1230799

  19. MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

    PubMed

    Kim, Dong-Hyun; Chen, Jeane; Omary, Reed A; Larson, Andrew C

    2015-01-01

    Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies. A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion. This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes.

  20. [Neurological symptoms following infusion of infliximab].

    PubMed

    Bebe, Anna C K M; Harboe, Kirstine Moll; Nøjgaard, Camilla

    2012-10-01

    Infliximab is indicated for treatment of plaque psoriasis when traditional systemic therapy is inadequate or inappropriate. The treatment is efficient but also carries a risk of serious adverse drug events. We describe a case of neurological symptoms following the first infusion of infliximab in a patient treated for plaque psoriasis. The patient fully recovered after sensation of the therapy. We believe the symptoms could be related to infliximab and stress the importance of thorough information of patients treated with tumour necrosis factor-α-inhibitors, also about the risk of serious adverse events.

  1. Interactions between CO2 chemoreflexes and arterial baroreflexes

    NASA Technical Reports Server (NTRS)

    Henry, R. A.; Lu, I. L.; Beightol, L. A.; Eckberg, D. L.

    1998-01-01

    We studied interactions between CO2 chemoreflexes and arterial baroreflexes in 10 supine healthy young men and women. We measured vagal carotid baroreceptor-cardiac reflexes and steady-state fast Fourier transform R-R interval and photoplethysmographic arterial pressure power spectra at three arterial pressure levels (nitroprusside, saline, and phenylephrine infusions) and three end-tidal CO2 levels (3, 4, and 5%, fixed-frequency, large-tidal-volume breathing, CO2 plus O2). Our study supports three principal conclusions. First, although low levels of CO2 chemoreceptor stimulation reduce R-R intervals and R-R interval variability, statistical modeling suggests that this effect is indirect rather than direct and is mediated by reductions of arterial pressure. Second, reductions of R-R intervals during hypocapnia reflect simple shifting of vagally mediated carotid baroreflex responses on the R-R interval axis rather than changes of baroreflex gain, range, or operational point. Third, the influence of CO2 chemoreceptor stimulation on arterial pressure (and, derivatively, on R-R intervals and R-R interval variability) depends critically on baseline arterial pressure levels: chemoreceptor effects are smaller when pressure is low and larger when arterial pressure is high.

  2. Effect of central glucagon infusion on macronutrient selection in rats.

    PubMed

    Komenami, N; Su, F H; Thibault, L

    1996-02-01

    Compared were the light-dark pattern of absolute energy intake and macronutrient selection of male Wistar rats intracerebroventricularly infused with glucagon (5 ng/h) or saline for 7 days in a three-way selection of macronutrients. Glucagon infusion induced a decrease in 24 h and nocturnal energy intake, whereas no significant change in kcal intake accompanied vehicle infusion. The decrease in kcal intake was due to a suppression of nocturnal ingestion of carbohydrate. This parameter was left unaffected with central vehicle infusion. Glucagon-infused rats had a significantly lower body weight gain than those infused with vehicle. Our study supports the hypothesis of central glucagon's suppressive effect on food intake, but reveals that the latter reflects a lower disposition to eat carbohydrate during the dark phase. The present work emphasizes the role of glucagon in the circadian regulation of carbohydrate intake.

  3. Cooled artery extension

    NASA Technical Reports Server (NTRS)

    Gernert, Nelson J. (Inventor)

    1990-01-01

    An artery vapor trap. A heat pipe artery is constructed with an extension protruding from the evaporator end of the heat pipe beyond the active area of the evaporator. The vapor migrates into the artery extension because of gravity or liquid displacement, and cooling the extension condenses the vapor to liquid, thus preventing vapor lock in the working portion of the artery by removing vapor from within the active artery. The condensed liquid is then transported back to the evaporator by the capillary action of the artery extension itself or by wick located within the extension.

  4. Supercritical Fluid Infusion of Iron Additives in Polymeric Matrices

    NASA Technical Reports Server (NTRS)

    Nazem, Negin; Taylor, Larry T.

    1999-01-01

    The objective of this project was the experimentation to measure preparation of iron nanophases within polymeric matrices via supercritical fluid infusion of iron precursors followed by thermal reduction. Another objective was to determine if supercritical CO2 could infuse into the polymer. The experiment is described along with the materials, and the supercritical fluid infusion and cure procedures. X-ray photoelectron spectra and transmission electron micrographs were obtained. The results are summarized in charts, and tables.

  5. Theophylline: constant-rate infusion predictions.

    PubMed

    Mesquita, C A; Sahebjami, H; Imhoff, T; Thomas, J P; Myre, S A

    1984-01-01

    This study was undertaken to evaluate a method of prospectively estimating appropriate aminophylline infusion rates in acutely ill, hospitalized patients with bronchospasm. Steady-state serum theophylline concentrations (Css), clearances (Cl), and half-lives (t1/2) were estimated by the Chiou method using serum concetrantions obtained 1 and 6 h after the start of a constant-rate intravenous aminophylline infusion in 10 male patients averaging 57 years of age. Using an enzyme-multiplied immunoassay (EMIT) system for theophylline analysis, pharmacokinetic estimations were excellent for Css (r = 0.9103, p less than 0.01) and Cl (r = 0.9750, p less than 0.01). The mean estimation errors were 9.4% (range 0.8-21.5) for Css and 12.3% (range 1.3-28.0) for Cl. There was no correlation between patient age and Cl. This method is useful for rapidly individualizing aminophylline therapy in patients with acute bronchospasm. PMID:6740734

  6. Implantable Micropump Technologies for Murine Intracochlear Infusions

    PubMed Central

    Johnson, D. G.; Waldron, M. J.; Frisina, R. D.; Borkholder, D. A.

    2011-01-01

    Due to the very small size of the mouse inner ear, 600 nL volume, developing effective, controlled infusion systems is quite challenging. Key technologies have been created to minimize both size and power for an implantable pump for murine intracochlear infusions. A method for coupling fine capillary tubing to microfluidic channels is presented which provides low volume, biocompatible interconnects withstanding pressures as high as 827 kPa (120 psi) and consuming less than 20 nL of volume exiting in-plane with the pump. Surface micromachined resistive bridges integrated into the flow channel for anemometry based flow rate measurement have been optimized for low power operation in the ultra-low flow rate regime. A process for creation of deformable diaphragms over pump chambers with simultaneous coating of the microfluidic channels has been developed allowing integration of a biocompatible fluid flow path. These advances represent enabling capabilities for a drug delivery system suitable for space constrained applications such as subcutaneous implantation in mice. PMID:21096713

  7. [Intracranial pressure and hypotonic infusion solutions].

    PubMed

    Zander, R

    2009-04-01

    The physiological osmolality of plasma is 288+/-5 mosmol/kgH2O when measured by freezing-point depression. The theoretical osmolarity (290 mosmol/l) calculated from composition, osmotic coefficient (0.93) and water content (0.94) is practically identical. Saline (0.9% NaCl) has an osmolarity of 308 mosmol/l and an osmolality of 286 mosmol/kgH2O (water content ca. 1.0). The osmolality in vivo is more important than that measured in vitro. A 5% dextrose solution in water (D5W) is isotonic in vitro, but the in vivo effect is that of pure water because the glucose is rapidly metabolized. Every infusion fluid should be isotonic (290+/-10 mosmol/kgH2O). Hypotonic solutions must move water from the extracellular space to the intracellular space. Typical examples are Ringer's lactate and acetate solutions (256 instead of 290 mosmol/kgH2O). The brain (central nervous system, CNS) is the critical organ: The rigidly shaped skull contains three incompressible compartments, only blood and cerebrospinal fluid (CSF) can be partially, but limitedly shifted outside the skull. The consequence of a volume load is an increasing intracranial pressure (ICP). A decrease in plasma osmolality by only 3% produces an increase in ICP of about 15 mmHg. Therefore, infusion of larger volumes of hypotonic solutions should be avoided at all costs.

  8. Controlled release infusion kinetics of tobramycin.

    PubMed

    Lane, J R; Murray, W E; Willenborg, N L; Wilcox, C L; Connor, J D; Adler, D S

    1989-01-01

    Ten healthy male volunteers received two doses of tobramycin (2 mg/kg) in a crossover fashion, first by intravenous piggyback (IVPB), then by the CRIS infusion system after a washout period. Serum samples were drawn both during and after the infusions. Twenty-four-hour urine collections were assayed for tobramycin. Residual fluid from the lines of both delivery systems was measured and assayed for tobramycin concentration. All samples were run in duplicate, using an enzyme-multiplied immunoassay technique assay. The results indicate that there was a statistically higher amount of drug delivered via the CRIS system (98.3 +/- 0.3% versus 90.4 +/- 2.3%). No significant difference was found in urinary recovery between the two groups. Peak serum levels were significantly higher with the CRIS system, with 8/10 subjects having at least one serum level greater than 10 micrograms/ml, as compared to 0/10 when given by IVPB. Peak serum levels occurred at 30 min in all subjects given tobramycin through the CRIS system, compared to 50-60 min when delivered by IVPB. This difference in peak serum levels is primarily related to the rate of drug delivery and to the difference in the dose delivered to each subject. The significance of the serum concentration profiles is discussed.

  9. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

    Giers, Günther; Wenzel, Folker; Stockschläder, Markus; Riethmacher, Regina; Lorenz, Horst; Tutschek, Boris

    2010-01-01

    Background Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and Methods We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. Results There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×109/L and 130×109/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. Conclusions In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions. PMID:20534698

  10. Infusion pump inspection frequencies. How often is inspection really needed?

    PubMed

    1998-01-01

    As noted in this issue's Evaluation of infusion pump analyzers, the frequency at which a facility inspects its infusion pumps can help determine its need for one or more analyzers. It can also have a financial impact on the clinical engineering department. In this article, we discuss inspection issues affecting infusion pumps, including our recommendations and how facilities can set intervals for their equipment. (For ECRI's procedure for inspecting infusion devices, refer to Procedure/Checklist 416-0595 in the Health Devices Inspection and Preventive Maintenance [IPM] System; contact ECRI's Communications Department at [610] 825-6000, ext. 888, for more information about this publication.) PMID:9595314

  11. Broadening infusion specialization as an adjunct to organizational sustainability.

    PubMed

    Meyer, Britt M

    2014-01-01

    As changes in reimbursement structures create a stringent focus on the prevention of infection and other infusion-related complications that predispose to infection, it becomes important to examine the impact of vascular access and infusion specialty practices and procedures on overall organization sustainability and to implement strategies for disseminating infusion expertise to a broader contingent of nurses. This article discusses infusion nursing practice as it impacts the organization as a whole and details a performance improvement initiative for implementing a novel peripherally inserted central catheter tip determination technology that encompasses many of the goals of the industry standards. PMID:24384884

  12. Endothelin Receptor Subtype Distribution Predisposes Coronary Arteries to Damage

    PubMed Central

    Louden, Calvert S.; Nambi, Ponnal; Pullen, Mark A.; Thomas, Roberta A.; Tierney, Lauren A.; Solleveld, Henk A.; Schwartz, Lester W.

    2000-01-01

    Several vasoactive drugs that lower blood pressure and increase heart rate induce regional cardiotoxicity in the dog, most frequently of right coronary arteries and right atrium. The basis for this selective damage is thought to result from local changes in vascular tone and blood flow. Administration of an endothelin receptor antagonist (ETRA, SB 209670) to dogs induced damage most frequent and severe in the right coronary artery and right atrium. Because site predisposition may correlate with distribution of vasoactive receptors, the objectives of this study were to map endothelin (ET) receptor distribution and density within regions of dog heart using both gene (mRNA) and protein expression endpoints for dog ETA and ETB receptors, and, additionally, correlate ET receptor subtype density with regional cardiac blood flow. A 10- to 15-mmHg reduction in mean arterial pressure with a concomitant increase in heart rate (10–20%), a six- and twofold increase in regional blood flow to the right and left atrium, respectively, and acute hemorrhage, medial necrosis, and inflammation were observed in the right coronary arteries and arteries of the right atrium after ETRA infusion for 5 days. Radioligand protein binding to quantify both ET receptors in normal dog heart indicated a twofold greater density of ET receptors in atrial regions versus ventricular regions. Importantly, ET receptor density in coronary arteries was markedly (about five- to sixfold) increased above that in atrial or ventricular tissues. ET receptor subtype characterization indicated ETB receptors were three times more prevalent in right coronary arteries compared to left coronary arteries and in situ hybridization confirmed localization of ETB in vascular smooth muscle. ETA receptor density was comparable in right and left coronary arteries. Quantitative real-time polymerase chain reaction for ETA and ETB receptor mRNA transcripts supported the site prevalence for message distribution. Consequently

  13. Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report

    PubMed Central

    2010-01-01

    Introduction Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. Case presentation We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. Conclusions This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation. PMID:20525186

  14. O-(beta-hydroxyethyl)-rutoside (Venoruton) fails to block histamine or bradykinin-induced edema formation in the canine forelimb perfused at constant arterial inflow.

    PubMed

    Dobbins, D E; Soika, C Y; Dabney, J M

    1984-10-01

    O-(beta-hydroxyethyl)-rutoside (Venoruton) has been reported to alleviate edema formation in chronic venous insufficiency. In an attempt to elucidate Venoruton's potential as an antiinflammatory agent, we infused Venoruton (20 mg/minute) intraarterially into the canine forelimb perfused at constant flow during the simultaneous intraarterial infusion of histamine (4 micrograms base/minute) or bradykinin (2 micrograms/minute). The infusion of Venoruton alone for forty minutes resulted in a small but significant increase in forelimb arterial pressures but no change in systemic pressure or forelimb skin lymph flow, protein concentration or protein transport. Subsequent infusion of either histamine or bradykinin resulted in a significant decrease in forelimb arterial pressures and a marked increase in skin lymph flow, lymph total protein concentration and lymph total protein transport. The changes in forelimb vascular pressures and skin lymph parameters were similar to those seen during the infusion of either histamine or bradykinin alone. These data indicate that the intraarterial infusion of Venoruton at this dosage does not inhibit the ability of simultaneously infused histamine or bradykinin to increase transvascular fluid and macromolecular efflux in the canine forelimb perfused at constant arterial inflow.

  15. Coronary Artery Disease

    MedlinePlus

    Coronary artery disease (CAD) is the most common type of heart disease. It is the leading cause of death ... both men and women. CAD happens when the arteries that supply blood to heart muscle become hardened ...

  16. Peripheral Artery Disease (PAD)

    MedlinePlus

    ... changes and medication . View an animation of atherosclerosis Atherosclerosis and PAD Atherosclerosis is a disease in which plaque builds up ... of an artery. PAD is usually caused by atherosclerosis in the peripheral arteries (or outer regions away ...

  17. Coronary artery fistula

    MedlinePlus

    Congenital heart defect - coronary artery fistula; Birth defect heart - coronary artery fistula ... attaches to one of the chambers of the heart (the atrium or ventricle) or another blood vessel ( ...

  18. Occlusive Peripheral Arterial Disease

    MedlinePlus

    ... artery. Such people should seek medical care immediately. Did You Know... When people suddenly develop a painful, ... In This Article Animation 1 Peripheral Arterial Disease Did You Know 1 Did You Know... Figure 1 ...

  19. Carotid Artery Disease

    MedlinePlus

    ... and efficacy continues to be studied in several medical centers. This procedure involves the placement of a small flexible tube (catheter) into an artery from the groin. The catheter is then directed to the neck to reach the carotid artery blockage. A balloon pushes open the artery wall and a stent ( ...

  20. Mutation of the protein-O-mannosyltransferase enhances secretion of the human urokinase-type plasminogen activator in Hansenula polymorpha.

    PubMed

    Agaphonov, Michael O; Sokolov, Sviatoslav S; Romanova, Nina V; Sohn, Jung-Hoon; Kim, So-Young; Kalebina, Tatyana S; Choi, Eui-Sung; Ter-Avanesyan, Michael D

    2005-10-15

    Human urokinase-type plasminogen activator (uPA) is poorly secreted and aggregates in the endoplasmic reticulum of yeast cells due to inefficient folding. A screen for Hansenula polymorpha mutants with improved uPA secretion revealed a gene encoding a homologue of the Saccharomyces cerevisiae protein-O-mannosyltransferase Pmt1p. Expression of the H. polymorpha PMT1 gene (HpPMT1) abolished temperature sensitivity of the S. cerevisiae pmt1 pmt2 double mutant. As in S. cerevisiae, inactivation of the HpPMT1 gene affected electrophoretic mobility of the O-glycosylated protein, extracellular chitinase. In contrast to S. cerevisiae, disruption of HpPMT1 alone caused temperature sensitivity. Inactivation of the HpPMT1 gene decreased intracellular aggregation of uPA, suggesting that enhanced secretion of uPA was due to improvement of its folding in the endoplasmic reticulum. Unlike most of the endoplasmic reticulum membrane proteins, HpPmt1p possesses the C-terminal KDEL retention signal. PMID:16200504

  1. Risk factors associated with serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor in a general population.

    PubMed

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line Jh; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  2. CHK1 and RAD51 activation after DNA damage is regulated via urokinase receptor/TLR4 signaling

    PubMed Central

    Narayanaswamy, Pavan B; Tkachuk, Sergey; Haller, Hermann; Dumler, Inna; Kiyan, Yulia

    2016-01-01

    Mechanisms of DNA damage and repair signaling are not completely understood that hinder the efficiency of cancer therapy. Urokinase-type plasminogen activator receptor (PLAUR) is highly expressed in most solid cancers and serves as a marker of poor prognosis. We show that PLAUR actively promotes DNA repair in cancer cells. On the contrary, downregulation of PLAUR expression results in delayed DNA repair. We found PLAUR to be essential for activation of Checkpoint kinase 1 (CHK1); maintenance of cell cycle arrest after DNA damage in a TP53-dependent manner; expression, nuclear import and recruitment to DNA-damage foci of RAD51 recombinase, the principal protein involved in the homologous recombination repair pathway. Underlying mechanism implies auto-/paracrine signaling of PLAUR/TLR4 receptor complex leading to activation of CHK1 and DNA repair. The signaling is induced by a danger molecule released by DNA-damaged cells and mediates, at least partially, activation of DNA-damage response. This study describes a new mechanism of DNA repair activation initiated by auto-/paracrine signaling of membrane receptors PLAUR/TLR4. It adds to the understanding of role of PLAUR in cancer and provides a rationale for therapeutic targeting of PLAUR/TLR4 interaction in TP53-positive cancers. PMID:27685627

  3. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders

    PubMed Central

    Toldi, Gergely; Balog, Attila

    2016-01-01

    The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges. PMID:27683525

  4. Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

    PubMed Central

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line JH; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  5. A high-affinity receptor for urokinase plasminogen activator on human keratinocytes: characterization and potential modulation during migration.

    PubMed Central

    McNeill, H; Jensen, P J

    1990-01-01

    Low passage cultures of normal human keratinocytes produce several components of the plasminogen activator/plasmin proteolytic cascade, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and two specific inhibitors. Studies here presented demonstrate that these cells also contain a high-affinity (Kd = 3 x 10(-10) M) plasma membrane-binding site for uPA. High molecular weight uPA, either as the single-chain precursor or two-chain activated form, bound to the receptor; however, low molecular weight (33 kD) uPA, tPA, or epidermal growth factor did not compete for binding, demonstrating specificity. Acid treatment, which removed endogenous uPA from the receptor, was required to detect maximal binding (45,000 sites per cell). To investigate the possibility that the uPA receptor on keratinocytes may be involved in epithelial migration during wound repair, cultures were wounded and allowed to migrate into the wounded site. Binding sites for uPA were localized by autoradiographic analysis of 125I-uPA binding as well as by immunocytochemical studies using anti-uPA IgG. With both techniques uPA binding sites were detected selectively on the plasma membrane of cells at the leading edge of the migrating epithelial sheet. This localization pattern suggests that uPA receptor expression on keratinocytes may be coupled to cell migration during cutaneous wounding. Images PMID:1965151

  6. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders.

    PubMed

    Vasarhelyi, Barna; Toldi, Gergely; Balog, Attila

    2016-04-01

    The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges. PMID:27683525

  7. Administration of Recombinant Soluble Urokinase Receptor Per Se Is Not Sufficient to Induce Podocyte Alterations and Proteinuria in Mice

    PubMed Central

    Cathelin, Dominique; Placier, Sandrine; Ploug, Michael; Verpont, Marie-Christine; Vandermeersch, Sophie; Luque, Yosu; Hertig, Alexandre; Rondeau, Eric

    2014-01-01

    Circulating levels of soluble forms of urokinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and adults with FSGS compared with levels in healthy persons or those with other types of kidney disease. In mice lacking the gene encoding uPAR, forced increases in suPAR concentration result in FSGS-like glomerular lesions and proteinuria. However, whether overexpression of suPAR, per se, contributes to the pathogenesis of FSGS in humans remains controversial. We conducted an independent set of animal experiments in which two different and well characterized forms of recombinant suPAR produced by eukaryotic cells were administered over the short or long term to wild-type (WT) mice. In accordance with the previous study, the delivered suPARs are deposited in the glomeruli. However, such deposition of either form of suPAR in the kidney did not result in increased glomerular proteinuria or altered podocyte architecture. Our findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficient to engender albuminuria. PMID:24790179

  8. Structure-based Engineering of Species Selectivity in the Interaction Between Urokinase and its Receptor: Implication for Preclinical Cancer Therapy

    SciTech Connect

    Lin, L.; Gardsvoll, H; Huai, Q; Huang, M; Ploug, M

    2010-01-01

    The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) is decisive for cell surface-associated plasminogen activation. Because plasmin activity controls fibrinolysis in a variety of pathological conditions, including cancer and wound healing, several intervention studies have focused on targeting the uPA {center_dot} uPAR interaction in vivo. Evaluations of such studies in xenotransplanted tumor models are, however, complicated by the pronounced species selectivity in this interaction. We now report the molecular basis underlying this difference by solving the crystal structure for the murine uPA {center_dot} uPAR complex and demonstrate by extensive surface plasmon resonance studies that the kinetic rate constants for this interaction can be swapped completely between these orthologs by exchanging only two residues. This study not only discloses the structural basis required for a successful rational design of the species selectivity in the uPA {center_dot} uPAR interaction, which is highly relevant for functional studies in mouse models, but it also suggests the possible development of general inhibitors that will target the uPA {center_dot} uPAR interaction across species barriers.

  9. Pharmacokinetics of continuous-infusion meropenem in a pediatric patient receiving extracorporeal life support.

    PubMed

    Cies, Jeffrey J; Moore, Wayne S; Dickerman, Mindy J; Small, Christine; Carella, Dominick; Chopra, Arun; Parker, Jason

    2014-10-01

    Meropenem, a broad-spectrum carbapenem, is commonly used for empirical and definitive therapy in the pediatric intensive care unit (ICU). Pharmacokinetic data to guide dosing in children, however, are limited to healthy volunteers or patients who are not in the ICU. Adult data demonstrate that pharmacokinetic parameters such as the volume of distribution and clearance can be significantly altered in individuals receiving extracorporeal membrane oxygenation (ECMO). Alterations in the volume of distribution and clearance of antimicrobials in patients with sepsis and septic shock have also been documented, and these patients have demonstrated lower than expected antimicrobial serum concentrations based on standard dosing regimens. Therefore, an understanding of the pharmacokinetic changes in critically ill children receiving ECMO is crucial to determining the most appropriate dose and dosing interval selection for any antimicrobial therapy. In this case report, we describe the pharmacokinetics of a continuous infusion of meropenem in a pediatric cardiac ICU patient who was receiving concurrent extracorporeal life support. The patient was an 8-month-old male infant who underwent a Glenn procedure and pulmonary artery reconstruction. Postoperatively, he required ECMO with a total run of 21 days. On day 11 of ECMO, a bronchoalveolar lavage was performed, and blood cultures from days 11 and 12 of ECMO grew Pseudomonas aeruginosa, with a meropenem minimum inhibitory concentration (MIC) of 0.5 μg/ml. On ECMO day 13, meropenem was initiated with a loading dose of 40 mg/kg and infused over 30 minutes, followed by a continuous infusion of 200 mg/kg/day. A meropenem serum concentration measured 8 hours after the start of the infusion was 46 μg/ml. Repeat levels were measured on days 3 and 9 of meropenem therapy and were 39 and 42 μg/ml, respectively. Repeat blood and respiratory cultures remained negative. This meropenem regimen (40-mg/kg bolus followed by a

  10. Infused polymers for cell sheet release

    NASA Astrophysics Data System (ADS)

    Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

    2016-05-01

    Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering.

  11. Infused polymers for cell sheet release

    PubMed Central

    Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

    2016-01-01

    Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering. PMID:27189419

  12. Haemodynamic responses to exercise, ATP infusion and thigh compression in humans: insight into the role of muscle mechanisms on cardiovascular function

    PubMed Central

    González-Alonso, José; Mortensen, Stefan P; Jeppesen, Tina D; Ali, Leena; Barker, Horace; Damsgaard, Rasmus; Secher, Niels H; Dawson, Ellen A; Dufour, Stéphane P

    2008-01-01

    The muscle pump and muscle vasodilatory mechanims are thought to play important roles in increasing and maintaining muscle perfusion and cardiac output during exercise, but their actual contributions remain uncertain. To evaluate the role of the skeletal muscle pump and vasodilatation on cardiovascular function during exercise, we determined leg and systemic haemodynamic responses in healthy men during (1) incremental one-legged knee-extensor exercise, (2) step-wise femoral artery ATP infusion at rest, (3) passive exercise (n = 10), (4) femoral vein or artery ATP infusion (n = 6), and (5) cyclic thigh compressions at rest and during passive and voluntary exercise (n = 7). Incremental exercise resulted in progressive increases in leg blood flow (ΔLBF 7.4 ± 0.7 l min−1), cardiac output ( 8.7 ± 0.7 l min−1), mean arterial pressure (ΔMAP 51 ± 5 mmHg), and leg and systemic oxygen delivery and . Arterial ATP infusion resulted in similar increases in , LBF, and systemic and leg oxygen delivery, but central venous pressure and muscle metabolism remained unchanged and MAP was reduced. In contrast, femoral vein ATP infusion did not alter LBF, or MAP. Passive exercise also increased blood flow (ΔLBF 0.7 ± 0.1 l min−1), yet the increase in muscle and systemic perfusion, unrelated to elevations in aerobic metabolism, accounted only for ∼5% of peak exercise hyperaemia. Likewise, thigh compressions alone or in combination with passive exercise increased blood flow (ΔLBF 0.5–0.7 l min−1) without altering , MAP or . These findings suggest that the skeletal muscle pump is not obligatory for sustaining venous return, central venous pressure, stroke volume and or maintaining muscle blood flow during one-legged exercise in humans. Further, its contribution to muscle and systemic peak exercise hyperaemia appears to be minimal in comparison to the effects of muscle vasodilatation. PMID:18339690

  13. The contribution of the arterial chemoreceptors to the stimulation of respiration by adrenaline and noradrenaline in the cat

    PubMed Central

    Joels, N.; White, H.

    1968-01-01

    1. Intravenous infusions of adrenaline and noradrenaline in doses averaging 0·8 μg/kg.min increased the respiratory minute volume of anaesthetized cats breathing room air. The mean increase in respiratory minute volume was 14% during adrenaline infusion and 8% during noradrenaline infusion. 2. In a small group of decerebrate cats infusions of adrenaline and noradrenaline increased ventilation by 19 and 27% respectively. 3. Intravenous catecholamine infusions also increased the respiratory responses of anaesthetized animals to the inhalation of 5% or 10% O2 in N2 and to the inhalation of 5% CO2 in air. 4. Adrenaline and noradrenaline infusions had no significant effect on the ventilation of animals breathing 100% O2, nor did they significantly alter the respiratory response to the inhalation of 5% CO2 in O2. 5. After section of the carotid sinus and aortic nerves, a blood-pressure compensator being used to minimize changes in arterial pressure, catecholamines had no effect on the respiration of cats breathing air. 6. An increase in carotid body chemoreceptor discharge accompanied the increase in ventilation during catecholamine infusion. 7. Intravenous catecholamine infusions still produced an increase in ventilation and carotid body chemoreceptor discharge after both aortic nerves and both cervical sympathetic nerves had been cut. 8. Intra-arterial infusions into one carotid artery of 0·2 μg/kg.min of adrenaline or 0·1 μg/kg.min of noradrenaline led to mean increases in respiratory minute volume of 9·9 and 11·5% respectively. No increase occurred after section of the corresponding carotid sinus nerve. Such infusions also evoked an increase in carotid body chemoreceptor discharge. 9. It is concluded that the hyperpnoea produced by adrenaline and noradrenaline infusions in the cat is predominantly reflex in origin and is mediated by the arterial chemoreceptors. 10. The increase in ventilation produced by adrenaline appears to have a component additional to

  14. Aortic Input Impedance during Nitroprusside Infusion

    PubMed Central

    Pepine, Carl J.; Nichols, W. W.; Curry, R. C.; Conti, C. Richard

    1979-01-01

    Beneficial effects of nitroprusside infusion in heart failure are purportedly a result of decreased afterload through “impedance” reduction. To study the effect of nitroprusside on vascular factors that determine the total load opposing left ventricular ejection, the total aortic input impedance spectrum was examined in 12 patients with heart failure (cardiac index <2.0 liters/min per m2 and left ventricular end diastolic pressure >20 mm Hg). This input impedance spectrum expresses both mean flow (resistance) and pulsatile flow (compliance and wave reflections) components of vascular load. Aortic root blood flow velocity and pressure were recorded continuously with a catheter-tip electromagnetic velocity probe in addition to left ventricular pressure. Small doses of nitroprusside (9-19 μg/min) altered the total aortic input impedance spectrum as significant (P < 0.05) reductions in both mean and pulsatile components were observed within 60-90 s. With these acute changes in vascular load, left ventricular end diastolic pressure declined (44%) and stroke volume increased (20%, both P < 0.05). Larger nitroprusside doses (20-38 μg/min) caused additional alteration in the aortic input impedance spectrum with further reduction in left ventricular end diastolic pressure and increase in stroke volume but no additional changes in the impedance spectrum or stroke volume occurred with 39-77 μg/min. Improved ventricular function persisted when aortic pressure was restored to control values with simultaneous phenylephrine infusion in three patients. These data indicate that nitroprusside acutely alters both the mean and pulsatile components of vascular load to effect improvement in ventricular function in patients with heart failure. The evidence presented suggests that it may be possible to reduce vascular load and improve ventricular function independent of aortic pressure reduction. PMID:457874

  15. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hetacillin potassium for intramammary infusion... § 526.1130 Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See...

  16. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hetacillin potassium for intramammary infusion... § 526.1130 Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See...

  17. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Hetacillin potassium for intramammary infusion... § 526.1130 Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See...

  18. Silos to Symphonies? Hopes and Challenges Implementing Multicultural Programme Infusion

    ERIC Educational Resources Information Center

    Liu, Laura B.; Milman, Natalie B.

    2013-01-01

    The need to infuse multicultural education (ME) across teacher preparation programmes is well documented by research, yet institutions are at very different stages in this endeavour. While most programmes demonstrate a segregated approach to ME, confining diversity to specialty courses, ME programme infusion places diversity, equity and social…

  19. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  20. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Hetacillin potassium for intramammary infusion... Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See No. 000010 in §...

  1. ArtsIN: Arts Integration and Infusion Framework

    ERIC Educational Resources Information Center

    Hartle, Lynn C.; Pinciotti, Patricia; Gorton, Rebecca L.

    2015-01-01

    Teaching to meet the diverse learning needs of twenty-first century, global learners can be challenging, yet a growing body of research points to the proved successes of arts-infused and integrated curricula, especially for building capacity for learning and motivation. This article presents the ArtsIN: Arts Integration and Infusion framework, a…

  2. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  3. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  4. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  5. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  6. Inhibition of endogenous lactate turnover with lactate infusion in humans

    SciTech Connect

    Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C. )

    1989-11-01

    The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U-{sup 14}C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production.

  7. Infusing Educational Technology in Teaching Methods Courses: Successes and Dilemmas

    ERIC Educational Resources Information Center

    Wetzel, Keith; Buss, Ray; Foulger, Teresa S.; Lindsey, LeeAnn

    2014-01-01

    In this action research study, we describe the implementation of a program to infuse technology in general methods courses as a requirement of a teacher preparation program. Results from teacher candidate focus groups revealed successes and dilemmas of infusing technology into the courses. Candidates ably described prospective use of elements of…

  8. Glucose supplementation stimulates peripheral branched-chain amino acid catabolism in lactating dairy cows during essential amino acid infusions.

    PubMed

    Nichols, K; Kim, J J M; Carson, M; Metcalf, J A; Cant, J P; Doelman, J

    2016-02-01

    To determine how glucose modulates protein synthesis when essential AA are in abundant supply, 5 early-lactation, rumen-fistulated Holstein dairy cows were fed a diet containing 6.95 MJ/kg of net energy for lactation and 12.4% crude protein and abomasally infused for 5 d with saline, 844 or 1,126 g/d of a complete essential AA mix, with and without the inclusion of 1,000 g/d of glucose, in a 5×5 Latin square design. Infusion of essential AA increased milk yield by 4.1 kg/d, milk protein by 256 g/d, milk fat by 95 g/d, and milk urea nitrogen by 70% compared with saline, with no differences between the level of essential AA infusion. The addition of glucose to essential AA infusate did not stimulate milk protein yield or concentration, but reduced milk urea nitrogen by 17% and decreased milk fat yield. Arterial concentrations of total essential AA increased 3- to 4-fold, mammary clearance decreased 61%, and mammary uptake of essential AA increased 65% in response to essential AA infusion. Arterial branched-chain AA concentrations declined 29% in response to glucose and mammary clearance increased 48%, but mammary AA uptake was unchanged. Essential AA infusion increased plasma 3-methylhistidine by 50% and reduced muscle branched-chain α-keto acid dehydrogenase kinase abundance by 14%, indicating stimulation of muscle protein turnover and branched-chain AA catabolism, respectively. Glucose had no further effect on muscle branched-chain α-keto acid dehydrogenase kinase abundance but decreased mRNA expression of branched chain aminotransferase 1. Lack of further increases in plasma 3-methylhistidine or greater stimulation of muscle branched-chain AA catabolism indicates that muscle protein degradation was unchanged with glucose but that accretion may have been stimulated. The decrease in circulating branched-chain AA concentrations and nitrogen excretion in response to glucose suggests that surplus essential AA were redirected to peripheral, extra-mammary tissues.

  9. [Upper extremity arterial diseases].

    PubMed

    Becker, F

    2007-02-01

    Compared to lower limb arterial diseases, upper limb arterial diseases look rare, heterogeneous with various etiologies and a rather vague clinical picture, but with a negligible risk of amputation. Almost all types of arterial diseases can be present in the upper limb, but the anatomical and hemodynamic conditions particular to the upper limb often confuse the issue. Thus, atherosclerosis affects mainly the subclavian artery in its proximal segment where the potential of collateral pathway is high making the symptomatic forms not very frequent whereas the prevalence of subclavian artery stenosis or occlusion is relatively high. The clinical examination and the etiologies are discussed according to the clinical, anatomical and hemodynamic context.

  10. Jet pump assisted artery

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A procedure for priming an arterial heat pump is reported; the procedure also has a means for maintaining the pump in a primed state. This concept utilizes a capillary driven jet pump to create the necessary suction to fill the artery. Basically, the jet pump consists of a venturi or nozzle-diffuser type constriction in the vapor passage. The throat of this venturi is connected to the artery. Thus vapor, gas, liquid, or a combination of the above is pumped continuously out of the artery. As a result, the artery is always filled with liquid and an adequate supply of working fluid is provided to the evaporator of the heat pipe.

  11. External artery heat pipe

    NASA Technical Reports Server (NTRS)

    Gernert, Nelson J. (Inventor); Ernst, Donald M. (Inventor); Shaubach, Robert M. (Inventor)

    1989-01-01

    An improved heat pipe with an external artery. The longitudinal slot in the heat pipe wall which interconnects the heat pipe vapor space with the external artery is completely filled with sintered wick material and the wall of the external artery is also covered with sintered wick material. This added wick structure assures that the external artery will continue to feed liquid to the heat pipe evaporator even if a vapor bubble forms within and would otherwise block the liquid transport function of the external artery.

  12. Combined hormonal infusion simulates the metabolic response to injury.

    PubMed Central

    Bessey, P Q; Watters, J M; Aoki, T T; Wilmore, D W

    1984-01-01

    To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses. PMID:6431917

  13. Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion

    PubMed Central

    Heinemann, Lutz; Krinelke, Lars

    2012-01-01

    Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient. PMID:22920824

  14. Multiple Intravenous Infusions Phase 2a: Ontario Survey

    PubMed Central

    Fan, Mark; Koczmara, Christine; Masino, Caterina; Cassano-Piché, Andrea; Trbovich, Patricia; Easty, Anthony

    2014-01-01

    Background Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. Objective To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. Data Sources and Review Methods Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). Results Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions administration of secondary infusions with/as high-alert continuous IV medications potential confusion about how IV tubing should be labelled to reflect replacement date and time interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units coadministration of continuous or intermittent infusions on central venous pressure monitoring ports variability in respondents’ awareness of the infusion pump's bolus capabilities Limitations Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. Conclusions The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID

  15. Multiple Intravenous Infusions Phase 2b: Laboratory Study

    PubMed Central

    Pinkney, Sonia; Fan, Mark; Chan, Katherine; Koczmara, Christine; Colvin, Christopher; Sasangohar, Farzan; Masino, Caterina; Easty, Anthony; Trbovich, Patricia

    2014-01-01

    Background Administering multiple intravenous (IV) infusions to a single patient via infusion pump occurs routinely in health care, but there has been little empirical research examining the risks associated with this practice or ways to mitigate those risks. Objectives To identify the risks associated with multiple IV infusions and assess the impact of interventions on nurses’ ability to safely administer them. Data Sources and Review Methods Forty nurses completed infusion-related tasks in a simulated adult intensive care unit, with and without interventions (i.e., repeated-measures design). Results Errors were observed in completing common tasks associated with the administration of multiple IV infusions, including the following (all values from baseline, which was current practice): setting up and programming multiple primary continuous IV infusions (e.g., 11.7% programming errors) identifying IV infusions (e.g., 7.7% line-tracing errors) managing dead volume (e.g., 96.0% flush rate errors following IV syringe dose administration) setting up a secondary intermittent IV infusion (e.g., 11.3% secondary clamp errors) administering an IV pump bolus (e.g., 11.5% programming errors) Of 10 interventions tested, 6 (1 practice, 3 technology, and 2 educational) significantly decreased or even eliminated errors compared to baseline. Limitations The simulation of an adult intensive care unit at 1 hospital limited the ability to generalize results. The study results were representative of nurses who received training in the interventions but had little experience using them. The longitudinal effects of the interventions were not studied. Conclusions Administering and managing multiple IV infusions is a complex and risk-prone activity. However, when a patient requires multiple IV infusions, targeted interventions can reduce identified risks. A combination of standardized practice, technology improvements, and targeted education is required. PMID:26316919

  16. Avoiding Infusion Confusion 7th through 9th Grades. A Practical Handbook for Infusing Environmental Activities into Your Classroom.

    ERIC Educational Resources Information Center

    Hayden, Harvey; And Others

    To some educators, infusing environmental education into different subject areas at different levels may seem like an insurmountable task. This handbook was developed to take the guesswork out of this process and alleviate the fear and confusion that may result. It was designed to assist with infusing knowledge, skill and attitude activities into…

  17. Effects of fluid preload (crystalloid or colloid) compared with crystalloid co-load plus ephedrine infusion on hypotension and neonatal outcome during spinal anaesthesia for caesarean delivery.

    PubMed

    Gunusen, I; Karaman, S; Ertugrul, V; Firat, V

    2010-07-01

    Preload with crystalloid or colloid solution is widely recommended for the prevention of maternal hypotension during spinal anaesthesia. A combination of simultaneous rapid crystalloid infusion with vasopressor has also been suggested. This study tested the hypothesis that ephedrine infusion with crystalloid loading at spinal anaesthesia would reduce hypotension and alter neonatal outcome compared with fluid preloading. One hundred and twenty women undergoing elective caesarean delivery were randomly allocated to one of three groups to receive rapid infusion of lactated Ringer's solution (20 ml.kg(-1), n=40) or 4% succinylated gelatin solution (500 ml, n =40) before spinal anaesthesia or an ephedrine infusion (1.25 mg.minute(-1)) plus lactated Ringer's solution (1000 ml, n=40) after spinal anaesthesia. The incidence of hypotension (moderate and severe) and the ephedrine dose used to treat hypotension were compared. Neonatal outcome was assessed using Apgar scores and umblical venous and arterial blood gas analysis. The frequency of moderate or severe hypotension was lower in the ephedrine group than in the crystalloid or colloid preload group (10% vs. 51% and 38%; 5% vs. 21% and 23% respectively, P < 0.05). The incidence of nausea was significantly different between the crystalloid preload and ephedrine group. Umbilical blood gas analysis and Apgar scores were similar in all groups. A combination of an ephedrine infusion at 1.25 mg.minute(-1) with a crystalloid co-load was more effective than fluid preloading with crystalloid or colloid in the prevention of moderate and severe hypotension.

  18. [Asymptomatic electrical myocardial necrosis during the infusion of betamimetics in status asthmaticus].

    PubMed

    Beauvoir, C; Sissman, J

    1988-01-01

    A case is reported of a 56 year old woman admitted for status asthmaticus. She had no known history of cardiovascular disease. During the infusion of salbutamol, there appeared signs of myocardial infarction on the ECG trace. The patient did not complain of any symptoms suggestive of myocardial infarction. Closer cardiac examination and ultrasound revealed features of hypertrophic cardiomyopathy. The first ECG carried out on admission was in fact in favour of this diagnosis. The pathogenesis of this myocardial infarction is discussed: the long lasting hypoxaemia and the tachycardia induced by the salbutamol simulated hard exercise, poorly tolerated by patients suffering from hypertrophic cardiomyopathy. Also, this type of cardiomyopathy is known to be associated with impaired myocardial vasodilator reserve and small vessel coronary artery disease.

  19. [Constant-infusion technique of inulin clearance without urine collection].

    PubMed

    Kamei, Koichi; Ito, Shuichi; Iijima, Kazumoto

    2011-01-01

    Inulin clearance is accepted as the gold standard for estimating the glomerular filtration rate (GFR). However, the method of this examination is troublesome and infants need difficult bladder catheterization. The existence of residual urine results in an inaccurate estimation of GFR and the proceduse requires a large amount of transfusion. In the plasma infusion method, inulin reaches an equilibrium in which the inulin urinary excretion rate is equal to the infusion rate, and urine collection is unnecessary. We estimated GFR in 21 children using both the plasma infusion method and renal infusion method. In the renal infusion method, the loading infusion of 1% inulin was administered over 30 minutes at the dose of 5 mL/kg body weight, followed by maintenance infusion at the constant speed (mL/hour) of 1.5 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/ 1.73. Three 30-minute urine collections were performed and the plasma inulin levels were measured to estimate GFR. In the plasma infusion method, maintenance infusion was conducted at the speed (mL/hour) of 0.6 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/1.73. The mean plasma inulin concentrations at 8, 9 and 10 hours were examined and GFR was calculated with the infusion rate. The GFRs for the renal infusion methods (Cin) and plasma infusion methods (e-Cin) were 91.90 +/- 39.61 and 95.33 +/- 38.08 mL/min/1.73 m2, respectively. The values for Cin and e-Cin showed good linear correlation (R2 = 0.81). The value of e-Cin/Cin was 1.069 +/- 0.172 and the mean e-Cin value was only 7% higher than that of Cin. We believe that GFR estimated by the constant infusion method shows a value approximating that estimated by the standard method. This technique is noninvasive for infants and the GFR of children who have vesicoureteral reflux or residual urine in the bladder can be estimated. The method does not need a large amount of transfusion and is suitable for children with heart failure. We believe that

  20. Effects of dietary manipulations and glucose infusion on glucagon response during exercise in rats.

    PubMed

    Tadjoré, M; Bergeron, R; Latour, M; Désy, F; Warren, C; Lavoie, J M

    1997-07-01

    The purpose of the present investigation was to test the hypothesis that blood glucose concentration is not always related to glucagon response during exercise. Three groups of rats were submitted to a prolonged (3-h) swimming exercise. Two groups of rats had their normal food intake restricted by 50% the night before the experiment. One of these two groups of rats was intravenously infused with glucose throughout exercise to maintain euglycemia. The third group of rats swam while under normal dietary conditions. Plasma glucose, sampled in arterial blood, was reduced (P < 0.05) at 75, 105, 150, and 170 min of exercise (from approximately 130 to 110 mg/dl) in the food-restricted animals without glucose infusion, whereas a significant (P < 0.05) increase was measured in the two other groups during exercise. A significant (P < 0.01) difference in the mean integrated areas under the glucose-concentration curve was found only between the fed and the two food-restricted groups. Plasma insulin concentrations decreased (P < 0.05) similarly in all groups during exercise, whereas plasma epinephrine and norepinephrine concentrations increased significantly (P < 0.01) in all groups. Despite differences between groups in plasma glucose response during exercise, and despite the absence of any decrease in exercising blood glucose levels in at least two of the three groups, plasma glucagon responses were increased (P < 0.05) similarly in all groups (from approximately 250 to 550 pg/ml) at the end of the exercise period. The increase in glucagon was significant after 90 min of exercise in the food-restricted groups, with or without glucose infusion, but only after 140 min in the fed group. These results indicate that the glucagon response during exercise is not always linked to the decrease in plasma glucose.

  1. Heterogeneous responses of human limbs to infused adrenergic agonists: a gravitational effect?

    NASA Technical Reports Server (NTRS)

    Pawelczyk, James A.; Levine, Benjamin D.

    2002-01-01

    Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures relative to the arms. We hypothesized that this "dependent hypertension" would be associated with altered adrenergic responsiveness. Isoproterenol (0.75-24 ng x 100 ml limb volume-1 x min-1) and phenylephrine (0.025-0.8 microg x 100 ml limb volume-1 x min-1) were infused incrementally in the brachial and femoral arteries of 12 normal volunteers; changes in limb blood flow were quantified by using strain-gauge plethysmography. Compared with the forearm, baseline calf vascular resistance was greater (38.8 +/- 2.5 vs. 26.9 +/- 2.0 mmHg x 100 ml x min x ml-1; P < 0.001) and maximal conductance was lower (46.1 +/- 11.9 vs. 59.4 +/- 13.4 ml x ml-1 x min-1 x mmHg-1; P < 0.03). Vascular conductance did not differ between the two limbs during isoproterenol infusions, whereas decreases in vascular conductance were greater in the calf than the forearm during phenylephrine infusions (P < 0.001). With responses normalized to maximal conductance, the half-maximal response for phenylephrine was significantly less for the calf than the forearm (P < 0.001), whereas the half-maximal response for isoproterenol did not differ between limbs. We conclude that alpha1- but not beta-adrenergic-receptor responsiveness in human limbs is nonuniform. The relatively greater response to alpha1-adrenergic-receptor stimulation in the calf may represent an adaptive mechanism that limits blood pooling and capillary filtration in the legs during standing.

  2. Constant infusion transpulmonary thermodilution for the assessment of cardiac output in exercising humans.

    PubMed

    Calbet, J A L; Mortensen, S P; Munch, G D W; Curtelin, D; Boushel, R

    2016-05-01

    To determine the accuracy and precision of constant infusion transpulmonary thermodilution cardiac output (CITT-Q) assessment during exercise in humans, using indocyanine green (ICG) dilution and bolus transpulmonary thermodilution (BTD) as reference methods, cardiac output (Q) was determined at rest and during incremental one- and two-legged pedaling on a cycle ergometer, and combined arm cranking with leg pedaling to exhaustion in 15 healthy men. Continuous infusions of iced saline in the femoral vein (n = 41) or simultaneously in the femoral and axillary (n = 66) veins with determination of temperature in the femoral artery were used for CITT-Q assessment. CITT-Q was linearly related to ICG-Q (r = 0.82, CITT-Q = 0.876 × ICG-Q + 3.638, P < 0.001; limits of agreement ranging from -1.43 to 3.07 L/min) and BTD-Q (r = 0.91, CITT-Q = 0.822 × BTD + 4.481 L/min, P < 0.001; limits of agreement ranging from -1.01 to 2.63 L/min). Compared with ICG-Q and BTD-Q, CITT-Q overestimated cardiac output by 1.6 L/min (≈ 10% of the mean ICG and BTD-Q values, P < 0.05). For Q between 20 and 28 L/min, we estimated an overestimation < 5%. The coefficient of variation of 23 repeated CITT-Q measurements was 6.0% (CI: 6.1-11.1%). In conclusion, cardiac output can be precisely and accurately determined with constant infusion transpulmonary thermodilution in exercising humans.

  3. Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients.

    PubMed

    Bienert, Agnieszka; Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz

    2010-06-01

    This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V(C) = 27.7 l, V(T) = 801 l, and CL(D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 x (1-0.00714 x (SBP-135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC(50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.

  4. Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients

    PubMed Central

    Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J.; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz

    2010-01-01

    This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were VC = 27.7 l, VT = 801 l, and CLD = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65·(1 − 0.00714·(SBP − 135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC50 equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light–dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night–day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients. PMID:20544262

  5. The analgesic efficacy of continuous presternal bupivacaine infusion through a single catheter after cardiac surgery

    PubMed Central

    Nasr, Dalia Abdelhamid; Abdelhamid, Hadeel Magdy; Mohsen, Mai; Aly, Ahmad Helmy

    2015-01-01

    Background: Median sternotomy, sternal spreading, and sternal wiring are the main causes of pain during the early recovery phase following cardiac surgery. Aim: This study was designed to evaluate the analgesic efficacy of continuous presternal bupivacaine infusion through a single catheter after parasternal block following cardiac surgery. Materials and Methods: The total of 40 patients (American Society of Anesthesiologist status II, III), 45–60 years old, undergoing coronary – artery bypass grafting were enrolled in this prospective, randomized, double-blind study. A presternal catheter was inserted with continuous infusion of 5 mL/h bupivacaine 0.25% (Group B) or normal saline (Group C) during the first 48 postoperative hrs. Primary outcomes were postoperative morphine requirements and pain scores, secondary outcomes were extubation time, postoperative respiratory parameters, incidence of wound infection, Intensive Care Unit (ICU) and hospital stay duration, and bupivacaine level in blood. Statistical Methods: Student's t-test was used to analyze the parametric data and Chi-square test for categorical variables. Results: During the postoperative 48 h, there was marked reduction in morphine requirements in Group B compared to Group C, (8.6 ± 0.94 mg vs. 18.83 ± 3.4 mg respectively, P = 0.2), lower postoperative pain scores, shorter extubation time (117 ± 10 min vs. 195 ± 19 min, respectively, P = 0.03), better respiratory parameters (PaO2/FiO2, PaCO2 and pH), with no incidence of wound infection, no differences in ICU or hospital stay duration. The plasma concentration of bupivacaine remained below the toxic threshold (at T24, 1.2 ug/ml ± 0.3 and T48 h 1.7 ± 0.3 ug/ml). Conclusion: Continuous presternal bupivacaine infusion has resulted in better postoperative analgesia, reduction in morphine requirements, shorter time to extubation, and better postoperative respiratory parameters than the control group. PMID:25566704

  6. [Central venous infusion of dopamine. Changes in dose during central venous pressure measurement].

    PubMed

    Guiglio, C; Haro, D; Muchada, R

    1993-01-01

    The changes in the doses of dopamine administered at a steady rate which occur during central venous pressure (CVP) measurement were studied. A workbench model with a single lumen central venous catheter was devised with which a mathematical model was constructed to calculate the alterations due to changes in different variables: central venous pressure, dopamine dose, collateral infusions. The average time for CVP measurement was 2 min. The volume of 5% glucose solution filling the manometer was 2.3 ml. The dopamine bolus generated by CVP measurement was equivalent to a dose of 85 micrograms.kg-1 x min-1. The delay required for a return to the initial dose was 2 h 42 min. Changes in CVP led to inversely proportional changes in dopamine dose. These also depended on the level to which the measuring tube was filled before carrying out the measurement. High initial rates of dopamine infusion required shorter times for a return to initial dopamine doses. The bolus and time for recovery were also inversely proportional to the volume of infusion fluids given at a steady rate on the same venous line. This model was tested in a patient suffering from bacterial pneumonia and septic shock (60 years, 55 kg). CVP measurement resulted in a bolus dose of 17 micrograms.kg-1 x min-1, leading to a 43% decrease in aortic flow rate and 60% in the ejection volume. After about 25 min, heart rate and mean arterial blood pressure had returned to their initial values, although aortic flow rate remained 30% below initial values. This problem is also met with other drugs, such as heparin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8338258

  7. Effects of pregnancy and magnesium sulfate infusion on blood pressure and plasma catecholamines.

    PubMed

    Lee, M I; Bottoms, S F; Sokol, R J

    1985-10-01

    Magnesium sulfate (MgSO4) infusion often lowers blood pressure, but the responsible mechanisms are not clear. Since catecholamines play a major role in blood pressure regulation, we studied the effects of MgSO4 infusion on blood pressure, pulse rate, and plasma catecholamines in late pregnant and in nonpregnant New Zealand white rabbits. Pregnancy was associated with higher levels of dopamine (P less than 0.01) and epinephrine (P less than 0.001). MgSO4 treatment decreased mean arterial pressure (P less than 0.001), increased pulse rate (P less than 0.01), decreased dopamine (P less than 0.01) and decreased epinephrine (P less than 0.001). No significant effect on norepinephrine levels was noted, and there was no evidence that the effect of MgSO4 treatment was influenced by pregnancy. Further investigation is needed to clarify the role of catecholamines in mediating the effects of pregnancy and MgSO4 treatment on blood pressure regulation.

  8. False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion

    SciTech Connect

    Smits, P.; Corstens, F.H.; Aengevaeren, W.R.; Wackers, F.J.; Thien, T. )

    1991-08-01

    The vasodilator effect of intravenously administered dipyridamole may be caused by an increase in endogenous plasma adenosine levels. The authors evaluated the effect of caffeine, an adenosine receptor antagonist, on the diagnostic results of dipyridamole-201Tl myocardial imaging in eight patients with coronary artery disease. Caffeine infusion significantly attenuated the dipyridamole-induced fall in blood pressure and the accompanied increase in heart rate. The infusion of dipyridamole alone resulted in chest pain and ST-segment depressions on the electrocardiogram in four patients, whereas none of these problems occurred when the tests were repeated after caffeine. In six of eight patients, caffeine was responsible for false-negative dipyridamole-201Tl tests. Semiquantitive scores of the dipyridamole-induced 201Tl perfusion defects were decreased by caffeine from 9.0 {plus minus} 0.9 to 2.0 {plus minus} 1.1 points (p less than 0.05). Computerized analysis revealed a caffeine-mediated reduction in the percent reversibility of the images from 46% {plus minus} 16% to 6% {plus minus} 10% (p less than 0.05). They conclude that the use of caffeinated products prior to dipyridamole-201Tl testing may be responsible for false-negative findings.

  9. Thallium scintigraphy during dobutamine infusion: nonexercise-dependent screening test for coronary disease

    SciTech Connect

    Mason, J.R.; Palac, R.T.; Freeman, M.L.; Virupannavar, S.; Loeb, H.S.; Kaplan, E.; Gunnar, R.M.

    1984-03-01

    Exercise thallium scintigraphy has proven to be a sensitive method for detecting coronary artery disease (CAD). However, early redistribution of thallium and inadequate exercise can reduce its sensitivity. In this study, dobutamine was infused in incremental doses (5, 10, 15, and 20 micrograms/kg/min) in 24 patients being evaluated for chest pain. Thallium scintigraphy was completed during the maximum dose of dobutamine tolerated and repeated 4 hours later. Significant CAD was present in 16 patients; the remaining eight had normal coronaries. Exercise ECG was obtained in 23 patients. During dobutamine thallium scintigraphy, reversible perfusion defects occurred in 15 of 16 CAD and in one of eight non-CAD patients, resulting in a sensitivity of 94% and a specificity of 87%. Exercise ECG had a sensitivity of 60% and a specificity of 63%. We conclude that: (1) dobutamine thallium scintigraphy appears to be a sensitive method for detecting significant CAD and provided a more sensitive screening test than exercise ECG; (2) dobutamine thallium scintigraphy is especially useful in patients who cannot exercise; and (3) because imaging occurs during dobutamine infusion, the problem of early redistribution may be mitigated.

  10. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  11. Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

    PubMed Central

    de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.

    2015-01-01

    Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552

  12. Bilateral accessory thoracodorsal artery.

    PubMed

    Natsis, Konstantinos; Totlis, Trifon; Tsikaras, Prokopios; Skandalakis, Panagiotis

    2006-09-01

    The subscapular artery arises from the third part of the axillary artery and gives off the circumflex scapular and the thoracodorsal arteries. Although anatomical variations of the axillary artery are very common, the existence of a unilateral accessory thoracodorsal artery has been described in the literature only once. There are no reports of bilateral accessory thoracodorsal artery, in the literature. In the present study, a bilateral accessory thoracodorsal artery, originating on either side of the third part of the axillary artery, is described in a 68-year-old female cadaver. All the other branches of the axillary artery had a typical origin, course, distribution and termination. This extremely rare anatomical variation apart from the anatomical importance also has clinical significance for surgeons in this area. Especially, during the dissection or mobilization of the latissimus dorsi that is partly used for coverage problems in many regions of the body and also in dynamic cardiomyoplasty, any iatrogenic injury of this accessory artery may result in ischemia and functional loss of the graft.

  13. Urokinase-type plasminogen activator deficiency has little effect on seizure susceptibility and acquired epilepsy phenotype but reduces spontaneous exploration in mice.

    PubMed

    Rantala, J; Kemppainen, S; Ndode-Ekane, X E; Lahtinen, L; Bolkvadze, Tamuna; Gurevicius, K; Tanila, H; Pitkänen, A

    2015-01-01

    Urokinase-type plasminogen activator (uPA), a serine protease, converts plasminogen to plasmin. Activation of plasmin leads to degradation of the extracellular matrix, which is critical for tissue recovery, angiogenesis, cell migration, and axonal and synaptic plasticity. We hypothesized that uPA deficiency would cause an abnormal neurophenotype and would lead to exacerbated epileptogenesis after brain injury. Wild-type (Wt) and uPA-/- mice underwent a battery of neurologic behavioral tests evaluating general reactivity, spontaneous exploratory activity, motor coordination, pain threshold, fear and anxiety, and memory. We placed particular emphasis on the effect of uPA deficiency on seizure susceptibility, including the response to convulsants (pentylenetetrazol, kainate, or pilocarpine) and kainate-induced epileptogenesis and epilepsy. The uPA-/- mice showed no motor or sensory impairment compared with the Wt mice. Hippocampus-dependent spatial memory also remained intact. The uPA-/- mice, however, exhibited reduced exploratory activity and an enhanced response to a tone stimulus (p<0.05 compared with the Wt mice). The urokinase-type plasminogen activator deficient mice showed no increase in spontaneous or evoked epileptiform electrographic activity. Rather, the response to pilocarpine administration was reduced compared with the Wt mice (p<0.05). Also, the epileptogenesis and the epilepsy phenotype after intrahippocampal kainate injection were similar to those in the Wt mice. Taken together, uPA deficiency led to diminished interest in the environmental surroundings and enhanced emotional reactivity to unexpected aversive stimuli. Urokinase-type plasminogen activator deficiency was not associated with enhanced seizure susceptibility or worsened poststatus epilepticus epilepsy phenotype.

  14. Local release of ATP into the arterial inflow and venous drainage of human skeletal muscle: insight from ATP determination with the intravascular microdialysis technique.

    PubMed

    Mortensen, Stefan P; Thaning, Pia; Nyberg, Michael; Saltin, Bengt; Hellsten, Ylva

    2011-04-01

    Intraluminal ATP could play an important role in the local regulation of skeletal muscle blood flow, but the stimuli that cause ATP release and the levels of plasma ATP in vessels supplying and draining human skeletal muscle remain unclear. To gain insight into the mechanisms by which ATP is released into plasma, we measured plasma [ATP] with the intravascular microdialysis technique at rest and during dynamic exercise (normoxia and hypoxia), passive exercise, thigh compressions and arterial ATP, tyramine and ACh infusion in a total of 16 healthy young men. Femoral arterial and venous [ATP] values were 109 ± 34 and 147 ± 45 nmol l(−1) at rest and increased to 363 ± 83 and 560 ± 111 nmol l(−1), respectively, during exercise (P < 0.05), whereas these values did not increase when exercise was performed with the other leg. Hypoxia increased venous plasma [ATP] at rest compared to normoxia (P < 0.05), but not during exercise. Arterial ATP infusion (≤1.8 μmol min(−1) increased arterial plasma [ATP] from 74 ± 17 to 486 ± 82 nmol l(−1) (P < 0.05), whereas it remained unchanged in the femoral vein at ∼150 nmol l(−1). Both arterial and venous plasma [ATP] decreased during acetylcholine infusion (P < 0.05). Rhythmic thigh compressions increased arterial and venous plasma [ATP] compared to baseline conditions, whereas these values did not change during passive exercise or tyramine infusion. These results demonstrate that ATP is released locally into arterial and venous plasma during exercise and during hypoxia at rest. Compression of the vascular system could contribute to the increase during exercise whereas there appears to be little ATP release in response to increased blood flow, vascular stretch or sympathetic ATP release. Furthermore, the half-life of arterially infused ATP is <1 s. PMID:21300753

  15. Local release of ATP into the arterial inflow and venous drainage of human skeletal muscle: insight from ATP determination with the intravascular microdialysis technique

    PubMed Central

    Mortensen, Stefan P; Thaning, Pia; Nyberg, Michael; Saltin, Bengt; Hellsten, Ylva

    2011-01-01

    Abstract Intraluminal ATP could play an important role in the local regulation of skeletal muscle blood flow, but the stimuli that cause ATP release and the levels of plasma ATP in vessels supplying and draining human skeletal muscle remain unclear. To gain insight into the mechanisms by which ATP is released into plasma, we measured plasma [ATP] with the intravascular microdialysis technique at rest and during dynamic exercise (normoxia and hypoxia), passive exercise, thigh compressions and arterial ATP, tyramine and ACh infusion in a total of 16 healthy young men. Femoral arterial and venous [ATP] values were 109 ± 34 and 147 ± 45 nmol l−1 at rest and increased to 363 ± 83 and 560 ± 111 nmol l−1, respectively, during exercise (P < 0.05), whereas these values did not increase when exercise was performed with the other leg. Hypoxia increased venous plasma [ATP] at rest compared to normoxia (P < 0.05), but not during exercise. Arterial ATP infusion (≤1.8 μmol min−1) increased arterial plasma [ATP] from 74 ± 17 to 486 ± 82 nmol l−1 (P < 0.05), whereas it remained unchanged in the femoral vein at ∼150 nmol l−1. Both arterial and venous plasma [ATP] decreased during acetylcholine infusion (P < 0.05). Rhythmic thigh compressions increased arterial and venous plasma [ATP] compared to baseline conditions, whereas these values did not change during passive exercise or tyramine infusion. These results demonstrate that ATP is released locally into arterial and venous plasma during exercise and during hypoxia at rest. Compression of the vascular system could contribute to the increase during exercise whereas there appears to be little ATP release in response to increased blood flow, vascular stretch or sympathetic ATP release. Furthermore, the half-life of arterially infused ATP is <1 s. PMID:21300753

  16. Chronic postthoracotomy pain and perioperative ketamine infusion.

    PubMed

    Hu, Jie; Liao, Qin; Zhang, Fan; Tong, Jianbin; Ouyang, Wen

    2014-06-01

    The objectives of this study were to investigate whether continuous intravenous ketamine during the first 72 hours after thoracotomy could reduce the incidence and intensity of chronic postthoracotomy pain (CPTP) and to define the incidence and risk factors of CPTP. Seventy-eight patients receiving thoracotomy for lung tumor (benign or malignant) were randomly divided into two groups: ketamine group (n = 31) and control groups (n = 47). Patients in the ketamine group received intravenous ketamine 1 mg/kg before incision, followed by 2 μg/kg/minute infusion for 72 hours plus sufentanil patient-controlled intravenous analgesia after thoracotomy. Patients in the control group received intravenous a 0.9% normal saline and infusion plus sufentanil patient-controlled intravenous analgesia. The solutions patients received were blinded. The numerical rating scale (NRS) pain scores and the incidence and risk factors of CPTP were recorded during the first 6 months after surgery. Compared with control group, the incidence of chronic pain in the ketamine group did not decrease at 2 months (χ(2) = 1.599, P = .206) and 6 months (χ(2) = 0.368, P = .544) after surgery. Postoperative pain scores in the ketamine group were not significantly different from those of the control group patients at 2 months (U = 677.5, P = .593) and 6 months (U = 690.5, P = .680). The incidence of CPTP was 78.2% (61/78) at 2 months and 53.8% (42/78) at 6 months after surgery. Retractor used time (OR = 5.811, P = .002), inadequate acute pain control (NRS ≥ 5) (OR = 5.425, P = .048), and chemotherapy (OR = 3.784, P = .056) were independent risk factors for chronic postthoracotomy pain. The authors conclude that continuous intravenous ketamine (2 μg/kg/min) during the first 72 hours after thoracotomy was not beneficial to prevent chronic postthoracotomy pain. The independent risk factors for chronic postthoracotomy pain were retractor used time, inadequate acute pain control, and chemotherapy.

  17. Pre-rigor infusion with kiwifruit juice improves lamb tenderness.

    PubMed

    Han, J; Morton, J D; Bekhit, A E D; Sedcole, J R

    2009-07-01

    The ability of pre-rigor infusion of kiwifruit juice to improve the tenderness of lamb was investigated. Lamb carcasses were infused (10% body weight) with fresh kiwifruit juice (Ac), water (W) and a non-infusion control (C) treatment. Infusion treatment had no effect on lamb hot carcass weight, cold carcass weight and chilling evaporative losses. The infused treatment carcasses of Ac and W had lower (P<0.05) pH values than C carcasses during the initial 12h post-mortem. The LD muscles from Ac carcasses were more tender with significantly lower shear force (P<0.001) compared with C and W carcasses during the six days following infusion with the kiwifruit juice. The enhanced proteolytic activity (P=0.002) resulting from the infused kiwifruit juice in Ac carcasses was associated with significant degradation of the myofibrillar proteins, appearance of new peptides and activation of m-calpain during post-mortem ageing. Thus, kiwifruit juice is powerful and easily prepared meat tenderizer, which could contribute efficiently and effectively to the meat tenderization process. PMID:20416722

  18. Systemic response to low-dose endotoxin infusion in cats.

    PubMed

    DeClue, Amy E; Williams, Kurt J; Sharp, Claire; Haak, Carol; Lechner, Elizabeth; Reinero, Carol R

    2009-12-15

    Sepsis is a common problem in feline patients and is associated with substantial morbidity and mortality. There has been little research investigating the physiologic response to bacterial infection in cats, in part because appropriate models have not been developed. The objective of this study was to characterize the response to low-dose LPS infusion in conscious, healthy cats. Measures of systemic inflammation, hemodynamic stability, coagulation, metabolic function, and organ damage were compared between placebo and low-dose LPS infusion (2mcg/kg/hx4h, IV) in cats, with each cat serving as its own control. Markers of systemic inflammation including temperature, plasma TNF activity, IL-6, CXCL-8 and IL-10 concentrations were significantly increased and white blood cell counts were significantly decreased after LPS infusion. A biphasic hypotensive response was observed after initiation of LPS infusion without concurrent tachycardia. Additionally, LPS administration significantly increased blood glucose, lactate and creatinine concentrations. Patchy alveolar congestion, multifocal acute alveolar epithelial necrosis, and mild pulmonary edema were noted in the lungs along with acute centrilobular hepatocellular necrosis, and mild lymphocyte apoptosis in the spleen and/or intestinal Peyer's patches. No biologically significant alterations in coagulation parameters developed after LPS infusion. Low-dose LPS infusion in cats induced systemic inflammation, hemodynamic derangement, metabolic alterations and mild organ damage. Low-dose endotoxin infusion is a viable pre-clinical model to study naturally developing sepsis in cats.

  19. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism.

    PubMed

    Galindo, C; Larsen, M; Ouellet, D R; Maxin, G; Pellerin, D; Lapierre, H

    2015-11-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate (BHBA) in postpartum dairy cows according to a generalized randomized incomplete block design with repeated measures in time. At calving, cows were blocked according to parity (second and third or greater) and were allocated to 2 treatments: abomasal infusion of water (n=4) or abomasal infusion of free AA with casein profile (AA-CN; n=5) in addition to the same basal diet. The AA-CN infusion started with half the maximal dose at 1 d in milk (DIM) and then steadily decreased from 791 to 226 g/d from DIM 2 to 29 to cover the estimated essential AA deficit. On DIM 5, 15, and 29, D[6,6-(2)H2]-glucose (23.7 mmol/h) was infused into a jugular vein for 5h, and 6 blood samples were taken from arterial, portal, hepatic, and mammary sources at 45-min intervals, starting 1h after the initiation of the D[6,6-(2)H2]glucose infusion. Trans-organ fluxes were calculated as veno-arterial differences times plasma flow (splanchnic: downstream dilution of deacetylated para-aminohippurate; mammary: Fick principle using Phe+Tyr). Energy-corrected milk and lactose yields increased on average with AA-CN by 6.4 kg/d and 353 g/d, respectively, with no DIM × treatment interaction. Despite increased AA supply and increased demand for lactose secretion with AA-CN, net hepatic release of glucose remained unchanged, but WB-Ra of glucose tended to increase with AA-CN. Portal true flux of glucose increased with AA-CN and represented, on average, 17% of WB-Ra. Splanchnic true flux of glucose was unaltered by treatments and was numerically equivalent to WB-Ra, averaging 729 and 741 mmol/h, respectively. Mammary glucose utilization increased with AA-CN infusion, averaging 78% of WB-Ra, and increased

  20. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism.

    PubMed

    Galindo, C; Larsen, M; Ouellet, D R; Maxin, G; Pellerin, D; Lapierre, H

    2015-11-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate (BHBA) in postpartum dairy cows according to a generalized randomized incomplete block design with repeated measures in time. At calving, cows were blocked according to parity (second and third or greater) and were allocated to 2 treatments: abomasal infusion of water (n=4) or abomasal infusion of free AA with casein profile (AA-CN; n=5) in addition to the same basal diet. The AA-CN infusion started with half the maximal dose at 1 d in milk (DIM) and then steadily decreased from 791 to 226 g/d from DIM 2 to 29 to cover the estimated essential AA deficit. On DIM 5, 15, and 29, D[6,6-(2)H2]-glucose (23.7 mmol/h) was infused into a jugular vein for 5h, and 6 blood samples were taken from arterial, portal, hepatic, and mammary sources at 45-min intervals, starting 1h after the initiation of the D[6,6-(2)H2]glucose infusion. Trans-organ fluxes were calculated as veno-arterial differences times plasma flow (splanchnic: downstream dilution of deacetylated para-aminohippurate; mammary: Fick principle using Phe+Tyr). Energy-corrected milk and lactose yields increased on average with AA-CN by 6.4 kg/d and 353 g/d, respectively, with no DIM × treatment interaction. Despite increased AA supply and increased demand for lactose secretion with AA-CN, net hepatic release of glucose remained unchanged, but WB-Ra of glucose tended to increase with AA-CN. Portal true flux of glucose increased with AA-CN and represented, on average, 17% of WB-Ra. Splanchnic true flux of glucose was unaltered by treatments and was numerically equivalent to WB-Ra, averaging 729 and 741 mmol/h, respectively. Mammary glucose utilization increased with AA-CN infusion, averaging 78% of WB-Ra, and increased

  1. Angioplasty and stent placement - peripheral arteries - discharge

    MedlinePlus

    Percutaneous transluminal angioplasty - peripheral artery - discharge; PTA - peripheral artery - discharge; Angioplasty - peripheral artery - discharge; Balloon angioplasty - peripheral artery- discharge; PAD - PTA discharge; PVD - ...

  2. alpha-2 Macroglobulin receptor/Ldl receptor-related protein(Lrp)- dependent internalization of the urokinase receptor

    PubMed Central

    1995-01-01

    The GPI-anchored urokinase plasminogen activator receptor (uPAR) does not internalize free urokinase (uPA). On the contrary, uPAR-bound complexes of uPA with its serpin inhibitors PAI-1 (plasminogen activator inhibitor type-1) or PN-1 (protease nexin-1) are readily internalized in several cell types. Here we address the question whether uPAR is internalized as well upon binding of uPA-serpin complexes. Both LB6 clone 19 cells, a mouse cell line transfected with the human uPAR cDNA, and the human U937 monocytic cell line, express in addition to uPAR also the endocytic alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP/alpha 2-MR) which is required to internalize uPAR-bound uPA-PAI-1 and uPA-PN-1 complexes. Downregulation of cell surface uPAR molecules in U937 cells was detected by cytofluorimetric analysis after uPA-PAI-1 and uPA-PN-1 incubation for 30 min at 37 degrees C; this effect was blocked by preincubation with the ligand of LRP/alpha 2-MR, RAP (LRP/alpha 2-MR- associated protein), known to block the binding of the uPA complexes to LRP/alpha 2-. MR. Downregulation correlated in time with the intracellular appearance of uPAR as assessed by confocal microscopy and immuno-electron microscopy. After 30 min incubation with uPA-PAI-1 or uPA-PN-1 (but not with free uPA), confocal microscopy showed that uPAR staining in permeabilized LB6 clone 19 cells moved from a mostly surface associated to a largely perinuclear position. This effect was inhibited by the LRP/alpha 2-MR RAP. Perinuclear uPAR did not represent newly synthesized nor a preexisting intracellular pool of uPAR, since this fluorescence pattern was not modified by treatment with the protein synthesis inhibitor cycloheximide, and since in LB6 clone 19 cells all of uPAR was expressed on the cell surface. Immuno-electron microscopy confirmed the plasma membrane to intracellular translocation of uPAR, and its dependence on LRP/alpha 2-MR in LB6 clone 19 cells only after

  3. Inhibition of urokinase plasminogen activator “uPA” activity alters ethanol consumption and conditioned place preference in mice

    PubMed Central

    Al Maamari, Elyazia; Al Ameri, Mouza; Al Mansouri, Shamma; Bahi, Amine

    2014-01-01

    Urokinase plasminogen activator, uPA, is a serine protease implicated in addiction to drugs of abuse. Using its specific inhibitor, B428, we and others have characterized the role of uPA in the rewarding properties of psychostimulants, including cocaine and amphetamine, but none have examined the role of uPA in ethanol use disorders. Therefore, in the current study, we extended our observations to the role of uPA in ethanol consumption and ethanol-induced conditioned place preference. The general aim of the present series of experiments was to investigate the effects of the administration of the B428 on voluntary alcohol intake and ethanol conditioned reward. A two-bottle choice, unlimited-access paradigm was used to compare ethanol intake between vehicle- and 3, 10, and 30 mg/kg B428-administered mice. For this purpose, the mice were presented with an ethanol solution (2.5%–20%) and water, at each concentration for 4 days, and their consumption was measured daily. Consumption of saccharin and quinine solutions was also measured. Systemic administration of B428 dose-dependently decreased ethanol intake and preference. Additionally, B428 mice did not differ from vehicle mice in their intake of graded solutions of tastants, suggesting that the uPA inhibition did not alter taste function. Also, ethanol metabolism was not affected following B428 injection. More importantly, 1.5 g/kg ethanol-induced conditioned place preference acquisition was blocked following B428 administration. Taken together, our results are the first to implicate uPA inhibition in the regulation of ethanol consumption and preference, and suggest that uPA may be considered as a possible therapeutic drug target for alcoholism and abstinence. PMID:25258509

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

    PubMed

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

    2015-01-01

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

  5. Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer.

    PubMed Central

    Solomayer, E. F.; Diel, I. J.; Wallwiener, D.; Bode, S.; Meyberg, G.; Sillem, M.; Gollan, C.; Kramer, M. D.; Krainick, U.; Bastert, G.

    1997-01-01

    Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases. Images Figure 1 PMID:9310251

  6. Flow cytometry evaluation of urokinase-type plasminogen activator receptor (UPA-R) in acute myeloid leukemia cells.

    PubMed

    Castagnari, B; Moretti, S; Latorraca, A; Rigolin, G M; Balsamo, R; Lanza, F; Castoldi, G L

    1995-01-01

    The aim of this study was to investigate by flow cytometry the expression of the UPA-R (Urokinase type plasminogen activator receptor-CD87) on the blastic population of AML and ALL patients in order to evaluate whether the presence of this molecule could be associated with peculiar clinical and biologic features of leukemic cells. Five different monoclonal antibodies (MoAbs) (clones: 3B10#; VIM5*; 109#; 68#; 100#) were used in order to detect the distinct forms of this cellular receptor. Cell reactivity varied significantly from case to case, also depending on the MoAb used for the flow cytometry analysis. In brief, 3B10# and VIM5* MoAbs were found to be positive in more than 90% of monocytes and neutrophils from healthy subjects, while the number of positive cells was decreased (60%) using the 109# MoAb. However, either 68# and 100# MoAbs recognised only a low number of blood monocytes and neutrophils (8-20%), while lymphocytes were unreactive with all the five UPA-R MoAbs. ALL cells were found to be CD87 negative in all cases. Blasts from AML showed a heterogeneous pattern of expression for the UPA-R MoAbs, being the reactivity strictly dependent on the MoAb used, and, to a higher extent, on the degree and type of maturation of the blastic cells. The number of blasts recognising 3B10# and VIM5* MoAbs was significantly higher than that reacting with the remaining MoAbs irrespective of the FAB subtype. Since proteolytic enzymes, like UPA, play a key role in the dissolution of the extracellular matrix, and in facilitating the cell egress from the bone marrow, it is conceivable that the expression of the UPA-R could contribute to the invasive properties and, possibly, metastatic potential of leukemic cells. PMID:8519488

  7. Thrombosis recanalization by paeoniflorin through the upregulation of urokinase-type plasminogen activator via the MAPK signaling pathway

    PubMed Central

    YE, SONGSHAN; MAO, BINGYU; YANG, LEI; FU, WEIYUN; HOU, JUNRAN

    2016-01-01

    Paeoniflorin, the major component of Paeonia lactiflora pall, has previously been reported to prevent thrombosis. Plasminogen activator urokinase (uPA) is a serine protease that markedly facilitates normal thrombosis resolution. Paeoniflorin and uPA have been linked to the mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, the influence of paeoniflorin on the expression of uPA was investigated and the underlying regulatory mechanism was preliminarily determined. The prothrombotic state of the model animals treated with paeoniflorin were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, the cytotoxicity of paeoniflorin on human umbilical vein endothelial cell (HUVEC) cultures was estimated using a methyl thiazolyl tetrazolium assay and the possible pathways involved in the interaction between paeoniflorin and uPA were evaluated using western blot analysis. The ELISA results demonstrated that the levels of 6-keto prostaglandin F1a, fibronectin and uPA were significantly upregulated by treatment with paeoniflorin compared with control (P<0.05). By contrast, the expression of fibrinogen, D-dimer and thromboxane B2 were inhibited. With an increase in the concentration of paeoniflorin the cell viability of HUVECs decreased gradually. The results of western blot analysis demonstrated that paeoniflorin increased the phosphorylation of MAPK 14 (p38) and MAPK 8 (JNK). The present study demonstrated that paeoniflorin has the potential to improve the prethrombotic state and recanalize thrombosis by increasing the expression of uPA, which may be mediated via regulation of the p38 and JNK MAPK signaling pathways. However, this treatment effect was dependent on the concentration of paeoniflorin used, an unsuitable concentration of the agent would result in a negative effect on the anti-thrombosis pathways. PMID:27082639

  8. Plasma Soluble Urokinase Receptor Level Is Correlated with Podocytes Damage in Patients with IgA Nephropathy

    PubMed Central

    Zhao, Yanfeng; Liu, Lijun; Huang, Jing; Shi, Sufang; Lv, Jicheng; Liu, Gang; Zhao, Minghui; Zhang, Hong

    2015-01-01

    Background Focal segmental glomerulosclerosis (FSGS) lesions are similar in characteristics to S lesions of the Oxford classification of IgA nephropathy (IgAN) and may predict poor prognosis. In the present study, we aimed to explore the association between plasma soluble urokinase receptor (suPAR) levels and S lesions and podocytes damage in IgAN patients. Methods We enrolled 569 IgAN patients with follow-up data and detected plasma suPAR levels at renal biopsy by enzyme-linked immunosorbent assay. Results Plasma suPAR levels in IgAN patients with or without S lesions did not differ significantly (P = 0.411). However, suPAR levels were positively correlated with proteinuria (r = 0.202, P < 0.001), and negatively correlated with estimated glomerular filtration rate (eGFR, r = –0.236, P < 0.001). In the partial correlation to adjust for eGFR, plasma suPAR levels remained positively correlated with proteinuria (r = 0.112, P = 0.023). In a Cox proportional hazards model, higher levels of plasma suPAR were not associated with poor renal outcome. Plasma suPAR levels of IgAN and primary FSGS patients with nephrotic syndrome were not significantly different (P = 0.306). Plasma suPAR levels in patients with extensive effacement of the epithelial cell foot processes of glomerular podocytes were significantly higher than those with segmental effacement on the basis of comparable eGFR (P = 0.036). Conclusions In IgAN patients, plasma suPAR levels were not associated with S lesions. However, they were positively associated with proteinuria and negatively associated with eGFR. In addition, plasma suPAR levels were positively associated with the effacement degree of the foot processes, which might partially contribute to the development of proteinuria in patients with IgAN. PMID:26167688

  9. Use of adenosine echocardiography for diagnosis of coronary artery disease

    SciTech Connect

    Zoghbi, W.A. )

    1991-07-01

    Two-dimensional echocardiography combined with exercise is sensitive and specific in the detection of coronary artery disease (CAD) by demonstrating transient abnormalities in wall motion. Frequently, however, patients cannot achieve maximal exercise because of various factors. Pharmacologic stress testing with intravenous adenosine was evaluated as a means of detecting CAD in a noninvasive manner. Patients with suspected CAD underwent echocardiographic imaging and simultaneous thallium 201 single-photon emission computed tomography during the intravenous administration of 140 micrograms/kg/min of adenosine. An increase in heart rate, decrease in blood pressure, and increase in double product were observed during adenosine administration. Initial observations revealed that wall motion abnormalities were induced by adenosine in areas of perfusion defects. The adenosine infusion was well tolerated, and symptoms disappeared within 1 to 2 minutes after termination of the infusion. Therefore preliminary observations suggest that adenosine echocardiography appears to be useful in the assessment of CAD.

  10. [The development of multifunction intravenous infusion quantitative packaging device].

    PubMed

    Zhao, Shufang; Li, Ruihua; Shen, Lianhong

    2012-11-01

    Aimed at tackling the compatibility issues arising from the drug reaction in intravenous infusion tube, we developed a simple, suitable and multi-function intravenous infusion tube for the special use for rescuing critical patients, the elderly, children etc. Each drug in a transfusion process can be filtered to realize quantitative packet and packet delivery. Thus, the drugs in the infusion tube are prevented from meeting with each other. No overlap, no particle pollution occurred. Stable performance and accurate dosage are maintained. As a result safety is ensured during drug delivery. PMID:23461118

  11. Acid-Base Homeostasis: Overview for Infusion Nurses.

    PubMed

    Masco, Natalie A

    2016-01-01

    Acid-base homeostasis is essential to normal function of the human body. Even slight alterations can significantly alter physiologic processes at the tissue and cellular levels. To optimally care for patients, nurses must be able to recognize signs and symptoms that indicate deviations from normal. Nurses who provide infusions to patients-whether in acute care, home care, or infusion center settings-have a responsibility to be able to recognize the laboratory value changes that occur with the imbalance and appreciate the treatment options, including intravenous infusions. PMID:27598068

  12. The Variable Rate Intravenous Insulin Infusion Protocol.

    PubMed

    Collard, Benjamin; Sturgeon, Jonathan; Patel, Natasha; Asharia, Shabbar

    2014-01-01

    Insulin use among inpatients is high and associated with severe and regular medication errors. An initial baseline audit showed a wide variation in the prescription of intravenous insulin within the trust. These included variation in the choice of fluid prescribed, electrolyte levels not consistently checked, handwritten illegible prescriptions, and varying parameters set for adjustment of the prescription. A Variable Rate Intravenous Insulin Infusion protocol (VRIII)) was introduced to standardize intravenous insulin prescription throughout the trust by all members of the clinical team. We looked at and measured uptake and effects of the VRIII protocol in improving standardization of insulin prescription for inpatients on insulin at St George's NHS trust. The protocol was uploaded to the intranet to allow access 24 hours a day and the staff educated about it. The VRIII protocol was routinely used successfully throughout the trust. Any initial problems were addressed through education of clinical staff. The protocol has shown decreased prescribing and administrative errors, whilst demonstrating good glucose and electrolyte control. Use of a standardized protocol helps reduce medication errors and demonstrates good glycaemic control. Regular and continued education of clinical staff is necessary to maintain its efficacy. PMID:26734228

  13. Intravitreal methotrexate infusion for proliferative vitreoretinopathy

    PubMed Central

    Sadaka, Ama; Sisk, Robert A; Osher, James M; Toygar, Okan; Duncan, Melinda K; Riemann, Christopher D

    2016-01-01

    Purpose The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI) during pars plana vitrectomy (PPV) for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR). Methods Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review. Results Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22) or a history of severe inflammation associated with high PVR risk (n=7) received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66%) and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%). At the last follow-up examination, the retinas of 26 of 29 eyes (90%) remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10%) developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months. Conclusion Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series. PMID:27698550

  14. [Clinical experimental studies of postoperative infusion analgesia].

    PubMed

    Dick, W; Knoche, E; Grundlach, G; Klein, I

    1983-06-01

    30 postoperative patients, who had undergone abdominal gynaecological surgery with standard general anaesthesia were randomly divided into three groups and received, in the recovery ward, a continuous infusion of either pentazocine, piritramid, or ketamine. The patients rated their pain on a 15 cm pain analogue score. Group I pentazocine: Mean dosage on the day of operation 0.12 mg/kg/h, 0.1 mg/kg/h on the first and only 0.07 mg/kg/h on the second postoperative day. Pentazocine blood levels were on average 50 micrograms/l. Group II piritramid: Mean dosage on the day of operation 0.038 mg/kg/h, 0.024 mg/kg/h on the first and 0.019 mg/kg/h on the second postoperative day. Blood levels of piritramid were not determined because there is no satisfactory assay available. Group III ketamine: mean dosage on the day of operation 0.32 mg/kg/h, 0.28 mg/kg/h on the first and 0.29 mg/kg/h on the second postoperative day. Ketamine blood levels lay between 120 and 180 micrograms/l. The three analgesics did not cause any important haemodynamic or respiratory side effects. Pentazocine and piritramid were the most effective analgesics, ketamine was the least effective with a high incidence of side effects. PMID:6412586

  15. Clinical experimental studies of postoperative infusion analgesia.

    PubMed

    Knoche, E; Dick, W; Bowdler, I; Gundlach, G

    1983-01-01

    Thirty postoperative patients, after undergoing abdominal hysterectomy and standard general anesthesia, were randomly allocated to three groups and received, in the recovery ward, a continuous infusion of either pentazocine, piritramide, or ketamine. The patients rated their pain on a 15-cm visual analog scale. Patients in group 1 received pentazocine. Mean dosage was 0.12 mg/kg/hr on the day of operation, 0.1 mg/kg/hr on the first postoperative day, and only 0.07 mg/kg/hr on the second postoperative day. Pentazocine blood levels averaged 50 micrograms/L. Patients in group 2 received piritramide. Mean dosage was 0.038 mg/kg/hr on the day of operation, 0.024 mg/kg/hr on the first postoperative day, and 0.019 mg/kg/hr on the second postoperative day. Blood levels of piritramide were not determined because no satisfactory assay is available. Patients in group 3 received ketamine. Mean dosage was 0.32 mg/kg/hr on the day of operation, 0.28 mg/kg/hr on the first postoperative day, and 0.29 mg/kg/hr on the second postoperative day. Ketamine blood levels ranged between 120 and 180 micrograms/L. None of the three analgesics caused any important hemodynamic or respiratory side effects. Pentazocine and piritramide were more effective analgesics than ketamine was. Ketamine also had a higher incidence of side effects. PMID:6627285

  16. Intravitreal methotrexate infusion for proliferative vitreoretinopathy

    PubMed Central

    Sadaka, Ama; Sisk, Robert A; Osher, James M; Toygar, Okan; Duncan, Melinda K; Riemann, Christopher D

    2016-01-01

    Purpose The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI) during pars plana vitrectomy (PPV) for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR). Methods Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review. Results Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22) or a history of severe inflammation associated with high PVR risk (n=7) received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66%) and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%). At the last follow-up examination, the retinas of 26 of 29 eyes (90%) remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10%) developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months. Conclusion Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series.

  17. Enhanced notification of infusion pump programming errors.

    PubMed

    Evans, R Scott; Carlson, Rick; Johnson, Kyle V; Palmer, Brent K; Lloyd, James F

    2010-01-01

    Hospitalized patients receive countless doses of medications through manually programmed infusion pumps. Many medication errors are the result of programming incorrect pump settings. When used appropriately, smart pumps have the potential to detect some programming errors. However, based on the current use of smart pumps, there are conflicting reports on their ability to prevent patient harm without additional capabilities and interfaces to electronic medical records (EMR). We developed a smart system that is connected to the EMR including medication charting that can detect and alert on potential pump programming errors. Acceptable programming limits of dose rate increases in addition to initial drug doses for 23 high-risk medications are monitored. During 22.5 months in a 24 bed ICU, 970 alerts (4% of 25,040 doses, 1.4 alerts per day) were generated for pump settings programmed outside acceptable limits of which 137 (14%) were found to have prevented potential harm. Monitoring pump programming at the system level rather than the pump provides access to additional patient data in the EMR including previous dosage levels, other concurrent medications and caloric intake, age, gender, vitals and laboratory results.

  18. Superior mesenteric artery syndrome.

    PubMed Central

    Ahmed, A. R.; Taylor, I.

    1997-01-01

    Superior mesenteric artery syndrome is a rare and controversial form of upper intestinal obstruction in which the third part of the duodenum is compressed by the overlying superior mesenteric artery. Any disease process decreasing the angle between the superior mesenteric artery and the abdominal aorta can result in the external compression of the duodenum and subsequent intestinal obstruction. The aetiology, presentation, investigation and management of this unusual condition are discussed. PMID:9497945

  19. [Popliteal artery entrapment syndrome].

    PubMed

    Musumeci, S; Iuppa, A; Beneventano, G; Rinella, P; Mammano, M; Cinquegrani, E

    1986-12-15

    Trapped popliteal artery syndrome is relatively uncommon: the literature reports some 60 cases. The clinical picture is linked to compression of the popliteal artery by the gastrocnemius as it contracts, thus distorting the arterial route. The result is an interruption in the blood flow distally to the area involved due to stenosis of the blood vessel that is at first functional but becomes organic. PMID:3808379

  20. Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy.

    PubMed

    Cossu, Giulio; Previtali, Stefano C; Napolitano, Sara; Cicalese, Maria Pia; Tedesco, Francesco Saverio; Nicastro, Francesca; Noviello, Maddalena; Roostalu, Urmas; Natali Sora, Maria Grazia; Scarlato, Marina; De Pellegrin, Maurizio; Godi, Claudia; Giuliani, Serena; Ciotti, Francesca; Tonlorenzi, Rossana; Lorenzetti, Isabella; Rivellini, Cristina; Benedetti, Sara; Gatti, Roberto; Marktel, Sarah; Mazzi, Benedetta; Tettamanti, Andrea; Ragazzi, Martina; Imro, Maria Adele; Marano, Giuseppina; Ambrosi, Alessandro; Fiori, Rossana; Sormani, Maria Pia; Bonini, Chiara; Venturini, Massimo; Politi, Letterio S; Torrente, Yvan; Ciceri, Fabio

    2015-12-01

    Intra-arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first-in-human, exploratory, non-randomized open-label phase I-IIa clinical trial of intra-arterial HLA-matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor-derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2-month intervals, preceded and followed by clinical, laboratory, and muscular MRI analyses. Two months after the last infusion, a muscle biopsy was performed. Safety was the primary endpoint. The study was relatively safe: One patient developed a thalamic stroke with no clinical consequences and whose correlation with mesoangioblast infusion remained unclear. MRI documented the progression of the disease in 4/5 patients. Functional measures were transiently stabilized in 2/3 ambulant patients, but no functional improvements were observed. Low level of donor DNA was detected in muscle biopsies of 4/5 patients and donor-derived dystrophin in 1. Intra-arterial transplantation of donor mesoangioblasts in human proved to be feasible and relatively safe. Future implementation of the protocol, together with a younger age of patients, will be needed to approach efficacy. PMID:26543057

  1. Buckling instability in arteries.

    PubMed

    Vandiver, Rebecca M

    2015-04-21

    Arteries can become tortuous in response to abnormal growth stimuli, genetic defects and aging. It is suggested that a buckling instability is a mechanism that might lead to artery tortuosity. Here, the buckling instability in arteries is studied by examining asymmetric modes of bifurcation of two-layer cylindrical structures that are residually stressed. These structures are loaded by an axial force, internal pressure and have nonlinear, anisotropic, hyperelastic responses to stresses. Strain-softening and reduced opening angle are shown to lower the critical internal pressure leading to buckling. In addition, the ratio of the media thickness to the adventitia thickness is shown to have a dramatic impact on arterial instability.

  2. The middle suprarenal artery arising from the superior mesenteric artery.

    PubMed

    Honma, Satoru; Kudo, Motoi

    2012-01-01

    We observed a rare case of the middle suprarenal artery branching out from the superior mesenteric artery in a 78-year-old male. This atypical artery enters the right suprarenal gland that was also supplied by the superior and the inferior suprarenal arteries as usual. In embryonic stages, vasculature of the vitelline system and the gonadal system is differentially organized. The superior mesenteric artery has been generally thought to be pure vitelline, since there has been no evidence that the superior mesenteric artery supplies other organs than digestive. We then speculate that the present middle suprarenal artery is a remnant of the embryonic gonadal artery from the superior mesenteric artery, whereas a stem artery to the testis disappeared. Surgeons should take notice of the middle suprarenal artery when operations are conducted around the superior mesenteric artery.

  3. Balloon-Expandable Stent Placement in Patients with Immediate Reocclusion after Initial Successful Thrombolysis of Acute middle Cerebral Arterial Obstruction

    PubMed Central

    Lee, H.K.; Kwak, H.S.; Chung, G.H.; Hwang, S.B.

    2012-01-01

    Summary We present the results of our approach for treating 12 consecutive cases of acute middle cerebral artery (MCA) stroke by performing balloon-expandable stent (BES) placement after immediate reocclusion due to the underlying stenosis after intra-arterial thrombolysis (IAT). We retrospectively reviewed the clinical outcomes of 12 patients with acute MCA stroke who underwent recanalization by BES placement in an underlying stenosis after IAT. The time to treatment, urokinase dose, duration of the procedure, recanalization rates and symptomatic hemorrhage were analyzed. Clinical outcome measures were assessed on admission and at discharge (the National Institutes of Health stroke scores [NIHSS]) as well as three months after treatment (modified Rankin scales [mRS]). The median NIHSS score on admission was 8.6. Four patients received IV rtPA. The median time from symptom onset to IAT was 236 minutes and the median duration of IAT was 62 minutes. The median dose of urokinase was 140,000 units. Initial recanalization after stent deployment (thrombolysis in cerebral ischemia attack grade of II or III) was achieved in all patients. Two patients died in the hospital due to aspiration pneumonia during medical management. In two patients, in-stent reocclusion occurred within 48 hours after stent deployment. At discharge, the median NIHSS score in ten patients (including the patients with reobstruction) was 2.4. The three-month outcome was excellent (mRS, 0-1) in eight patients. In this study, BES deployment was safe and effective in patients with an immediately reoccluded MCA after successful IAT. PMID:22440605

  4. Temporal effects of infused corticosterone and aldosterone on plasma glucose levels in the American bullfrog (Rana catesbeiana).

    PubMed

    Broughton, R E; deRoos, R

    1984-02-01

    The effects of a single infusion of corticosterone or aldosterone on plasma glucose levels were compared in the American bullfrog (Rana catesbeiana). The corticoids were administered, and serial blood samples were collected, via a cannula placed in the common iliac artery. Plasma glucose was estimated by the glucose oxidase method. Plasma glucose levels were essentially unchanged from the time-zero levels at 3 hr after the infusion of 1.0 mg/100 g body wt of corticosterone. The levels subsequently increased to maxima that were approximately 45% greater than the time-zero levels at 9 through 24 hr and then declined to approximately the initial levels by 48 hr after treatment. Infusion of 0.24 mg/100 g body wt of aldosterone did not significantly alter plasma glucose levels. The results suggest that elevated circulating corticosterone is not involved in the primary hyperglycemic response to a stress, but may function synergistically and sequentially with elevated circulating catecholamines in subsequent compensatory adjustments.

  5. Infusing Social Responsibility into the Curriculum and Cocurriculum: Campus Examples

    ERIC Educational Resources Information Center

    Reason, Robert D.

    2013-01-01

    This chapter highlights good practices and lessons learned for infusing social responsibility--contributing to the larger community and taking seriously the perspectives of others--as outcomes of college.

  6. Metabolic and antioxidant profiles of herbal infusions and decoctions.

    PubMed

    Fotakis, Charalambos; Tsigrimani, Diamantina; Tsiaka, Thalia; Lantzouraki, Dimitra Z; Strati, Irini F; Makris, Constantinos; Tagkouli, Dimitra; Proestos, Charalampos; Sinanoglou, Vassilia J; Zoumpoulakis, Panagiotis

    2016-11-15

    This study implements NMR metabolomics and spectrophotometric studies (Folin-Ciocalteu, FRAP, ABTS) to infusions and decoctions of ten plant species in order to assess and compare the metabolic and antioxidant profiles for each botanical family. Multivariate and univariate data analyses highlighted the differences among the samples and pinpointed specific classes of compounds for each plant species as well as infusions and decoctions. The identified phenolic compounds by NMR, as well as the antioxidant profile, framed a trend of increased values in infusions compared to the decoctions. Moreover, the infusion procedure positively affected the extractability of the phenolic compounds compared to decoctions. The highest total phenolic content was found in Mentha spicata, while the lowest in Matricaria chamomilla preparations, irrespective of the preparation method. The preparation time for the decoctions was examined showing that the 15min preparations were generally found richer in phenolics and of higher antioxidant capacity. PMID:27283718

  7. The Infusion of Multicultural Teaching in the Classroom.

    ERIC Educational Resources Information Center

    Yao, Esther Lee

    1984-01-01

    Multicultural education can be infused into the existing curriculum to help students become less ethnocentric and more cosmopolitan. Multicultural lessons dealing with numerals, abacus, calendars, and money exchange that were implemented successfully into a mathematics unit are discussed. (DF)

  8. Antioxidant and astroprotective effects of a Pulicaria incisa infusion.

    PubMed

    Elmann, Anat; Telerman, Alona; Mordechay, Sharon; Erlank, Hilla; Ofir, Rivka

    2012-01-01

    Oxidative stress is involved in the pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Astrocytes, the most abundant glial cells in the brain, protect neurons from reactive oxygen species (ROS) and provide them with trophic support, such as glial-derived neurotrophic factor (GDNF). Thus, any damage to astrocytes will affect neuronal survival. In the present study, an infusion prepared from the desert plant Pulicaria incisa (Pi) was tested for its protective and antioxidant effects on astrocytes subjected to oxidative stress. The Pi infusion attenuated the intracellular accumulation of ROS following treatment with hydrogen peroxide and zinc and prevented the H(2)O(2)-induced death of astrocytes. The Pi infusion also exhibited an antioxidant effect in vitro and induced GDNF transcription in astrocytes. It is proposed that this Pi infusion be further evaluated for use as a functional beverage for the prevention and/or treatment of brain injuries and neurodegenerative diseases in which oxidative stress plays a role.

  9. Infusing Personal Responsibility into the Curriculum and Cocurriculum: Campus Examples

    ERIC Educational Resources Information Center

    O'Neill, Nancy

    2013-01-01

    This chapter highlights good practices and lessons learned for infusing personal responsibility--striving for excellence, cultivating academic integrity, and developing competence in ethical and moral reasoning and action--as outcomes of college.

  10. Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP.

    PubMed

    Mortensen, S P; Mørkeberg, J; Thaning, P; Hellsten, Y; Saltin, B

    2012-05-15

    During exercise, contracting muscles can override sympathetic vasoconstrictor activity (functional sympatholysis). ATP and adenosine have been proposed to play a role in skeletal muscle blood flow regulation. However, little is known about the role of muscle training status on functional sympatholysis and ATP- and adenosine-induced vasodilation. Eight male subjects (22 ± 2 yr, Vo(2max): 49 ± 2 ml O(2)·min(-1)·kg(-1)) were studied before and after 5 wk of one-legged knee-extensor training (3-4 times/wk) and 2 wk of immobilization of the other leg. Leg hemodynamics were measured at rest, during exercise (24 ± 4 watts), and during arterial ATP (0.94 ± 0.03 μmol/min) and adenosine (5.61 ± 0.03 μmol/min) infusion with and without coinfusion of tyramine (11.11 μmol/min). During exercise, leg blood flow (LBF) was lower in the trained leg (2.5 ± 0.1 l/min) compared with the control leg (2.6 ± 0.2 l/min; P < 0.05), and it was higher in the immobilized leg (2.9 ± 0.2 l/min; P < 0.05). Tyramine infusion lowers LBF similarly at rest, but, when tyramine was infused during exercise, LBF was blunted in the immobilized leg (2.5 ± 0.2 l/min; P < 0.05), whereas it was unchanged in the control and trained leg. Mean arterial pressure was lower during exercise with the trained leg compared with the immobilized leg (P < 0.05), and leg vascular conductance was similar. During ATP infusion, the LBF response was higher after immobilization (3.9 ± 0.3 and 4.5 ± 0.6 l/min in the control and immobilized leg, respectively; P < 0.05), whereas it did not change after training. When tyramine was coinfused with ATP, LBF was reduced in the immobilized leg (P < 0.05) but remained similar in the control and trained leg. Training increased skeletal muscle P2Y2 receptor content (P < 0.05), whereas it did not change with immobilization. These results suggest that muscle inactivity impairs functional sympatholysis and that the magnitude of hyperemia and blood pressure response to exercise

  11. Abomasal protein infusions for growing steers fed corn grain rations.

    PubMed

    Johnson, A B; Owens, F N; Mizwicki, K L

    1982-01-01

    Casein was abomasally infused into five growing 226-kg steers consuming a urea-supplemented corn grain diet ad libitum. Infusate solutions in the 5 x 5 Latin square arrangement of treatments contained 0, 20, 40, 80 and 120 g casein made isocaloric and isonitrogenous by the addition of dextrose and urea. Feed intake averaged 5.4 kg dry matter daily and was not altered significantly by abomasal infusions. Apparent digestibility of N decreased from 71.7 to 66.8% as level of casein infusion increased. N retentions (NR) were 40.5, 35.5, 42.8, 35.1 and 32.7 g/d at the five levels of infusion, respectively. A second study was conducted to determine whether level of feed intake influenced the benefit seen from postruminal protein supplementation. Four steers (306 kg) ate ad libitum or were limit-fed (2.5 kg/d) a 1% urea-supplemented corn grain diet in a 4 x 4 Latin square design. These steers were abomasally infused with 120 g casein or an isocaloric, isonitrogenous dextrose-urea mixture. Daily ad libitum feed intake averaged 4.7 kg and was not altered significantly by infusion composition. NR tended to increase with casein infusion at both levels of intake, but, as a percentage, the increase tended to be greater with limit feeding (43 vs 20%). To determine whether supplemental abomasal urea might be beneficial, a third trial was conducted with four 313 kg steers consuming the same diet ad libitum in a crossover design. Infusates consisted of 120 g dextrose or 120 g dextrose plus 42.6 g urea/d. Daily feed intakes were 4.5 and 4.8 kg/d for the steers given the dextrose and the dextrose plus urea infusions, respectively. NR tended to increase with urea infusion (20.9 vs 29.7 g/d). Results suggest that energy, total N or other nutrients, but not postruminal amino acids, limited N balance of young growing steers fed a urea-supplemented, cracked corn diet and gaining weight at .9 kg daily.

  12. Infusing Software Engineering Technology into Practice at NASA

    NASA Technical Reports Server (NTRS)

    Pressburger, Thomas; Feather, Martin S.; Hinchey, Michael; Markosia, Lawrence

    2006-01-01

    We present an ongoing effort of the NASA Software Engineering Initiative to encourage the use of advanced software engineering technology on NASA projects. Technology infusion is in general a difficult process yet this effort seems to have found a modest approach that is successful for some types of technologies. We outline the process and describe the experience of the technology infusions that occurred over a two year period. We also present some lessons from the experiences.

  13. [Radiotherapy and implantable medical device: example of infusion pumps].

    PubMed

    Abrous-Anane, S; Benhassine, S; Lopez, S; Cristina, K; Mazeron, J-J

    2013-12-01

    Indication for radiotherapy is often questioned for patients equipped with implantable medical devices like infusion pumps as the radiation tolerance is poor or not known. We report here on the case of a patient who we treated with pelvic radiotherapy for cervical cancer and who had an infusion pump in iliac fossa. We conducted a series of tests on five identical pumps that insured that the treatment protocol is harmless to the implanted device.

  14. Measuring How Elastic Arteries Function.

    ERIC Educational Resources Information Center

    DeMont, M. Edwin; MacGillivray, Patrick S.; Davison, Ian G.; McConnell, Colin J.

    1997-01-01

    Describes a procedure used to measure force and pressure in elastic arteries. Discusses the physics of the procedure and recommends the use of bovine arteries. Explains the preparation of the arteries for the procedure. (DDR)

  15. Screening for Carotid Artery Stenosis

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of screening for carotid artery stenosis: Health professionals ... blood flow through the arteries. Potential Benefits and Harms of Carotid Artery Stenosis Screening and Treatment The ...

  16. Opioid induced hyperalgesia altered with propofol infusion.

    PubMed

    Kaye, Alan D; Chung, Keun Sam; Vadivelu, Nalini; Cantemir, Catalin; Urman, Richard D; Manchikanti, Laxmaiah

    2014-01-01

    Propofol is a common induction agent that is utilized worldwide in the field of anesthesiology. In recent years, its potential therapeutic role in a variety of patient states has been demonstrated. Controversy exists regarding Propofol mediated analgesic and antihyperalgesic properties. Recent studies have suggested a variety of different mechanisms of action, including modulation of N-Methyl-D- Aspartate receptors and the endocannabinoid system. The N-Methyl-D- Aspartate receptor is part of a larger family of glutamate receptors and is an important mediator of excitatory neurotransmission. In the case presented, the pain experienced by the patient was not well-controlled, in spite of increasing doses of opioids, potentially due to superimposed opioid induced hyperalgesia. In the present case, we demonstrate a cycle of opioid induced hyperalgesia which was successfully affected with a Propofol infusion. Controversial reports exist in animal studies on the analgesic properties of Propofol. Randomized controlled studies in animal models studying the effect of Propofol on pain sensation have shown that Propofol possesses an analgesic effect. This clinical case demonstrates that Propofol could possibly have antihyperalgesic effects on opioid induced hyperalgesia caused by high-doses of chronic opioids and worsened by fentanyl. We postulate that a probable mechanism of complete pain relief after the procedure could be the inhibition of activity of the N-Methyl-D- Aspartate receptor by Propofol because it was the only agent the patient received during the procedure, causing a break of the cycle of opioid induced hyperalgesia. Additional research is required to clarify Propofol mediated or modulated analgesic properties in humans.

  17. Herbal infusions used for induced abortion.

    PubMed

    Ciganda, Carmen; Laborde, Amalia

    2003-01-01

    Plants and herbs have been used to induce abortions but there is very little published information describing the commonly used ones. The purpose of this report is to describe the herbal products used to induce abortions, and to enhance awareness and understanding of their toxic effects. A descriptive retrospective survey was conducted on the calls received by the Montevideo Poison Centre between 1986 and 1999 concerning the ingestion of herbal infusions with abortive intent. A total of 86 cases involving 30 different plant species were identified. The species most frequently involved were ruda (Ruta chalepensis/graveolens), cola de quirquincho (Lycopodium saururus), parsley (Petroselinum hortense), and an over-the-counter herbal product named Carachipita. The components of Carachipita are pennyroyal (Mentha pulegium), yerba de la perdiz (Margiricarpus pinnatus), oregano (Origanum vulgare), and guaycuri (Statice brasiliensis). Abortion occurred in 23 cases after the ingestion of parsley, ruda, Carachipita, celery, Cedron, francisco alvarez, floripon, espina colorada. Out of the 23 cases, 15 involved the only the ingestion of plants, 4 cases used injected drugs (presumably hormones), and in 4 cases there was associated self-inflicted instrumental manipulation. Multiple organ system failure occurred in those patients who had ingested ruda (alone or in combination with parsley or fennel), Carachipita, arnica, or bardana. Deaths occurred in one case of Carachipita ingestion and in 4 cases of ruda ingestion (2 cases of ruda alone, 2 cases of ruda with parsley and fennel). Self-inflicted instrumental manipulations were found in 4 of the patients with multiple organ system failure and in one of those who died. The results of this report are not conclusive, but it appears that the ingestion of plants to induce abortion involves the risk of severe morbidity and mortality.

  18. Urokinase Plasminogen Receptor and the Fibrinolytic Complex Play a Role in Nerve Repair after Nerve Crush in Mice, and in Human Neuropathies

    PubMed Central

    Rivellini, Cristina; Dina, Giorgia; Porrello, Emanuela; Cerri, Federica; Scarlato, Marina; Domi, Teuta; Ungaro, Daniela; Carro, Ubaldo Del; Bolino, Alessandra; Quattrini, Angelo; Comi, Giancarlo; Previtali, Stefano C.

    2012-01-01

    Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies. PMID:22363796

  19. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    SciTech Connect

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P. . E-mail: fpchou@csmu.edu.tw

    2006-07-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-{kappa}B, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.

  20. Fat emulsion infusion potentiates coagulation activation during human endotoxemia.

    PubMed

    van der Poll, T; Coyle, S M; Levi, M; Boermeester, M A; Braxton, C C; Jansen, P M; Hack, C E; Lowry, S F

    1996-01-01

    Intravenous fat emulsions are frequently given to malnourished patients who are prone to suffer from infectious complications. As injection of low dose endotoxin represents a model to study the human response to acute infection, we sought to determine the effect of lipid emulsion infusion on endotoxin-induced activation of the hemostatic mechanism in man. Ten healthy men received a bolus intravenous injection of endotoxin (lot EC-5; 20 U/kg) midway through a 4-h infusion (125 ml/h) of either dextrose 5% (n = 5) or Intralipid 20% (n = 5). Lipid infusion potentiated endotoxin-induced coagulation activation, as indicated by higher plasma levels of the prothrombin fragment F1 + 2 and of thrombin-antithrombin III complexes (both p < 0.05 for the difference between groups). However, lipid infusion did not influence the fibrinolytic response to intravenous endotoxin, as reflected by similar increases in the levels of tissue-type plasminogen activator and plasmin-alpha 2-antiplasmin complexes in both groups. Endotoxin-induced appearance of plasminogen activator inhibitor type I was enhanced by lipid infusion (p < 0.05). These data suggest that fat emulsion infusion may enhance the tendency towards thrombotic complications in patients with infections.

  1. Female Patients Require a Higher Propofol Infusion Rate for Sedation.

    PubMed

    Maeda, Shigeru; Tomoyasu, Yumiko; Higuchi, Hitoshi; Honda, Yuka; Ishii-Maruhama, Minako; Miyawaki, Takuya

    2016-01-01

    Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant-related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery. PMID:27269663

  2. Drop impact dynamics on liquid-infused superhydrophobic surfaces

    NASA Astrophysics Data System (ADS)

    Kim, Jeong-Hyun; Rothstein, Jonathan

    2015-11-01

    In this talk, we present a series of experiments investigating the drop impact dynamics on hydrophobic, air-infused and lubricant-infused superhydrophobic surfaces. To create the superhydrophobic surfaces, smooth Teflon (PTFE) surfaces were roughened by a 240-grit sandpaper. The immiscible and incompressible silicone oils with different viscosities were infused into features of the superhydrophobic surfaces by a skim coating technique. The spreading and retraction dynamics on a series of the tested surfaces will be presented. We will show that the maximal deformation of the drops on lubricant-infused surfaces grows with increasing viscosity ratio between a water drop and the infused oil. We will show that this increase in the maximal deformation with the viscosity ratio is consistent with increasing the velocity and the viscosity of the drops but the rims of the drops destabilize with increasing the drop velocity. Finally, we will demonstrate that increasing the viscosity of the infused oil induces higher viscous force at the contact line, resulting in reduction in the movement of the drops during retraction and corresponding increase in the final drop size.

  3. Electro-osmotic infusion for joule heating soil remediation techniques

    DOEpatents

    Carrigan, Charles R.; Nitao, John J.

    1999-01-01

    Electro-osmotic infusion of ground water or chemically tailored electrolyte is used to enhance, maintain, or recondition electrical conductivity for the joule heating remediation technique. Induced flows can be used to infuse electrolyte with enhanced ionic conductivity into the vicinity of the electrodes, maintain the local saturation of near-electrode regions and resaturate a partially dried out zone with groundwater. Electro-osmotic infusion can also tailor the conductivity throughout the target layer by infusing chemically modified and/or heated electrolyte to improve conductivity contrast of the interior. Periodic polarity reversals will prevent large pH changes at the electrodes. Electro-osmotic infusion can be used to condition the electrical conductivity of the soil, particularly low permeability soil, before and during the heating operation. Electro-osmotic infusion is carried out by locating one or more electrodes adjacent the heating electrodes and applying a dc potential between two or more electrodes. Depending on the polarities of the electrodes, the induced flow will be toward the heating electrodes or away from the heating electrodes. In addition, electrodes carrying a dc potential may be located throughout the target area to tailor the conductivity of the target area.

  4. Female Patients Require a Higher Propofol Infusion Rate for Sedation.

    PubMed

    Maeda, Shigeru; Tomoyasu, Yumiko; Higuchi, Hitoshi; Honda, Yuka; Ishii-Maruhama, Minako; Miyawaki, Takuya

    2016-01-01

    Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant-related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery.

  5. Oxygen-related chemoreceptor drive to breathe during H₂S infusion.

    PubMed

    Haouzi, Philippe; Sonobe, Takashi; Chenuel, Bruno

    2014-09-15

    This study addresses the following question: Could the acute depression in breathing produced by hyperoxia, a reflection of the tonic drive to breathe from the arterial chemoreceptors, be accounted for by a background level of endogenous H2S? To address this question, we produced a stable but moderate increase in breathing (24±11%) via continuous infusion of low levels of H2S, in 10 spontaneously breathing urethane-sedated rats. We found that acute exposure to 100% O2 (20 tests) decreased minute ventilation (V˙(I)) from 301±51 to 210±43 ml/min within 15s in control conditions, but no additional significant drop in V˙(I) was observed during H2S induced hyperpnea. In addition, no decrease in the estimated concentrations of gaseous H2S in the arterial blood was observed during the hyperoxic tests. It is concluded that the ventilatory depression induced by high O2 appears to be limited to the tonic background peripheral chemosensory drive to breathe, but has little or no impact on the CB stimulation produced by low levels of H2S.

  6. The effect of low-dose oxytocin infusion on cerebral hemodynamics in pregnant women.

    PubMed

    van Veen, Teelkien R; Belfort, Michael A; Zeeman, Gerda G

    2011-08-01

    We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive, nonsmoking patients undergoing induction of labor. No vasoactive drugs were used before or during the study period. Measurements were made at baseline and 15, 30, 60, and 120 minutes after oxytocin initiation. Mean arterial pressure, cerebral perfusion pressure, resistance index, resistance area product, and cerebral flow index at different times were calculated and compared using one-way analysis of variance (ANOVA) for repeated measures or Friedman repeated-measures ANOVA as appropriate, with P<0.05 regarded as significant. No significant systemic or cerebrovascular changes were noted after oxytocin initiation, and there was no correlation between the dosage administered and any hemodynamic parameter. Induction-dose oxytocin does not significantly affect selected cerebral hemodynamic parameters in the first 2 hours after initiation.

  7. Oxygen related chemoreceptor drive to breathe during H2S infusion

    PubMed Central

    Philippe, Haouzi; Sonobe, Takashi; Chenuel, Bruno

    2014-01-01

    This study addresses the following question: Could the acute depression in breathing produced by hyperoxia, a reflection of the tonic drive to breathe from the arterial chemoreceptors, be accounted for by the presence a background level of local endogenous H2S? To address this question, we produced a stable but moderate increase in breathing (24 ± 11%) via continuous infusion of low levels of H2S, in 10 spontaneously breathing urethane-sedated rats. We found that acute exposure to 100% O2 (20 tests) decreased minute ventilation (VI) from 301 ± 51 to 210 ± 43 ml/min within 15 seconds in control conditions, but no additional significant drop in VI was observed during H2S induced hyperpnea. In addition, no decrease in the estimated concentrations of gaseous H2S in the arterial blood was observed during the hyperoxic tests. It is concluded that the ventilatory depression induced by high O2 appears to be limited to the tonic background peripheral chemosensory drive to breathe, but has little or no impact on the CB stimulation produced by low levels of H2S. PMID:24973475

  8. Diagnosis of Intracranial Artery Dissection

    PubMed Central

    KANOTO, Masafumi; HOSOYA, Takaaki

    2016-01-01

    Cerebral arterial dissection is defined as a hematoma in the wall of a cervical or an intracranial artery. Cerebral arterial dissection causes arterial stenosis, occlusion, and aneurysm, resulting in acute infarction and hemorrhage. Image analysis by such methods as conventional angiography, computed tomography, magnetic resonance imaging, and so on plays an important role in diagnosing cerebral arterial dissection. In this study, we explore the methods and findings involved in the diagnosis of cerebral arterial dissection. PMID:27180630

  9. Coronary artery stent (image)

    MedlinePlus

    ... with a balloon catheter and expands when the balloon is inflated. The stent is then left there to help keep the artery open. ... with a balloon catheter and expands when the balloon is inflated. The stent is then left there to help keep the artery open.

  10. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  11. Coronary artery disease (image)

    MedlinePlus

    ... through these arteries is critical for the heart. Coronary artery disease usually results from the build-up of fatty material and plaque, a condition called atherosclerosis. As the ... blood to the heart can slow or stop, causing chest pain (stable ...

  12. Duration of eptifibatide infusion after percutaneous coronary intervention and outcomes among high-risk patients with non-ST-segment elevation acute coronary syndrome: insights from EARLY ACS

    PubMed Central

    Hess, Connie N; Schulte, Phillip J; Steg, Philippe Gabriel; Dalby, Anthony J; Schweiger, Marc J; Lewis, Basil S; Armstrong, Paul W; Califf, Robert M; van de Werf, Frans; Harrington, Robert A

    2013-01-01

    Background and Objectives: Eptifibatide is indicated during percutaneous coronary intervention (PCI) with continuation for 18–24 hours post procedure but is associated with bleeding. We examined the efficacy and safety of shorter post-PCI eptifibatide infusions in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients. Methods: EARLY ACS patients treated with PCI and eptifibatide were grouped by post-procedure infusion duration: <10, 10–13, 13–17, and 17–25 (per protocol) hours. Adjusted estimated event rates for 96-hour death/myocardial infarction (MI)/recurrent ischaemia requiring urgent revascularization (RIUR), 30-day death/MI, post-PCI packed red blood cell (PRBC) transfusion, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate/severe bleeding were obtained using inverse-propensity weighting to account for informative censoring of infusions. Results: Among 3271 eptifibatide-treated PCI patients, there were 66 96-hour death/MI/RIUR events, 94 30-day death/MI events, 127 PRBC transfusions, and 115 GUSTO moderate/severe bleeds. Compared with per protocol, patients receiving post-PCI infusions <10 hours had similar adjusted estimated rates of 96-hour death/MI/RIUR (absolute difference 0.021 higher; 0.040 vs. 0.019, 95% CI −0.023 to 0.064; p=0.35) and 30-day death/MI (0.020 higher; 0.046 vs. 0.026, 95% CI −0.021 to 0.062; p=0.34). There were also no differences in ischaemic outcomes between infusions of 10–17 hours and per-protocol infusions. Adjusted estimated rates of PRBC transfusion were higher for the <10-hour infusion group compared with per protocol (0.048 higher; 0.079 vs. 0.031, 95% CI 0.005 to 0.091, p=0.03) but were similar for other groups. Adjusted GUSTO moderate/severe bleeding rates were similar to per-protocol rates for all groups. Conclusions: In high-risk NSTE ACS patients, post-PCI eptifibatide infusions <18 hours were not associated with

  13. Volatile fraction of lavender and bitter fennel infusion extracts.

    PubMed

    Tschiggerl, Christine; Bucar, Franz

    2010-09-01

    The relative proportions of chemical classes (hydrocarbons, oxides, alcohols/ethers, aldehydes/ketones, acids/esters/lactones) in the essential oil of lavender (Lavendula angustifolia Mill., family Lamiaceae) and bitter fennel (Foeniculum vulgare Mill. subsp. vulgare var. vulgare (Mill.) Thellung, family Apiaceae) and in the volatile fraction of infusion extracts were examined and showed remarkable differences. The volatile compounds of infusions were isolated by hydrodistillation and solid phase extraction (SPE). Their qualitative and semiquantitative compositions were compared with the essential oil isolated by hydrodistillation directly from the plant material and analyzed by GC-MS. Furthermore, quantification of the major constituents of lavender oil and of the volatile fraction obtained by hydrodistillation of the infusion was performed. Comparison of the total essential oil yield quantified by hydrodistillation of the lavender infusion (0.7% v/w, corresponding to plant material) with the essential oil yield of the blossoms (5.1% v/w) revealed that only 13.9% of the initial oil could be extracted by infusion. The main constituents of the volatile fraction of the lavender infusion were (hydrodistillation/SPE): linalool (39.3%/28.2%), 1,8 cineole (24.8%/18.9%), cis-linalool oxide (furanoid) (5.8%/8.0%), trans-linalool oxide (furanoid) (4.1%/7.1%), camphor (5.3%/4.0%) and alpha-terpineol (4.0%/3.0%). The major constituents of lavender essential oil were linalool (28.8%), 1,8-cineole (18.05%), linalyl acetate (13.9%) and alpha-terpineol (4.0%). Most intriguing, in the volatile fraction of lavender infusion a significant proportional decrease of linalyl acetate and an increase of linalool oxides was recognized. The essential oil yield of fennel fruits was 12.5% v/w, whereas 1.8% v/w volatile fraction (corresponding to plant material) was obtained by hydrodistillation of the fennel infusion, which is equivalent to 14.5% of the initial fennel essential oil. The main

  14. Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology

    PubMed Central

    Tseliou, Eleni; Kanazawa, Hideaki; Dawkins, James; Gallet, Romain; Kreke, Michelle; Smith, Rachel; Middleton, Ryan; Valle, Jackelyn; Marbán, Linda; Kar, Saibal; Makkar, Rajendra; Marbán, Eduardo

    2016-01-01

    Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients. PMID:26784932

  15. Pharmacokinetic analysis of coronary venous retroinfusion: a comparison with anterograde coronary artery drug administration using metoprolol as a tracer.

    PubMed

    Rydén, L; Tadokoro, H; Sjöquist, P O; Regardh, C; Kobayashi, S; Corday, E; Drury, J K

    1991-08-01

    Plasma and myocardial tissue concentrations of metoprolol were studied in ischemic and nonischemic areas of 22 pigs after 90 (n = 19) and 16 (n = 3) min of left anterior descending coronary artery occlusion. Group A (n = 6) received simultaneous intravenous metoprolol (0.2 mg/kg body weight) and tritium-labeled (3H)-metoprolol (0.2 mg/kg) retrogradely into the coronary vein. In group B (n = 5), metoprolol and 3H-metoprolol were administered in the same way, but at half the volume to study the influence of derived coronary venous pressure on the myocardial concentration of drug. In group C (n = 3), metoprolol was given retrogradely and saline solution was infused into the left anterior descending artery before induced death to wash out metoprolol from the coronary veins. To rule out a possible influence of the development of myocardial necrosis on drug distribution, metoprolol was retroinfused after 1 min of arterial occlusion in three pigs (group D). In group E (n = 5), metoprolol (0.2 mg/kg) was infused anterogradely into the left anterior descending artery. Peak plasma concentration was significantly higher after intravenous infusion of metoprolol (1,188 +/- 503 nmol/liter) than after coronary venous infusion (417 +/- 155 nmol/liter; p less than 0.001). In groups A and B, the nonischemic myocardial concentration of metoprolol was 250 to 300 pmol/g, whether the drug was infused intravenously or into the coronary vein. Coronary venous retroinfusion, however, resulted in a substantial accumulation of metoprolol in the ischemic myocardium. In group A pigs, subendocardial myocardial concentration was 16,800 +/- 7,774, mid-myocardial 39,590 +/- 18,043 and subepicardial 57,143 +/- 29,030 pmol/g (mean +/- SE). The ischemic myocardial concentration in pigs from group B was somewhat less pronounced, probably secondary to a lower coronary venous pressure (15 +/- 3 mm Hg) with the lower volume of infusion (6.1 +/- 0.3 ml) in group B compared with 32 +/- 5 mm Hg with a 14

  16. [Treatment outcome of chemotherapy with superselective cerebral artery catheterization in vegetative state patients].

    PubMed

    Kondrat'eva, E A; Panuntsev, V S; Pak, V A; Chachkhaliia, M Kh; Tsentsiper, L M; Kondrat'ev, S A; Borovikova, V N

    2011-01-01

    The purpose of the study is to assess the impact of superselective neurotransmitter metabolic therapy in patients in a vegetative state. Superselective intraarterial infusion was conducted on 26 patients with relevant international criteria for the diagnosis of vegetative state. Comprehensive assessment of neurologic symptoms and severity of low metabolism on PET scan allowed to select the vascular pool, for the catheter installation. The catheter was placed either in the carotid or the vertebrobasilar pool. Infusion of neurotransmitter agents was conducted for 7 days continuously. Control of the level of metabolism of labeled glucose in the brain (PET) was performed within 2 weeks after arterial infusion. 14 out of 26 patients showed a positive trend of changes in energy metabolism of the brain. However, only 7 out of 14 patients showed further recovery of consciousness. The data confirms that the delivery path and a combination of medications play a definite role in the effectiveness of vegetative state therapy. PMID:21692220

  17. Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer.

    PubMed Central

    Yamashita, J.; Ogawa, M.; Yamashita, S.; Nakashima, Y.; Saishoji, T.; Nomura, K.; Inada, K.; Kawano, I.

    1993-01-01

    Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were

  18. Epitope-mapped monoclonal antibodies as tools for functional and morphological analyses of the human urokinase receptor in tumor tissue.

    PubMed Central

    Luther, T.; Magdolen, V.; Albrecht, S.; Kasper, M.; Riemer, C.; Kessler, H.; Graeff, H.; Müller, M.; Schmitt, M.

    1997-01-01

    uPAR (CD87), the receptor for the urokinase-type plasminogen activator (uPA) facilitates tumor cell invasion and metastasis by focusing uPA proteolytic activity to the cell surface. As uPAR exists in various molecular forms, it is desirable to use well defined antibodies for analyses of uPAR antigen expression in human malignant tumors by immunological methods. Therefore, twelve monoclonal antibodies (MAbs) directed against uPAR were generated by using nonglycosylated, recombinant human uPAR (spanning amino acids 1 to 284), expressed in Escherichia coli, as the immunogen. The reaction pattern of these MAbs with the immunogen and a series of carboxyl-terminally truncated versions of uPAR demonstrated that at least six different epitopes of uPAR are recognized. All MAbs reacted under reducing conditions in immunoblot analyses with E. coli-expressed uPA and also with highly glycosylated, functionally intact, recombinant human uPAR expressed in Chinese hamster ovary (CHO) cells. Seven of the MAbs recognized CHO uPAR under nonreducing conditions as well. By flow cytofluorometric analyses, three of these MAbs were shown to bind to native human uPAR present on the cell surface of monocytoid U937 cells with MAb IIIF10 being the best. Saturation of uPAR with uPA on U937 cells completely blocked interaction of MAb IIIF10 with uPAR (mapped epitope, amino acids 52 to 60 of domain I of uPAR). In turn, preincubation of U937 cells with MAb IIIF10 efficiently reduced binding of uPA to uPAR, indicating that the epitope detected by MAb IIIF10 is located within or closely to the uPA-binding site of uPAR, and thus, this site may be a target to influence uPA/uPAR-mediated proteolysis in tumors. Binding of MAbs IID7 or IIIB11 (mapped epitope, amino acids 125 to 132 of domain II of uPAR) to uPAR is not affected when uPAR is occupied by uPA. As these MAbs reacted strongly with cellular uPAR antigen in formalin-fixed paraffin-embedded tumor sections, the domain-II-specific antibodies IID7

  19. Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema.

    PubMed

    Hilty, Matthias Peter; Zügel, Stefanie; Schoeb, Michele; Auinger, Katja; Dehnert, Christoph; Maggiorini, Marco

    2016-01-01

    Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9 ± 0.4 at SL versus 2.3 ± 0.5 at HA, p < 0.01), CRP (0.7 ± 0.5 at SL versus 3.6 ± 4.6 at HA, p < 0.01), and IL-6 (0.8 ± 0.4 at SL versus 3.3 ± 4.9 at HA, p < 0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r = 0.46, p < 0.001), but not suPAR (r = 0.27, p = 0.08); the increase in IL-6 was not correlated with suPAR (r = 0.16, p = 0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0 ± 0.4 versus 1.8 ± 0.4, p = 0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict

  20. Structural analysis and tissue localization of human C4.4A: a protein homologue of the urokinase receptor.

    PubMed Central

    Hansen, Line V; Gårdsvoll, Henrik; Nielsen, Boye S; Lund, Leif R; Danø, Keld; Jensen, Ole N; Ploug, Michael

    2004-01-01

    C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor (uPAR), was originally identified as a metastasis-associated membrane protein, but little is known about its structural and functional properties. Therefore, we expressed, purified and characterized a soluble truncated form of human C4.4A, and used this protein to produce specific polyclonal anti-C4.4A antibodies. By immunohistochemistry we observed a pronounced surface staining for C4.4A in suprabasal keratinocytes of chronic human wounds and found C4.4A expression markedly upregulated in migrating keratinocytes during re-epithelisation of incisional skin wounds. Phorbol-ester-induced hyperplasia of mouse skin is also accompanied by a significant induction of C4.4A expression in the multilayered, suprabasal keratinocytes. C4.4A contains two Ly-6 (leucocyte antigen 6)/uPAR/alpha-neurotoxin modules. Our recombinant human C4.4A is extensively modified by post-translational glycosylation, which include 5-6 N-linked carbohydrates primarily located in or close to its second Ly-6/uPAR/alpha-neurotoxin module and approximately 15 O-linked carbohydrates clustered in a Ser/Thr/Pro-rich region at the C-terminus. A highly protease-sensitive region (Tyr200-Arg204) is located between these two clusters of N- and O-linked carbohydrates. The natural, glycolipid-anchored C4.4A from amnion membranes of human term placenta exhibits similar properties. Using recombinant, soluble C4.4A or MCF 7 cells, which express significant amounts of GPI-anchored C4.4A, we find no evidence for an interaction between C4.4A and uPA, a property suggested previously for rat C4.4A. Collectively these data indicate that C4.4A, although being a structural homologue of uPAR, is unlikely to have a functional overlap with uPAR. PMID:15012588

  1. Expression and functional role of urokinase-type plasminogen activator receptor in normal and acute leukaemic cells.

    PubMed

    Lanza, F; Castoldi, G L; Castagnari, B; Todd, R F; Moretti, S; Spisani, S; Latorraca, A; Focarile, E; Roberti, M G; Traniello, S

    1998-10-01

    Urokinase-type plasminogen activator receptor (UPA-R-CD87) is a GPI-anchored membrane protein which promotes the generation of plasmin on the surface of many cell types, probably facilitating cellular extravasation and tissue invasion. A flow cytometric quantitative analysis of expression levels for UPA-R was performed on fresh blast cells from patients with acute myeloid leukaemia (AML, n = 74), acute lymphoblastic leukaemia (ALL, n = 24), and biphenotypic leukaemia (BAL, n = 3) using two CD87 monoclonal antibodies (McAbs) (3B10 and VIM5). Peripheral blood and bone marrow (BM) cells from 15 healthy adults served as controls. Using 3B10 McAb, UPA-R was expressed (>99%) by blood monocytes, neutrophils, and BM myelomonocytic precursors in controls, whereas resting T and B lymphocytes, and CD34+ cells were UPA-R negative. We also attempted to clarify whether UPA-R has a role in mediating neutrophil functions. Oriented locomotion induced by different chemotaxins and lysozyme release by granules stimulated with fMLP or PMA were significantly decreased when UPA-R was neutralized by CD87 McAb. In contrast, the anti-UPA-R McAb had no effect on superoxide anion generation of normal neutrophils. Blasts from AML showed a heterogenous pattern of expression for the UPA-R McAbs, with reactivity strictly dependent on FAB subtype. The highest UPA-R expression was seen in the M5 group: all patients tested (n = 20) showed strong positivity for the UPA-R McAb whereas only 12% (3/24) of ALL patients were CD87 positive, and 2/3 of BAL patients showed a dim expression for CD87. The number of receptors expressed by blast cells in 6/74 (8.1%) AML patients was higher than those of normal samples: in addition, since co-expression of UPA-R and CD34 was not found in normal haemopoietic cells, it may be postulated that CD87 can be used alone (when overexpressed) or in combination with CD34 for the detection of minimal residual disease. Results also indicated that patients with UPA

  2. Presence of urokinase in serum-free primary rat hepatocyte cultures and its role in activating hepatocyte growth factor.

    PubMed

    Mars, W M; Kim, T H; Stolz, D B; Liu, M L; Michalopoulos, G K

    1996-06-15

    Serum-free rat hepatocyte cultures can be stimulated to divide by the inactive, single-chain form of hepatocyte growth factor (scHGF), suggesting that hepatocytes contain a protein that can cleave scHGF to its biologically active, two-chain (tcHGF) form. We added radiolabeled scHGF to serum-free cultures and confirmed that tcHGF was being generated. Because scHGF can be cleaved to tcHGF by plasminogen activators (PAs), we next tested the cultures for active PA. Although little PA activity was initially present, the majority was of the urokinase type (u-PA) as determined by neutralization studies using either a polyclonal antibody against u-PA or, since u-PA functions in the context of its receptor (u-PAR), a monoclonal antibody against u-PAR. Considerable PA activity developed within 24 h, which was also neutralizable with antibody. To test whether the active, receptor-bound u-PA from the cell cultures was cleaving scHGF, iodinated scHGF was added to intact cells in the presence of the antibody against u-PAR. Comparison to control cultures determined that the antibody prevented scHGF cleavage. Analysis of cultures treated with HGF, epidermal growth factor, and transforming growth factor alpha (TGF-alpha) alpha showed these growth factors increased the hepatocyte PA activity in parallel with the mRNA for u-PA. TGF-beta had the opposite effect, and when TGF-beta was added to the culture system, conversion of scHGF to tcHGF was prevented in concert with the production of the type 1 PA inhibitor. When liver remnants from hepatectomized animals were assayed for active TGF-beta, elevated protein was found just prior to the appearance of PA inhibitor 1 message and protein. Collectively, our data show that in culture, active u-PA is present and cleaves scHGF to tcHGF in the context of its receptor. It also suggests that modulation of u-PA activity by various growth factors is relevant for regulating cleavage of scHGF to tcHGF both in vitro and in vivo.

  3. Soluble Urokinase-Type Plasminogen Activator Receptor Plasma Concentration May Predict Susceptibility to High Altitude Pulmonary Edema

    PubMed Central

    Zügel, Stefanie; Schoeb, Michele; Auinger, Katja; Dehnert, Christoph; Maggiorini, Marco

    2016-01-01

    Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9 ± 0.4 at SL versus 2.3 ± 0.5 at HA, p < 0.01), CRP (0.7 ± 0.5 at SL versus 3.6 ± 4.6 at HA, p < 0.01), and IL-6 (0.8 ± 0.4 at SL versus 3.3 ± 4.9 at HA, p < 0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r = 0.46, p < 0.001), but not suPAR (r = 0.27, p = 0.08); the increase in IL-6 was not correlated with suPAR (r = 0.16, p = 0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0 ± 0.4 versus 1.8 ± 0.4, p = 0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict

  4. Tumour Microenvironments Induce Expression of Urokinase Plasminogen Activator Receptor (uPAR) and Concomitant Activation of Gelatinolytic Enzymes

    PubMed Central

    Magnussen, Synnøve; Hadler-Olsen, Elin; Latysheva, Nadezhda; Pirila, Emma; Steigen, Sonja E.; Hanes, Robert; Salo, Tuula; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjørg

    2014-01-01

    Background The urokinase plasminogen activator receptor (uPAR) is associated with poor prognosis in oral squamous cell carcinoma (OSCC), and increased expression of uPAR is often found at the invasive tumour front. The aim of the current study was to elucidate the role of uPAR in invasion and metastasis of OSCC, and the effects of various tumour microenvironments in these processes. Furthermore, we wanted to study whether the cells’ expression level of uPAR affected the activity of gelatinolytic enzymes. Methods The Plaur gene was both overexpressed and knocked-down in the murine OSCC cell line AT84. Tongue and skin tumours were established in syngeneic mice, and cells were also studied in an ex vivo leiomyoma invasion model. Soluble factors derived from leiomyoma tissue, as well as purified extracellular matrix (ECM) proteins, were assessed for their ability to affect uPAR expression, glycosylation and cleavage. Activity of gelatinolytic enzymes in the tissues were assessed by in situ zymography. Results We found that increased levels of uPAR did not induce tumour invasion or metastasis. However, cells expressing low endogenous levels of uPAR in vitro up-regulated uPAR expression both in tongue, skin and leiomyoma tissue. Various ECM proteins had no effect on uPAR expression, while soluble factors originating from the leiomyoma tissue increased both the expression and glycosylation of uPAR, and possibly also affected the proteolytic processing of uPAR. Tumours with high levels of uPAR, as well as cells invading leiomyoma tissue with up-regulated uPAR expression, all displayed enhanced activity of gelatinolytic enzymes. Conclusions Although high levels of uPAR are not sufficient to induce invasion and metastasis, the activity of gelatinolytic enzymes was increased. Furthermore, several tumour microenvironments have the capacity to induce up-regulation of uPAR expression, and soluble factors in the tumour microenvironment may have an important role in the

  5. Preparation and antitumor effect of a toxin-linked conjugate targeting vascular endothelial growth factor receptor and urokinase plasminogen activator

    PubMed Central

    Xiang, Ying; Li, Qiying; Huang, Dehong; Tang, Xianjun; Wang, Li; Shi, Yang; Zhang, Wenjun; Yang, Tao; Xiao, Chunyan

    2015-01-01

    The aberrant signaling activation of vascular endothelial growth factor receptor (VEGFR) and urokinase plasminogen activator (uPA) is a common characteristic of many tumors, including lung cancer. Accordingly, VEGFR and uPA have emerged as attractive targets for tumor. KDR (Flk-1/VEGFR-2), a member of the VEGFR family, has been recognized as an important target for antiangiogenesis in tumor. In this study, a recombinant immunotoxin was produced to specifically target KDR-expressing tumor vascular endothelial cells and uPA-expressing tumor cells and mediate antitumor angiogenesis and antitumor effect. Based on its potent inhibitory effect on protein synthesis, Luffin-beta (Lβ) ribosome-inactivating protein was selected as part of a recombinant fusion protein, a single-chain variable fragment against KDR (KDRscFv)-uPA cleavage site (uPAcs)-Lβ-KDEL (named as KPLK). The KDRscFv-uPAcs-Lβ-KDEL (KPLK) contained a single-chain variable fragment (scFv) against KDR, uPAcs, Lβ, and the retention signal for endoplasmic reticulum proteins KDEL (Lys-Asp-Glu-Leu). The KPLK-expressing vector was expressed in Escherichia coli, and the KPLK protein was isolated with nickel affinity chromatography and gel filtration chromatography. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis test demonstrated KPLK was effectively expressed. Result of in vitro cell viability assay on non-small cell lung cancer (NSCLC) H460 cell line (uPA-positive cell) revealed that KPLK significantly inhibited cell proliferation, induced apoptosis, and accumulated cells in S and G2/M phases, but the normal cell line (human submandibular gland cell) was unaffected. These effects were enhanced when uPA was added to digest KPLK to release Lβ. For in vivo assay of KPLK, subcutaneous xenograft tumor model of nude mice were established with H460 cells. Growth of solid tumors was significantly inhibited in animals treated with KPLK up to 21 days, tumor weights were decreased, and the expression of

  6. Low-molecular-weight dextran infusion is more effective for the treatment of hemoconcentration due to severe ovarian hyperstimulation syndrome than human albumin infusion.

    PubMed

    Endo, Toshiaki; Kitajima, Yoshimitsu; Hayashi, Takuhiro; Fujii, Miho; Hata, Hiroshi; Azumaguchi, Atsushi

    2004-11-01

    The most severe complication of ovarian hyperstimulation syndrome (OHSS) is thromboembolism, which is related to hemoconcentration. Dextran 40 infusion has greater effectiveness for the treatment of hemoconcentration due to OHSS than does human albumin infusion. PMID:15533378

  7. Planetary Science Technology Infusion Study: Findings and Recommendations Status

    NASA Technical Reports Server (NTRS)

    Anderson, David J.; Sandifer, Carl E., II; Sarver-Verhey, Timothy R.; Vento, Daniel M.; Zakrajsek, June F.

    2014-01-01

    The Planetary Science Division (PSD) within the National Aeronautics and Space Administrations (NASA) Science Mission Directorate (SMD) at NASA Headquarters sought to understand how to better realize a scientific return on spacecraft system technology investments currently being funded. In order to achieve this objective, a team at NASA Glenn Research Center was tasked with surveying the science and mission communities to collect their insight on technology infusion and additionally sought inputs from industry, universities, and other organizations involved with proposing for future PSD missions. This survey was undertaken by issuing a Request for Information (RFI) activity that requested input from the proposing community on present technology infusion efforts. The Technology Infusion Study was initiated in March 2013 with the release of the RFI request. The evaluation team compiled and assessed this input in order to provide PSD with recommendations on how to effectively infuse new spacecraft systems technologies that it develops into future competed missions enabling increased scientific discoveries, lower mission cost, or both. This team is comprised of personnel from the Radioisotope Power Systems (RPS) Program and the In-Space Propulsion Technology (ISPT) Program staff.The RFI survey covered two aspects of technology infusion: 1) General Insight, including: their assessment of barriers to technology infusion as related to infusion approach; technology readiness; information and documentation products; communication; integration considerations; interaction with technology development areas; cost-capped mission areas; risk considerations; system level impacts and implementation; and mission pull. 2) Specific technologies from the most recent PSD Announcements of Opportunities (AOs): The Advanced Stirling Radioisotope Generator (ASRG), aerocapture and aeroshell hardware technologies, the NASA Evolutionary Xenon Thruster (NEXT) ion propulsion system, and the

  8. Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

    PubMed

    Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

    2015-09-01

    Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease

  9. Topotecan Delivery to the Optic Nerve after Ophthalmic Artery Chemosurgery

    PubMed Central

    Taich, Paula; Requejo, Flavio; Asprea, Marcelo; Sgroi, Mariana; Gobin, Pierre; Abramson, David H.; Chantada, Guillermo; Schaiquevich, Paula

    2016-01-01

    Extraocular retinoblastoma is a major challenge worldwide, especially in developing countries. Current treatment involves the administration of systemic chemotherapy combined with radiation, but there is a clear need for improvement of chemotherapy bioavailability in the optic nerve. Our aim was to study the ophthalmic artery chemosurgery (OAC) local route for drug delivery assessing ocular and optic nerve exposure to chemotherapy and to compare it to exposure after intravenous infusion (IV) of the same dose in an animal model. Topotecan was used as a prototype drug that is active in retinoblastoma and based on the extensive knowledge of its pharmacokinetics in preclinical and clinical settings. Five Landrace pigs received 4mg of topotecan via OAC as performed in retinoblastoma patients. At the end of the infusion, the eyes were enucleated, the optic nerve and retina were dissected, and the vitreous and plasma were separated. After recovery and a wash-out period, the animals received a 30-min IV infusion of topotecan (4 mg). The remaining eye was enucleated and tissues and fluids were separated. All samples were stored until quantitation using HPLC. A significantly higher concentration of topotecan in the optic nerve, vitreous, and retina was obtained in eyes after OAC compared to IV infusion (p<0.05). The median (range) ratio between topotecan concentration attained after OAC to IV infusion in the optic nerve, retina and vitreous was 84(54–668), 143(49–200) and 246(56–687), respectively. However, topotecan systemic exposure after OAC and IV infusion remained comparable (p>0.05). The median optic nerve-to-plasma ratio after OAC and IV was 44 and 0.35, respectively. Topotecan OAC delivery attained an 80-fold higher concentration in the optic nerve compared to the systemic infusion of the same dose with similar plasma concentrations in a swine model. Patients with retinoblastoma extension into the optic nerve may benefit from OAC for tumor burden by increased

  10. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow

    PubMed Central

    Vodstrcil, Lenka A.; Tare, Marianne; Novak, Jacqueline; Dragomir, Nicoleta; Ramirez, Rolando J.; Wlodek, Mary E.; Conrad, Kirk P.; Parry, Laura J.

    2012-01-01

    Normal pregnancy involves dramatic remodeling of the uterine vasculature, with abnormal vascular adaptations contributing to pregnancy diseases such as preeclampsia. The peptide hormone relaxin is important for the renal and systemic hemodynamic adaptations to pregnancy, and has been shown to increase arterial compliance and outward hypertrophic remodeling. Therefore, we investigated the possibility that relaxin acts on its receptor, RXFP1, to mediate uterine artery compliance in late pregnancy and increase uterine blood flow velocity in rats. RXFP1 was predominantly localized to the tunica media vascular smooth muscle cells in the uterine artery, although receptors were also detected in endothelial cells. Highest expression of Rxfp1 in the uterine artery occurred in estrus and early pregnancy. Isolated uterine arteries from late pregnant rats treated with a monoclonal antibody against circulating relaxin (MCA1) had significantly increased vessel wall stiffness compared with controls, with no reduction in wall thickness. Chronic infusion of relaxin (4 μg/h, osmotic minipump) for 5 d in nonpregnant rats significantly increased uterine artery blood flow velocity. Overall, these data demonstrate a functional role for relaxin in mediating uterine artery compliance in pregnant rats, which may be necessary to maintain adequate uterine blood flow to the uterus and placenta.—Vodstrcil, L. A., Tare, M., Novak, J., Dragomir, N., Ramirez, R. J., Wlodek, M. E., Conrad, K. P., Parry, L. J. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow. PMID:22744867

  11. Failure of atriopeptin II to cause arterial vasodilation in the conscious rat.

    PubMed

    Lappe, R W; Smits, J F; Todt, J A; Debets, J J; Wendt, R L

    1985-04-01

    The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow, or with an electromagnetic flow probe on the ascending aorta to facilitate the measurement of cardiac output in the conscious rat. Intravenous infusion of increasing doses of atriopeptin II (0.25-4 micrograms/kg per min) caused a dose-dependent fall in mean arterial pressure in the hypertensive and normotensive rats. Blood flow in the renal, mesenteric, and hindquarters vascular beds was markedly decreased during the infusion of atriopeptin II, and regional vascular resistance was significantly increased in both groups of rats. Heart rate was significantly elevated (47 +/- 14 beats/min) in the spontaneously hypertensive rats during atriopeptin II infusion, but no change in heart rate was observed in the Wistar rats. In the hypertensive rats, atriopeptin II caused a marked dose-dependent decrease in cardiac output (maximal decrease = -39 +/- 4%) and stroke volume (maximal decrease = -48 +/- 4%). Central venous pressure and left atrial pressure were also significantly reduced during atriopeptin II infusion. Total peripheral resistance was increased over the infusion protocol by 26 +/- 3%. These data suggest that atriopeptin II infusion markedly attenuated cardiac output in the conscious spontaneously hypertensive rats. Total and regional vascular resistances were increased, possibly through reflex compensatory mechanisms, to maintain arterial pressure in the face of decreased cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Computational drug repositioning for peripheral arterial disease: prediction of anti-inflammatory and pro-angiogenic therapeutics

    PubMed Central

    Chu, Liang-Hui; Annex, Brian H.; Popel, Aleksander S.

    2015-01-01

    Peripheral arterial disease (PAD) results from atherosclerosis that leads to blocked arteries and reduced blood flow, most commonly in the arteries of the legs. PAD clinical trials to induce angiogenesis to improve blood flow conducted in the last decade have not succeeded. We have recently constructed PADPIN, protein-protein interaction network (PIN) of PAD, and here we combine it with the drug-target relations to identify potential drug targets for PAD. Specifically, the proteins in the PADPIN were classified as belonging to the angiome, immunome, and arteriome, characterizing the processes of angiogenesis, immune response/inflammation, and arteriogenesis, respectively. Using the network-based approach we predict the candidate drugs for repositioning that have potential applications to PAD. By compiling the drug information in two drug databases DrugBank and PharmGKB, we predict FDA-approved drugs whose targets are the proteins annotated as anti-angiogenic and pro-inflammatory, respectively. Examples of pro-angiogenic drugs are carvedilol and urokinase. Examples of anti-inflammatory drugs are ACE inhibitors and maraviroc. This is the first computational drug repositioning study for PAD. PMID:26379552

  13. Complications of Elastase-Induced Arterial Saccular Aneurysm in Rabbits: Case Reports and Literature Review

    PubMed Central

    Villano, Jason S; Boehm, Christine A; Carney, Elizabeth L; Cooper, Timothy K

    2012-01-01

    Endoluminal infusion and incubation of elastase with or without collagenase into the rabbit common carotid artery is an established model of arterial saccular aneurysm. The model mimics naturally occurring human cerebral aneurysms in many ways, including histologic and morphologic characteristics, hemodynamic pressures, and shear stresses. However, complications have been associated with the model. Here, we report 2 complications: 1) the first known case of iatrogenic laryngeal hemiplegia in a rabbit; and 2) histopathologically confirmed iatrogenic hippocampal and cerebellar infarcts (stroke). Finally, we present and review data from current literature on the morbidity and mortality associated with this model. PMID:23561881

  14. Comparison of Prophylactic Infusion of Phenylephrine with Ephedrine for Prevention of Hypotension in Elective Cesarean Section under Spinal Anesthesi: A Randomized Clinical Trial

    PubMed Central

    Moslemi, Farnaz; Rasooli, Sousan

    2015-01-01

    Background Spinal anesthesia is an accepted technique in elective cesarean sections. However, hypotension, resulted from sympathectomy is a common problem, especially in pregnant women. Prevention of this complication by sympathomimetic agents is of potential clinical significance. The aim of this study is to compare the effect of prophylactic infusion of Phenylephrine versus Ephedrine in the prevention of hypotension during spinal anesthesia in elective cesarean section. Methods Eighty-three patients were enrolled in this study and randomly divided into three groups. Group Ph received phenylephrine infusion, group E received ephedrine infusion while group P were delivered placebo. Vital signs (blood pressure, heart rate, and arterial oxygen saturation) were recorded throughout the surgery. Maternal and neonatal perioperative complications were also controlled and recorded. Results There was an insignificant difference in demographic data between the groups. Systolic and diastolic blood pressures were higher in the phenylephrine group than control, but not higher than the ephedrine group. Maternal dysrhythmias were more common in ephedrine and phenylephrine groups than the control group. Vomiting was more common in ephedrine group (P<0.05). In addition, the fifth-minute Apgar score of neonates was higher in phenylephrine and ephedrine groups than the control group (P<0.05). Neonates of phenylephrine group had less acidosis than the other groups. Conclusion Prophylactic infusion of phenylephrine can effectively decrease spinal anesthesia related hypotension without any significant complication for mother or her fetus. Trial Registration Number: IRCT2012120911700N1 PMID:25649721

  15. Arterial Chemoradiotherapy for Locally Advanced Tongue Cancer: Analysis of Retrospective Study of Therapeutic Results in 88 Patients

    SciTech Connect

    Fuwa, Nobukazu Kodaira, Takesi; Furutani, Kazuhisa; Tachibana, Hiroyuki; Nakamura, Tatsuya; Nakahara, Rie; Tomoda, Takuya; Inokuti, Haruo; Daimon, Takashi

    2008-11-15

    Purpose: To retrospectively investigate the therapeutic results of arterial injection therapy by way of the superficial temporal artery for 88 cases of Stage III and IV (M0) tongue cancer and to clarify the factors that affected the therapeutic results. Methods and Materials: We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 39 patients between January 1993 and July 2002. Systemic concurrent chemotherapy was given to 19 of these patients. We administered intra-arterial chemoradiotherapy with cisplatin with sodium thiosulfate to 49 patients between October 2002 and December 2006. Concurrent systemic chemotherapy was given to 38 of these patients. Results: The 3-year local control rate was 72% (T2-T3, 80%; and T4, 48%), and the 3-year survival rate was 57% (Stage III, 67%; Stage IV, 43%). On univariate analysis, age, T stage, N stage, overall stage, systemic chemotherapy, difference in intra-arterial chemotherapy, and performance status had a significant effect on survival. On multivariate analysis, N stage, systemic chemotherapy, difference in intra-arterial chemotherapy, and artery selected had a significant effect on survival. Conclusions: The therapeutic results of intra-arterial chemoradiotherapy using the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy using cisplatin with sodium thiosulfate were excellent, and we believe it will be a new therapy for advanced tongue cancer.

  16. Effects of adenosine infusion into renal interstitium on renal hemodynamics

    SciTech Connect

    Pawlowska, D.; Granger, J.P.; Knox, F.G.

    1987-04-01

    This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. In fusion of adenosine decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), decreased GFR from 0.73 +/- 0.07 to 021 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, (/sup 3/H)NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. They conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their