Evolution of hemostatic agents in surgical practice

PubMed Central

Sundaram, Chandru P.; Keenan, Alison C.

2010-01-01

Objective: Topical hemostatic agents are used in a wide variety of surgical settings, and the evolution of this class of surgical tools is an interesting topic. We reviewed and outlined the historical progress of topical hemostats into present day surgery and urology, and highlight opportunities for future research. Materials and Methods: A MEDLINE search of all available literature concerning several classes of topical hemostatic agents was performed. Fibrins sealants, Gelatin sponge hemostatics, cyanoacrylate adhesives, oxidized regenerated cellulose, and microfibrillar collagen were included. References were chosen from a broad range of surgical literature. Results: Topical hemostatic agents have historically taken advantage of a wide variety of mechanisms for hemostasis. Fibrin sealants have a rich history and large potential for further applications. Gelatin sponge hemostatics have been widely used since their introduction, but have changed little. Cyanoacrylate adhesives have a unique mechanism and opportunity for novel applications of existing products. Oxidized cellulose was original in the use of plant-based components. Microfibrillar collagen hemostats have evolved to a wide variety of formats. Conclusions: A review of the evolution of topical hemostatic agents highlights opportunities for potential novel research. Fibrin sealants may have the most opportunity for advancement, and understanding the history of these products is useful. With the drive in urology for minimally invasive surgical techniques, adaptation of topical hemostatic agents to this surgical approach would be valuable and offers an opportunity for novel contributions. PMID:21116358

Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory Biomarkers in the Multi-Ethnic Study of Atherosclerosis

PubMed Central

Cushman, Mary; Jenny, Nancy; Michos, Erin D.; Smith, Nicholas L.; Kestenbaum, Bryan; de Boer, Ian H.

2016-01-01

Context: Mechanisms explaining documented associations of 25-hydroxyvitamin D [25(OH)D] deficiency with increased risks of cardiovascular disease (CVD) and venous thromboembolism may relate to adverse hemostatic and inflammatory responses. Objective: To evaluate whether 25(OH)D deficiency is associated with a prothrombotic and proinflammatory biological profile. Design: Cross-sectional analyses. Setting: The Multi-Ethnic Study of Atherosclerosis, a multicenter prospective cohort of American adults. Participants: Up to 6554 adults free of CVD. Main Outcome Measures: Ten hemostatic biomarkers (D-dimer, fibrinogen, factor VIII, plasmin-antiplasmin, and homocysteine [n = 6443]; von Willebrand factor, soluble tissue factor, plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (TFPI), and soluble thrombomodulin [n = 814]), and three inflammatory biomarkers (IL-6, C-reactive protein [n = 6443], and TNF-α soluble receptor [n = 3802]). Results: Among 6443 subjects (46.6% men; mean age, 62.1 years; mean body mass index, 28.3 kg/m2) of White (37.8%), Black (27.2%), Chinese (12.2%), and Hispanic (21.8%) race/ethnicity, mean 25(OH)D was 25.3 ng/mL. After multiple adjustment, 25(OH)D concentrations were associated with concentrations of IL-6 and homocysteine and also with concentrations of PAI-1 and TFPI: per 10 ng/mL decrement in 25(OH)D, 5.1% higher IL-6 (95% confidence interval [CI], 3.4–6.9; P < .001); 3.7% higher homocysteine (95% CI, 3.0–4.3; P < .001); 7.0% higher PAI-1 (95% CI, 0.9–13.6; P = .025); and 2.1% higher TFPI (95% CI, 0.0–4.2; P = .047), without racial/ethnic heterogeneity. No significant associations were observed for other hemostatic and inflammatory biomarkers. Conclusions: Increased inflammation as reflected by higher circulating IL-6 and increased homocysteine concentrations may represent mechanisms linking 25(OH)D deficiency to greater risks of CVD and perhaps venous thromboembolism. Low concentrations of 25(OH)D were also associated with PAI-1 and TFPI concentrations, but not with other hemostatic biomarkers. PMID:27023449

Basic in vitro experiment on the adhesive effects of sheet-type hemostatic agents used in combination with a liquid fibrin sealant.

PubMed

Ishii, Keiichi; Kawashima, Hideki; Hayama, Takuma; Mayabashira, Sumika; Oka, Shiro; Sugimoto, Toshikado

2011-11-01

Various hemostatic agents have been used quite effectively for hemostasis, as well as for providing effective adhesion during laparoscopic partial nephrectomies. In this study, we investigated the adhesiveness to the renal tissue of some sheet-type hemostatic agents used in combination with a liquid fibrin sealant. In Experiment A, component solutions of the fibrin glue (liquid fibrin sealant) were dripped onto a kite string placed annularly on a porcine kidney slice. Then, one of the sheet-type hemostats--namely, the collagen, gelatin, or cellulose hemostat--was placed on the slices, and a string scale was used to measure the force needed to pull the string apart vertically from the kidney slice. Twelve slices were used for each group, and the weight data were analyzed statistically. The tissue adhering to each sheet-type hemostatic agent was fixed in formalin and sliced and then examined by light microscopy after hematoxylin and eosin staining. In Experiment B, the solutions were dripped onto the sheet-type hemostatic agent placed first on the slice, and the force needed for pulling apart the hemostat sheet from the slice was similarly examined. The combination of fibrin glue plus a collagen hemostat was clearly superior in Experiment A, but the hemostat and renal tissue could be pulled apart more easily in Experiment B. These results showed that fibrin glue could not exert its expected adhesive effect unless it is used in combination with another hemostatic agent or is directly applied to renal tissue. It is important to obtain further comparative data among agents and select the appropriate agents, taking into consideration the type of surgery.

COMBAT: Initial experience with a randomized clinical trial of plasma-based resuscitation in the field for traumatic hemorrhagic shock

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Chin, Theresa L; Ghasabyan, Arsen; Chandler, James; Stringham, John; Gonzalez, Eduardo; Moore, Hunter B.; Banerjee, Anirban; Silliman, Christopher C; Sauaia, Angela

2015-01-01

The existing evidence shows great promise for plasma as the first resuscitation fluid in both civilian and military trauma. We embarked on the Control of Major Bleeding After Trauma (COMBAT) trial with the support of the Department of Defense, in order to determine if plasma-first resuscitation yields hemostatic and survival benefits. The methodology of the COMBAT study represents not only three years of development work, but the integration of nearly two-decades of technical experience with the design and implementation of other clinical trials and studies. Herein, we describe the key features of the study design, critical personnel and infrastructural elements, and key innovations. We will also briefly outline the systems engineering challenges entailed by this study. COMBAT is a randomized, placebo controlled, semi-blinded prospective Phase IIB clinical trial, conducted in a ground ambulance fleet based at a Level I trauma center, and part of a multicenter collaboration. The primary objective of COMBAT is to determine the efficacy of field resuscitation with plasma first, compared to standard of care (normal saline). To date we have enrolled 30 subjects in the COMBAT study. The ability to achieve intervention with a hemostatic resuscitation agent in the closest possible temporal proximity to injury is critical and represents an opportunity to forestall the evolution of the “bloody vicious cycle”. Thus, the COMBAT model for deploying plasma in first response units should serve as a model for RCTs of other hemostatic resuscitative agents. PMID:25784527

Comparison of hemostatic matrix and standard hemostasis in patients undergoing primary TKA.

PubMed

Comadoll, James L; Comadoll, Shea; Hutchcraft, Audrey; Krishnan, Sangeeta; Farrell, Kelly; Kreuwel, Huub T C; Bechter, Mark

2012-06-01

Bleeding after total knee arthroplasty increases the risk of pain, delayed rehabilitation, blood transfusion, and transfusion-associated complications. The authors compared pre- and postoperative decreases in hemoglobin as a surrogate for blood loss in consecutive patients treated at a single institution by the same surgeon (J.L.C.) using conventional hemostatic methods (electrocautery, suturing, or manual compression) or a gelatin and thrombin-based hemostatic matrix during total knee arthroplasty. Data were collected retrospectively by chart review. The population comprised 165 controls and 184 patients treated with hemostatic matrix. Median age was 66 years (range, 28-89 years); 66% were women. The arithmetic mean ± SD for the maximal postoperative decrease in hemoglobin was 3.18 ± 0.94 g/dL for controls and 2.19 ± 0.83 g/dL for the hemostatic matrix group. Least squares means estimates of the group difference (controls-hemostatic matrix) in the maximal decrease in hemoglobin was 0.96 g/dL (95% confidence interval, 0.77-1.14 mg/dL; P<.0001). Statistically significant covariate effects were observed for preoperative hemoglobin level (P<.0001) and body mass index (P=.0029). Transfusions were infrequent in both groups. The frequency of acceptable range of motion was high (control, 88%; hemostatic matrix, 84%). In both groups, overall mean tourniquet time was approximately 1 hour, and the most common length of stay was 3 to 5 days. No serious complications related to the hemostatic agent were observed. These data demonstrate that the use of a flowable hemostatic matrix results in less reduction in hemoglobin than the use of conventional hemostatic methods in patient undergoing total knee arthroplasty. Copyright 2012, SLACK Incorporated.

New hemostatic agents in the combat setting.

PubMed

Cox, E Darrin; Schreiber, Martin A; McManus, John; Wade, Charles E; Holcomb, John B

2009-12-01

Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma patients. Animal data have shown that hemostatic bandages reduce hemorrhage and improve survival. This article reports recent clinical observations regarding the efficacy and evolution of use of two new hemostatic bandages employed in the global war on terrorism. We performed a retrospective cohort review of soldiers treated with either the QuikClot or HemCon hemostatic bandages between April and October 2006. Hemostatic dressings were placed on wounds either in the field or at the combat support hospital (CSH). During the 6-month study period, 1691 trauma patients were admitted to the CSH. Fifty uses of hemostatic dressings in 44 patients (2.6% of admissions) were identified. Forty patients were treated with HemCon dressings, three patients with QuikClot, and one with both QuikClot and HemCon. Eighteen percent of the dressings were used in the field, predominantly on extremity wounds (7/8). In contrast, most dressings used in the CSH were for truncal wounds (26/36 patients). Hemostatic dressings were applied to extremity wounds in prehospital and hospital settings, either alone or in conjunction with tourniquets. In surviving patients (95%), the treating surgeon determined that the hemorrhage was either stopped or greatly decreased by use of hemostatic dressings. Two of the four patients treated with QuikClot had burns from exothermic reactions, while no adverse reactions were noted with HemCon. Hemostatic agents stop or decrease bleeding. Whereas HemCon appears to be safe, QuikClot may produce superficial burns. These new hemostatic agents have a place in the surgical armamentarium to assist in controlling internal hemorrhage from truncal and pelvic hemorrhage, especially during damage-control surgery.

GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis.

PubMed

Law, Luke A; Graham, Douglas K; Di Paola, Jorge; Branchford, Brian R

2018-01-01

The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. Transgenic mice deficient in GAS6, or any of the TAM family of receptors that engage this ligand, exhibit in vivo protection against arterial and venous thrombosis but do not demonstrate either spontaneous or prolonged bleeding compared to their wild-type counterparts. Comparable results are observed in wild-type mice treated with pharmacological inhibitors of the GAS6-TAM pathway. Thus, GAS6/TAM inhibition offers an attractive novel therapeutic option that may allow for a moderate reduction in platelet activation and decreased thrombosis while still permitting the primary hemostatic function of platelet plug formation.

77 FR 64311 - Foreign-Trade Zone 176-Rockford, IL, Notification of Proposed Production Activity, AndersonBrecon...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-19

... procedures that applies to SURGIFLO[supreg] Hemostatic Matrix Kits and SURGIFLO[supreg] Hemostatic Matrix... from abroad include: Sterile water in vials/non-needled syringes, hemostatic gelatin matrix pouches...

In vitro analysis of polyurethane foam as a topical hemostatic agent.

PubMed

Broekema, Ferdinand I; van Oeveren, Wim; Zuidema, Johan; Visscher, Susan H; Bos, Rudolf R M

2011-04-01

Topical hemostatic agents can be used to treat problematic bleedings in patients who undergo surgery. Widely used are the collagen- and gelatin-based hemostats. This study aimed to develop a fully synthetic, biodegradable hemostatic agent to avoid exposure to animal antigens. In this in vitro study the suitability of different newly developed polyurethane-based foams as a hemostatic agent has been evaluated and compared to commonly used agents. An experimental in vitro test model was used in which human blood flowed through the test material. Different modified polyurethane foams were compared to collagen and gelatin. The best coagulation was achieved with collagen. The results of the polyurethane foam improved significantly by increasing the amount of polyethylene glycol. Therefore, the increase of the PEG concentration seems a promising approach. Additional in vivo studies will have to be implemented to assess the application of polyurethane foam as a topical hemostatic agent.

Safety biocompatibility of gelatin hemostatic matrix (Floseal and Surgiflo) in neurosurgical procedures.

PubMed

Gazzeri, Roberto; Galarza, Marcelo; Alfier, Alex

2012-12-01

Adequate hemostasis in cranial and spinal surgery is of paramount importance in a neurosurgeon's daily practice. Generalized ooze bleeding from the surgical wall cavities, coming from the dura mater or nervous tissue may be troublesome and may limit visualization in minimally invasive neurosurgery. Hemostatic matrix is a mixture of a flowable gelatin matrix (bovine or porcine) and a thrombin component mixed together. A total of 318 patients undergoing cranial, craniospinal, and spinal procedure with the use of gelatin hemostatic matrix (Floseal and Surgiflo) were enrolled in this clinical study. We compared the different hemostatic techniques using the gelatin hemostatic matrix, and investigated indications, time to bleeding control, and its efficacy and safety in neurosurgery.

Isolation, Characterization and Evaluation of Collagen from Jellyfish Rhopilema esculentum Kishinouye for Use in Hemostatic Applications.

PubMed

Cheng, Xiaochen; Shao, Ziyu; Li, Chengbo; Yu, Lejun; Raja, Mazhar Ali; Liu, Chenguang

2017-01-01

Hemostat has been a crucial focus since human body is unable to control massive blood loss, and collagen proves to be an effective hemostat in previous studies. In this study, collagen was isolated from the mesoglea of jellyfish Rhopilema esculentum Kishinouye and its hemostatic property was studied. The yields of acid-soluble collagen (ASC) and pepsin-soluble (PSC) were 0.12% and 0.28% respectively. The SDS-PAGE patterns indicated that the collagen extracted from jellyfish mesoglea was type I collagen. The lyophilized jellyfish collagen sponges were cross-linked with EDC and interconnected networks in the sponges were revealed by scanning electron microscope (SEM). Collagen sponges exhibited higher water absorption rates than medical gauze and EDC/NHS cross-linking method could improve the stability of the collagen sponges. Compared with medical gauze groups, the blood clotting indexes (BCIs) of collagen sponges were significantly decreased (P < 0.05) and the concentration of collagen also had an influence on the hemostatic property (P < 0.05). Collagen sponges had an improved hemostatic ability compared to the gauze control in tail amputation rat models. Hemostatic mechanism studies showed that hemocytes and platelets could adhere and aggregate on the surface of collagen sponge. All properties make jellyfish collagen sponge to be a suitable candidate used as hemostatic material and for wound healing applications.

Isolation, Characterization and Evaluation of Collagen from Jellyfish Rhopilema esculentum Kishinouye for Use in Hemostatic Applications

PubMed Central

Cheng, Xiaochen; Liu, Chenguang

2017-01-01

Hemostat has been a crucial focus since human body is unable to control massive blood loss, and collagen proves to be an effective hemostat in previous studies. In this study, collagen was isolated from the mesoglea of jellyfish Rhopilema esculentum Kishinouye and its hemostatic property was studied. The yields of acid-soluble collagen (ASC) and pepsin-soluble (PSC) were 0.12% and 0.28% respectively. The SDS-PAGE patterns indicated that the collagen extracted from jellyfish mesoglea was type I collagen. The lyophilized jellyfish collagen sponges were cross-linked with EDC and interconnected networks in the sponges were revealed by scanning electron microscope (SEM). Collagen sponges exhibited higher water absorption rates than medical gauze and EDC/NHS cross-linking method could improve the stability of the collagen sponges. Compared with medical gauze groups, the blood clotting indexes (BCIs) of collagen sponges were significantly decreased (P < 0.05) and the concentration of collagen also had an influence on the hemostatic property (P < 0.05). Collagen sponges had an improved hemostatic ability compared to the gauze control in tail amputation rat models. Hemostatic mechanism studies showed that hemocytes and platelets could adhere and aggregate on the surface of collagen sponge. All properties make jellyfish collagen sponge to be a suitable candidate used as hemostatic material and for wound healing applications. PMID:28103327

Next Generation Hemostatic Materials Based on NHS-Ester Functionalized Poly(2-oxazoline)s.

PubMed

Boerman, Marcel A; Roozen, Edwin; Sánchez-Fernández, María José; Keereweer, Abraham R; Félix Lanao, Rosa P; Bender, Johan C M E; Hoogenboom, Richard; Leeuwenburgh, Sander C; Jansen, John A; Van Goor, Harry; Van Hest, Jan C M

2017-08-14

In order to prevent hemorrhage during surgical procedures, a wide range of hemostatic agents have been developed. However, their efficacy is variable; hemostatic devices that use bioactive components to accelerate coagulation are dependent on natural sources, which limits reproducibility. Hybrid devices in which chain-end reactive poly(ethylene glycol) is employed as active component sometimes suffer from irregular cross-linking and dissolution of the polar PEG when blood flow is substantial. Herein, we describe a synthetic, nonbioactive hemostatic product by coating N-hydroxysuccinimide ester (NHS)-functional poly(2-oxazoline)s (POx-NHS) onto gelatin patches, which acts by formation of covalent cross-links between polymer, host blood proteins, gelatin and tissue to seal the wound site and prevent hemorrhage during surgery. We studied different process parameters (including polymer, carrier, and coating technique) in direct comparison with clinical products (Hemopatch and Tachosil) to obtain deeper understanding of this class of hemostatic products. In this work, we successfully prove the hemostatic efficacy of POx-NHS as polymer powders and coated patches both in vitro and in vivo against Hemopatch and Tachosil, demonstrating that POx-NHS are excellent candidate polymers for the development of next generation hemostatic patches.

Hemostatic action of polyurethane foam with 55% polyethylene glycol compared to collagen and gelatin.

PubMed

Broekema, Ferdinand I; van Oeveren, Wim; Boerendonk, Andrea; Sharma, Prashant K; Bos, Rudolf R M

2016-08-12

For most topical hemostatic agents the mechanism of hemostatic action is not fully understood. This work aimed to investigate the hemostatic mechanism of action and viscoelastic properties of polyurethane foam (PU) in comparison to the widely used collagen and gelatin. The hemostatic mechanism of action of the materials was tested using human whole blood and platelet-poor plasma (PPP). The ability of the hemostatic agent to exert pressure on the wound was quantified in terms of its viscoelastic properties both under dry and wet conditions using a low load compression tester (LLCT). It has been shown that collagen and PU initiate hemostasis through both thrombocyte aggregation and contact activation of the coagulation cascade. Gelatin did not show improved thrombocyte aggregation or initiation of the coagulation cascade compared to the negative control group. PU is more firm under wet conditions and shows more springback than collagen and gelatin. We conclude that PU is promising as a topical hemostatic agent because it initiates both the coagulation cascade and thrombocyte aggregation. Furthermore, it has favorable viscoelastic properties compared to collagen and gelatin which leads to increased pressure on a wound.

Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study

PubMed Central

Schutz, Charlotte; Ward, Amy M.; Huson, Mischa A. M.; Wilkinson, Robert J.; Burton, Rosie; Maartens, Gary; Wilkinson, Katalin A.; Meijers, Joost C. M.; Lutter, René; Grobusch, Martin P.; Meintjes, Graeme; van der Poll, Tom

2017-01-01

Background Mortality rates remain high for human immunodeficiency virus (HIV)–associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects. Methods We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates. Results Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0–24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality. Conclusions Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality. PMID:28363198

Emerging roles for hemostatic dysfunction in malaria pathogenesis.

PubMed

O'Sullivan, Jamie M; Preston, Roger J S; O'Regan, Niamh; O'Donnell, James S

2016-05-12

Severe Plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-Saharan Africa where it accounts for up to 1 million deaths per annum. In spite of the significant mortality and morbidity associated with cerebral malaria (CM), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. Previous studies have demonstrated that sequestration of P falciparum-infected erythrocytes within the microvasculature of the brain plays a key role in the development of CM. In addition, there is convincing evidence that both endothelial cell activation and platelets play critical roles in the modulating the pathogenesis of severe P falciparum malaria. In this review, we provide an overview of recent studies that have identified novel roles through which hemostatic dysfunction may directly influence malaria pathogenesis. In particular, we focus on emerging data suggesting that von Willebrand factor, coagulation cascade activation, and dysfunction of the protein C pathway may be of specific importance in this context. These collective insights underscore a growing appreciation of the important, but poorly understood, role of hemostatic dysfunction in malaria progression and, importantly, illuminate potential approaches for novel therapeutic strategies. Given that the mortality rate associated with CM remains on the order of 20% despite the availability of effective antimalarial therapy, development of adjunctive therapies that can attenuate CM progression clearly represents a major unmet need. These emerging data are thus not only of basic scientific interest, but also of direct clinical significance. © 2016 by The American Society of Hematology.

Gene Variations in the Protein C and Fibrinolytic Pathway: Relevance for Severity and Outcome in Pediatric Sepsis.

PubMed

Boeddha, Navin P; Emonts, Marieke; Cnossen, Marjon H; de Maat, Moniek P; Leebeek, Frank W; Driessen, Gertjan J; Hazelzet, Jan A

2017-02-01

The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. Deregulation of hemostasis and fibrinolysis are major causes of critical illness and important determinants of outcome in severe sepsis. The hemostatic responses to infection vary widely between individuals, and are in part explained by polymorphisms in genes responsible for the protein C and fibrinolytic pathway. This review gives an overview of genetic polymorphisms in the protein C and fibrinolytic pathway associated with susceptibility and severity of pediatric sepsis. In addition, genetic polymorphisms associated with adult sepsis and other pediatric thromboembolic disorders are discussed, as these polymorphisms might be candidates for future molecular genetic research in pediatric sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

In vivo hemostatic efficacy of polyurethane foam compared to collagen and gelatin.

PubMed

Broekema, Ferdinand I; van Oeveren, Wim; Selten, Maaike H A; Meijer, Rolf J H; de Wolf, Joost T M; Bos, Rudolf R M

2013-05-01

Topical hemostatic agents are used in all surgical disciplines. Most of these hemostats are based on animal-derived products like collagen and gelatin. They carry the potential risk of pathogen transmission. A newly developed biodegradable, fully synthetic hemostatic agent based on polyurethane foam (PU) with 55 % polyethylene glycol (PEG) would prevent these potential risks. The hemostatic efficacy of this new agent was compared to gelatin and collagen in humans who underwent extraction of an upper and lower molar (split-mouth model). After extraction of a molar in the maxilla and mandible, a PU foam and collagen or gelatin were inserted in the extraction socket for 2 min. Hereafter, the agents were removed and stored in ethylenediaminetetraacetic acid to stop coagulation. Then, the concentration of coagulation parameters thrombin-antithrombin III (TAT) complexes, fibrinogen, and thromboxane B2 (TxB2) in blood extracts from the agents was measured. The concentrations were also determined in baseline blood samples which were collected from the extraction socket. The concentrations of TAT and TxB2 were significantly increased, and fibrinogen concentration was significantly reduced compared to baseline wound blood concentrations indicating enhanced hemostasis. No significant differences were seen in the concentrations of these coagulation parameters in the three different hemostatic agents. These results show that PU combined with 55 % PEG is a promising alternative for the animal-derived hemostatic agents. The synthetic hemostatic agent could replace the animal-derived products like collagen and gelatin and therewith prevent the potential risk of pathogen transmission.

Ex-vivo porcine organs with a circulation pump are effective for teaching hemostatic skills

PubMed Central

2012-01-01

Surgical residents have insufficient opportunites to learn basic hemostatic skills from clinical experience alone. We designed an ex-vivo training system using porcine organs and a circulation pump to teach hemostatic skills. Residents were surveyed before and after the training and showed significant improvement in their self-confidence (1.83 ± 1.05 vs 3.33 ± 0.87, P < 0.01) on a 5 point Likert scale. This training may be effective to educate residents in basic hemostatic skills. PMID:22404974

Comparison of transcutaneous contrast-enhanced ultrasound-guided injected hemostatic agents with traditional surgery treatment for liver, spleen and kidney trauma: a retrospective study.

PubMed

Wang, Dong; Lv, Faqin; Luo, Yukun; An, Lichun; Li, Junlai; Xie, Xia; Tian, Jiangke; Zhao, Weiyan; Tang, Jie

2012-10-01

There is lack of studies on the effectiveness of transcutaneous contrast-enhanced ultrasound-guided injections of hemostatic agents for liver. spleen and kidney trauma. We compared treatment by hemostatic agents to surgical treatment in a retrospective interventional human study. The study enrolled a total of 135 subjects from emergency unit of the Chinese People's Liberation Army General Hospital in Beijing. Within the cohort, 62 patients received contrast enhanced ultrasound-guided injection of hemostatic agents and the rest received surgical treatments. The injury severity score was lower in the hemostatic agent treatment group than surgical treatment group (p<0.05), but Glasgow coma scale scores did not reach statistical significance. The patients in the surgical treatment group had significantly higher hospital fees than those in the hemostatic treatment group (p<0.05), although the length of hospitalization did not significantly differ between two groups. Safety outcome variables pre- and post-treatment remained within normal limits in both groups. Hemostatic agents were more cost-effective than surgery to treat patients with liver, spleen and kidney trauma. However, given the limited sample size, subsequent studies drawing upon larger populations from multiple medical centers are necessary for follow-up.

A randomized, controlled trial of Veriset™ hemostatic patch in halting cardiovascular bleeding.

PubMed

Glineur, David; Hendrikx, Marc; Krievins, Dainis; Stradins, Peteris; Voss, Bernhard; Waldow, Thomas; Haenen, Luc; Oberhoffer, Martin; Ritchie, Caroline M

2018-01-01

Obtaining hemostasis during cardiovascular procedures can be a challenge, particularly around areas with a complex geometry or that are difficult to access. While several topical hemostats are currently on the market, most have caveats that limit their use in certain clinical scenarios such as pulsatile arterial bleeding. The aim of this study was to assess the effectiveness and safety of Veriset™ hemostatic patch in treating cardiovascular bleeding. Patients (N=90) scheduled for cardiac or vascular surgery at 12 European institutions were randomized 1:1 to treatment with either Veriset™ hemostatic patch (investigational device) or TachoSil ® (control). After application of the hemostat, according to manufacturer instructions for use, time to hemostasis was monitored. Follow-up occurred up to 90 days post-surgery. Median time to hemostasis was 1.5 min with Veriset™ hemostatic patch, compared to 3.0 min with TachoSil ® ( p <0.0001). Serious adverse events within 30 days post-surgery were experienced by 12/44 (27.3%) patients treated with Veriset™ hemostatic patch and 10/45 (22.2%) in the TachoSil ® group ( p =0.6295). None of these adverse events were device-related, and no reoperations for bleeding were required within 5 days post-surgery in either treatment group. This study reinforces the difference in minimum recommended application time between Veriset™ hemostatic patch and TachoSil ® (30 s versus 3 min respectively). When compared directly at 3 min, Veriset™ displayed no significant difference, showing similar hemostasis and safety profiles on the cardiovascular bleeding sites included in this study.

Incidence of thromboembolic events after use of gelatin-thrombin-based hemostatic matrix during intracranial tumor surgery.

PubMed

Gazzeri, Roberto; Galarza, Marcelo; Conti, Carlo; De Bonis, Costanzo

2018-01-01

Association between the use of hemostatic agents made from collagen/gelatin mixed with thrombin and thromboembolic events in patients undergoing tumor resection has been suggested. This study evaluates the relationship between flowable hemostatic matrix and deep vein thrombosis in a large cohort of patients treated for brain tumor removal. The authors conducted a retrospective, multicenter, clinical review of all craniotomies for tumor removal performed between 2013 and 2014. Patients were classified in three groups: group I (flowable gelatin hemostatic matrix with thrombin), group II (gelatin hemostatic without thrombin), and group III (classical hemostatic). A total of 932 patients were selected: tumor pathology included 441 gliomas, 296 meningiomas, and 195 metastases. Thromboembolic events were identified in 4.7% of patients in which gelatin matrix with thrombin was applied, in 8.4% of patients with gelatin matrix without thrombin, and in 3.6% of cases with classical methods of hemostasis. Patients with venous thromboembolism had an increased proportion of high-grade gliomas (7.2%). Patients receiving a greater dose than 10 ml gelatin hemostatic had a higher rate of thromboembolic events. Intracranial hematoma requiring reintervention occurred in 19 cases: 4.5% of cases of group III, while reoperation was performed in 1.3 and 1.6% of patients in which gelatin matrix with or without thrombin was applied. Gelatin matrix hemostat is an efficacious tool for neurosurgeons in cases of difficult intraoperative bleeding during cranial tumor surgery. This study may help to identify those patients at high risk for developing thromboembolism and to treat them accordingly.

[Trauma-induced coagulopathy--mechanisms and state of the art treatment].

PubMed

Misgav, Mudi; Martinowitz, Uri

2011-02-01

Uncontrolled bleeding is a major cause for early death in both military and civilian trauma. The process of massive bleeding which begins as "surgical bleed" from injured vessels may rapidly evolve into a complex coagulopathy that can be detected early, sometimes within minutes of injury. The magnitude of coagulopathy is directly related to the severity of the injury and its presence is also an independent predictor of early mortality. Therefore, an early "hemostatic resuscitation" is now the "state of the art" in trauma management. Combined mechanisms contribute to the complex coagulopathy as described herein: excessive consumption of coagulation factors and platelets, dilutional coagulopathy due to administration of large volumes of fluids, especially high molecular solutions such as Hydroxyethyl starch (HES); the use of multiple red blood cells (RBC) transfusion without sufficient fresh frozen plasma (FFP) and platelets; acidosis that markedly attenuates thrombin generation and platelets function; hypothermia that slows down enzymatic reactions and platelets function and hyperfibrinolysis which accelerates the degradation of fibrin and might cause platelet dysfunction. An important breakthrough was the understanding that abnormal coagulation tests early in the process of trauma are not the consequences of disseminated intravascular coagulation (DIC). Supported by these new data, an aggressive approach to hemostatic resuscitation was developed which is based on the following principles: permissive hypotension to avoid "dilutional" coagulopathy, awareness of the prevention of hypothermia and acidosis and the use of hemostatic agents such as rFVIIa, fibrinogen concentrate and tranexamic acid early in the course of trauma. Importantly, the common practice of blood component therapy was revised and it is recommended that RBC, FFP and platelets will be transfused early and preferably in 1:1:1 ratio.

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

PubMed Central

Beer, Sandra; Feihl, François; Ruiz, Juan; Juhan-Vague, Irène; Aillaud, Marie-Françoise; Wetzel, Sandrine Golay; Liaudet, Lucas; Gaillard, Rolf C; Waeber, Bernard

2008-01-01

Aim: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. Methods: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. Results: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. Conclusion: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state. PMID:19337558

[Modified polyurethane foam as a local hemostatic agent after dental extractions].

PubMed

Selten, M H A; Broekema, F I; Zuidema, J; van Oeveren, W; Bos, R R M

2013-01-01

In this split mouth experiment, the feasibility ofpolyurethane foam as a local hemostatic agent after dental extractions was studied. Ten healthy patients underwent 2 extractions ofa dental element in 1 treatment session. The 10 patients were subsequently randomly divided in a gelatin group and a collagen group. In the gelatin group, a polyurethane foam (PU) was applied in 1 extraction socket, while in the other socket a commercially available gelatin foam was applied. In the collagen group, a PU was applied in 1 socket, and a collagen wadding in the other. All hemostats were removed after 2 minutes, after which the degree of coagulation was measured using a thrombin/antithrombin test and a fibrinogen test. This study suggests that polyurethane foam has hemostatic capacity. Large scale clinical research is needed to confirm this finding, and should indicate whether this hemostatic capacity is clinically relevant.

Overview of the Hemostasis Research Program: Advances and Future Directions

DTIC Science & Technology

2004-09-01

Gauze sponges - Clamps ◆ Noncompressible - Intracavitary hemostatic agent - High Intensity Focused Ultrasound ( HIFU ) - Drugs to enhance hemostatic...7 2.6 High Intensity Focused Ultrasound ( HIFU ) Device In addition to screening potential hemostatic agents, the ISR is currently evaluating...Drugs to Treat Coagulopathy High Intensity Focused Ultrasound Self/Buddy Aid Battalion Surgeon Scenario One: Bullet Wound to Thigh (Femoral

Effect of iodinated low-osmolar contrast media on the hemostatic system after intraarterial and intravenous contrast administration.

PubMed

Lukasiewicz, A; Lebkowska, U; Galar, M

2012-01-01

Some of the adverse clinical effects of intravascular radiological contrast agents include the interference of these contrast media with normal hemostatic processes. The aim of this report was to investigate in vivo whether a non-ionic iodinated contrast agent possess prothrombotic or anticoagulant properties. Hemostatic parameters: vWF (von Willebrand factor), F1+2 (prothrombin fragments 1+2), TAT (thrombin-antithrombin complexes), D-Dimer, β-TG (beta-thromboglobulin) were measured in a group of 35 patients. Blood samples for laboratory investigations were collected before and 30 min after the administration of a iodine contrast agent. There was observed statistically highly significant contrast-induced increase in TAT and F1+2 (p = 0.005 and p = 0.008, respectively). D-Dimer increase and decrease of β-TG and vWF after contrast medium administration were non significant. The volume of contrast medium has no influence on the assessed hemostatic parameters, while the type of contrast medium and/or the route of the contrast administration may significantly affect hemostatic parameters. We found significant effects of non-ionic agents on hemostatic activation. These effects may be important for adverse reactions and for thromboembolic complications.

Ankaferd hemostat in the management of gastrointestinal hemorrhages

PubMed Central

Beyazit, Yavuz; Kekilli, Murat; Haznedaroglu, Ibrahim C; Kayacetin, Ertugrul; Basaranoglu, Metin

2011-01-01

Gastrointestinal (GI) bleeding refers to any hemorrhage ascribed to the pathologies of the gastrointestinal tract, extending from the mouth to the anal canal. Despite the recent improvements in the endoscopic, hemostatic and adjuvant pharmacologic techniques, the reported mortality is still around 5%-10% for peptic ulcer bleeding and about 15%-20% for variceal hemorrhages. Although endoscopic management reduces the rates of re-bleeding, surgery, and mortality in active bleeding; early recurrence ratios still occur in around 20% of the cases even with effective initial hemostatic measures. In this quest for an alternative pro-hemostatic agent for the management of GI bleedings, Ankaferd blood stopper (ABS) offers a successful candidate, specifically for “difficult-to-manage” situations as evidenced by data presented in several studies. ABS is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. It is effective in both bleeding individuals with normal hemostatic parameters and in patients with deficient primary and/or secondary hemostasis. ABS also modulates the cellular apoptotic responses to hemorrhagic stress, as well as hemostatic hemodynamic activity. Through its effects on the endothelium, blood cells, angiogenesis, cellular proliferation, vascular dynamics, and wound healing, ABS is now becoming an effective alternative hemostatic medicine for gastrointestinal bleedings that are resistant to conventional anti-hemorrhagic measurements. The aim of this review is to outline current literature experience suggesting the place of ABS in the management of GI bleeding, and potential future controlled trials in this complicated field. PMID:22046083

Marginal integrity of low-shrinkage and methacrylate-based composite resins: Effect of three different hemostatic agents

PubMed Central

Khoroushi, Maryam; Sahraneshin-Samani, Mahsa

2016-01-01

Background Moisture control is very important in restorative procedures in dentistry. Use of hemostatic agents helps control moisture; however, they might result in changes on enamel and dentin surfaces, affecting composite resin bond quality. The aim of this in vitro study was to evaluate the marginal microleakage of two different composite resins with the use of three different hemostatic agents. Material and Methods Standardized Class V cavities were prepared on the buccal and lingual surfaces of 48 premolars with cervical margins 1 mm apical to the cementoenamel junction (CEJ). The samples were randomly divided into 8 groups. In groups 1 to 4, an etch-and-rinse adhesive (Adper Single Bond) was applied as the bonding system, followed by exposure to different hemostatic agent: group 1: no hemostatic agent (control); group 2: ViscoStat; group 3: ViscoStat Clear; and group 4: trichloracetic acid, as hemostatic agents. The cavities were restored with Z-250 composite resin. In group 5 to 8 Silorane System Adhesive (Filtek P90 Adhesive) was applied as a bonding agent, followed by exposure to different hemostatic agents in a manner similar to that in groups 1to 4. The cavities were restored with Filtek P90, a low-shrinkage composite resin. The samples in each group were evaluated for dye penetration under a stereomicroscope at ×36 after 24 hours and a 500-round thermocycling procedure at enamel and dentin margins. Statistical analysis was carried out using Kruskal-Wallis and Mann-Whitney tests (α=0.05). Results Z-250 composite resin exhibited significantly higher dentin microleakage scores compared to Filtek P90 (P = 0.004). Trichloracetic acid increased dentin microleakage with Filtek P90 (P=0.033). Conclusions Under the limitations of this in vitro study, application of hemostatic agents did not affect microleakage of the two tested composite resins except for trichloracetic acid that increased marginal microleakage when used with Filtek P90. Key words:Composite resin, dental leakage, hemostatics, silorane system adhesive. PMID:27034759

Hemostasis in a noncompressible hemorrhage model: an end-user evaluation of hemostatic agents in a proximal arterial injury.

PubMed

Satterly, Steven; Nelson, Daniel; Zwintscher, Nathan; Oguntoye, Morohunranti; Causey, Wayne; Theis, Bryan; Huang, Raywin; Haque, Mohamad; Martin, Matthew; Bickett, Gerald; Rush, Robert M

2013-01-01

1. Evaluate hemostatic bandages by the end user using subjective and objective criteria. 2. Determine if user training and education level impact overall hemostatic outcomes. 3. Our hypothesis was that prior medical training would be directly linked to improved hemostatic outcomes in noncompressible hemorrhage indepen- dent of dressing used. Military personnel were given standardized instruction on hemostatic dressings as part of a tactical combat casualty care course (TC3). Soldiers were randomized to a hemostatic dressing. Proximal arterial (femoral and axillary) injuries were created in extremities of live tissue models (goat or pig). Participants attempted hemostasis through standardized dressing application. Evaluation of hemostasis was performed at 2- and 4-minute intervals by physicians blinded to participants' training level. Military personnel that are due to deploy are given "refresher" instruction by their units as well as participating in the TC3 to further hone their medical skills prior to deployment. The TC3 is simulation training designed to simulate combat environments and real-life trauma scenarios. Military personnel due to deploy, physicians (residents and board certified surgeons), animal care technicians, and veterinarian support. Celox 42 (33%), ChitoGauze 11 (9%), Combat Gauze 45 (35%), and HemCon wafer 28 (22%) bandages were applied in 126 arterial injuries created in 45 animals in a standardized model of hemorrhage. Overall, no significant difference in hemostasis and volume of blood loss was seen between the 4 dressings at 2 or 4 minutes. Combat gauze was the most effective at controlling hemorrhage, achieving 83% hemostasis by 4 minutes. Combat gauze was also rated as the easiest dressing to use by the soldiers (p<0.05). When compared to nonmedical personnel, active duty soldiers with prior medical training improved hemostasis at 4 minutes by 20% (p = 0.05). There is no significant difference in hemostasis between hemostatic bandages for proximal arterial hemorrhage. Hemostasis significantly improves between 2 and 4 minutes using direct pressure and hemostatic agents. Prior medical training leads to 20% greater efficacy when using hemostatic dressings. Published by Elsevier Inc.

Synthetic Strategies for Engineering Intravenous Hemostats

PubMed Central

Chan, Leslie W.-G.; White, Nathan J.; Pun, Suzie H.

2015-01-01

While there are currently many well-established topical hemostatic agents for field administration, there are still limited tools to staunch bleeding at less accessible injury sites. Current clinical methods of restoring hemostasis after large volume blood loss include platelet and clotting factor transfusion, which have respective drawbacks of short shelf-life and risk of viral transmission. Therefore, synthetic hemostatic agents that can be delivered intravenously and encourage stable clot formation after localizing to sites of vascular injury are particularly appealing. In the past three decades, platelet substitutes have been prepared using drug delivery vehicles such as liposomes and PLGA nanoparticles that have been modified to mimic platelet properties. Additionally, structural considerations such as particle size, shape, and flexibility have been addressed in a number of reports. Since platelets are the first responders after vascular injury, platelet substitutes represent an important class of intravenous hemostats under development. More recently, materials affecting fibrin formation have been introduced to induce faster or more stable blood clot formation through fibrin crosslinking. Fibrin represents a major structural component in the final blood clot, and a fibrin-based hemostatic mechanism acting downstream of initial platelet plug formation may be a safer alternative to platelets to avoid undesired thrombotic activity. This review explores intravenous hemostats under development and strategies to optimize their clotting activity. PMID:25803791

Comparative evaluation of absorbable hemostats: advantages of fibrin-based sheets.

PubMed

Krishnan, Lissy K; Mohanty, Mira; Umashankar, P R; Lal, Arthur Vijayan

2004-11-01

Bioactive hemostats and wound dressings consist of either inherently active materials or act as delivery vehicles which contain such materials. Fibrin is a natural hemostat and scaffold, guiding the direction of wound contraction and closure. In order to improve the ease of application of liquid fibrin glue, we have made a freeze-dried form of polymerized fibrin that supports hemostasis and wound healing. The bleeding from the middle ear artery of rabbits was found to be arrested instantaneously on application of fibrin sheets, even when the animal was heparinized systemically. As the fibrin sheet was found to be fragile, gelatin was incorporated to the sheet and thus the mechanical stability was improved without compromising the hemostatic effect. The efficacy of the fabricated fibrin and fibrin-gelatin sheets to seal traumatized rat liver was compared with commercially available hemostats, Abgel (cross-linked gelatin) and Surgicel (cross-linked cellulose). Tissue compatibility of all the hemostats was studied by analyzing the liver tissue 15 days after application. While the hemostatic effect was best with fibrin and fibrin-gelatin sheets, both Surgicel and Abgel were not capable of arresting the bleeding quickly. Gross analysis of tissue on the 15th day of application, visibly, Abgel was not only degraded but resulted in severe adhesions of internal organs and histologically capsule formation around the implant was evident. Though Surgicel was also seen as cream soft material on the site of application that joined two pieces of liver, there was no adhesion of other internal organs and histologically, immune reaction and foreign-body-type giant cells were present in large amounts. Fibrin was not found grossly on application site whereas fibrin-gelatin was seen as a small white spot. Granulation tissue formation and cell migration into the fibrin-based sheets were evident, and therefore, fibrin-based sheets are not only efficient hemostats but showed optimum degradation and wound healing.

Embolization with ethylene vinyl alcohol copolymer (Onyx®) for peripheral hemostatic and non-hemostatic applications: a feasibility and safety study

PubMed Central

Né, Romaric; Chevallier, Olivier; Falvo, Nicolas; Facy, Olivier; Berthod, Pierre-Emmanuel; Galland, Christophe; Gehin, Sophie; Midulla, Marco

2018-01-01

Background Onyx® is a liquid embolic agent, which is approved for the treatment of cerebral vascular lesions but still rarely used in peripheral interventional radiology. The goal of this study is to report the feasibility and safety of embolization with Onyx® for peripheral hemostatic and non-hemostatic endovascular procedures. Methods Retrospective study of all consecutive patients who underwent visceral or peripheral embolization with Onyx® for hemostatic or non-hemostatic purpose in our department between May 2014 and November 2016. Demographic data, clinical presentation, underlying etiology, culprit vessel, endovascular procedure, pain during embolization, outcomes, and follow-up data were collected. Results Fifty patients (males, 34; females, 16; mean age, 56±18 years; range, 15–89 years) were included. Twenty-nine (58%) of patients underwent hemostatic embolization for arterial (n=22, 44%) or venous (n=7, 14%) bleeding lesions, whereas 21 (42%) of patients underwent non-hemostatic embolization for arterial aneurysms (n=8, 16%), preoperative portal vein deprivation (n=6, 12%) or other indications (n=7, 14%). Onyx-18 was used in 37 (74%) patients, Onyx-34 in 9 (18%) patients, and a combination of both in 4 (8%) patients. Onyx was used alone in 25 (50%) patients and in combination with other agent in 25 (50%) patients. Mean number of Onyx® vials used was 3.7 (range, 1–17). Immediate technical success rate was 100%. Primary clinical success was achieved in all patients. Recurrent bleeding occurred in two patients. Significant pain (pain score ≥3) was noted during injection in 10 (20%) patients. No major complication or side effects were noted within 1 month. Conclusions Transcatheter embolization with Onyx® is feasible and safe in the peripheral arterial or venous vasculature for both bleeding and non-bleeding patients whatever the anatomic site. PMID:29774181

Embolization with ethylene vinyl alcohol copolymer (Onyx®) for peripheral hemostatic and non-hemostatic applications: a feasibility and safety study.

PubMed

Né, Romaric; Chevallier, Olivier; Falvo, Nicolas; Facy, Olivier; Berthod, Pierre-Emmanuel; Galland, Christophe; Gehin, Sophie; Midulla, Marco; Loffroy, Romaric

2018-04-01

Onyx ® is a liquid embolic agent, which is approved for the treatment of cerebral vascular lesions but still rarely used in peripheral interventional radiology. The goal of this study is to report the feasibility and safety of embolization with Onyx ® for peripheral hemostatic and non-hemostatic endovascular procedures. Retrospective study of all consecutive patients who underwent visceral or peripheral embolization with Onyx ® for hemostatic or non-hemostatic purpose in our department between May 2014 and November 2016. Demographic data, clinical presentation, underlying etiology, culprit vessel, endovascular procedure, pain during embolization, outcomes, and follow-up data were collected. Fifty patients (males, 34; females, 16; mean age, 56±18 years; range, 15-89 years) were included. Twenty-nine (58%) of patients underwent hemostatic embolization for arterial (n=22, 44%) or venous (n=7, 14%) bleeding lesions, whereas 21 (42%) of patients underwent non-hemostatic embolization for arterial aneurysms (n=8, 16%), preoperative portal vein deprivation (n=6, 12%) or other indications (n=7, 14%). Onyx-18 was used in 37 (74%) patients, Onyx-34 in 9 (18%) patients, and a combination of both in 4 (8%) patients. Onyx was used alone in 25 (50%) patients and in combination with other agent in 25 (50%) patients. Mean number of Onyx ® vials used was 3.7 (range, 1-17). Immediate technical success rate was 100%. Primary clinical success was achieved in all patients. Recurrent bleeding occurred in two patients. Significant pain (pain score ≥3) was noted during injection in 10 (20%) patients. No major complication or side effects were noted within 1 month. Transcatheter embolization with Onyx ® is feasible and safe in the peripheral arterial or venous vasculature for both bleeding and non-bleeding patients whatever the anatomic site.

Efficacy, Reliability, and Safety of Completely Autologous Fibrin Glue in Neurosurgical Procedures: Single-Center Retrospective Large-Number Case Study.

PubMed

Nakayama, Noriyuki; Yano, Hirohito; Egashira, Yusuke; Enomoto, Yukiko; Ohe, Naoyuki; Kanemura, Nobuhiro; Kitagawa, Junichi; Iwama, Toru

2018-01-01

Commercially available fibrin glue (Com-FG), which is used commonly worldwide, is produced with pooled human plasma from multiple donors. However, it has added bovine aprotinin, which involves the risk of infection, allogenic immunity, and allergic reactions. We evaluate the efficacy, reliability, and safety of completely autologous fibrin glue (CAFG). From August 2014 to February 2016, prospective data were collected and analyzed from 153 patients. CAFG was prepared with the CryoSeal System using autologous blood and was applied during neurosurgical procedures. Using CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets, we performed a pinpoint hemostasis, transposed the offending vessels in a microvascular decompression, and covered the dural incision to prevent cerebrospinal fluid leakage. The CryoSeal System had generated up to a mean of 4.51 mL (range, 3.0-8.4 mL) of CAFG from 400 mL autologous blood. Com-FG products were not used in our procedures. Only 6 patients required an additional allogeneic blood transfusion. The hemostatic effective rate was 96.1% (147 of 153 patients). Only 1 patient who received transsphenoidal surgery for a pituitary adenoma presented with the complication of delayed postoperative cerebrospinal fluid leakage (0.65%). No patient developed allergic reactions or systemic complications associated with the use of CAFG. CAFG effectively provides hemostatic, adhesive, and safety performance. The timing and three-dimensional shape of CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets solidification can be controlled with slow fibrin formation. The cost to prepare CAFG is similar compared with Com-FG products, and it can therefore be easily used at most institutions. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of aluminum chloride hemostatic agent on microleakage of class V composite resin restorations bonded with all-in-one adhesive

PubMed Central

Mohammadi, Narmin; Bahari, Mahmood; Pournaghi-Azar, Fatemeh; Mozafari, Aysan

2012-01-01

Objectives: Since hemostatic agents can induce changes on enamel and dentin surfaces and influence composite resin adhesion, the aim of the present study was to evaluate the effect of the aluminum chloride hemostatic agent on the gingival margin microleakage of class V (Cl V) composite resin restorations bonded with all-in-one adhesive. Study design: Cl V cavities were prepared on the buccal surfaces of 60 sound bovine permanent incisors. Gingival margins of the cavities were placed 1.5 mm apical to the cemento-enamel junction (CEJ). The teeth were randomly divided into two groups of 30. In group 1, the cavities were restored without the application of a hemostatic agent; in group 2, the cavities were restored after the application of the hemostatic agent. In both groups all-in-one adhesive and Z250 composite resin were used to restore the cavities with the incremental technique. After finishing and polishing, the samples underwent a thermocycling procedure, followed by immersion in 2% basic fuschin solution for 24 hours. The samples were sectioned and gingival microleakage was evaluated under a stereomicroscope. The non-parametric Mann-Whitney U test was used to compare microleakage between the two groups. Statistical significance was defined at P<0.05. Results: A statistically significant difference was observed in microleakage between the two groups (P<0.001). Conclusions: Contamination of Cl V composite resin restorations bonded with all-in-one adhesive with aluminum chloride hemostatic agent significantly increases restoration gingival margin microleakage. Key words:All-in-one adhesive resin, composite resin restoration, hemostatic agent, microleakage. PMID:22322497

The effects of hemostatic agents on peripheral nerve function: an experimental study.

PubMed

Alkan, Alper; Inal, Samet; Yildirim, Mehmet; Baş, Burcu; Ağar, Erdal

2007-04-01

In the practice of oral and maxillofacial surgery, hemostatic agents are sometimes placed in close proximity to peripheral nerves. In the present study, we evaluated immediate and delayed effects of 4 hemostatic agents (oxidized regenerated cellulose, 5% colloid silver-added gelatine sponge, bovine collagen, bone wax) on peripheral nerve function. A total of 25 rat sciatic nerves were prepared, and the amplitudes were recorded with a physiological data acquisition system. Animals were randomly assigned to 5 groups: control, oxidized regenerated cellulose, gelatine sponge, bone wax, and bovine collagen. The first hour records are defined as immediate effects of these hemostatic agents on nerve function. The animals were then allowed to recover for 4 weeks. At the end of this period, the same surgical and recording procedures were performed. These final records are defined as delayed effects of hemostatic agents on nerve function. According to nerve conduction velocity (NCV) and compound action potential (CAP) values of the experimental groups, early and delayed effects of each hemostatic agent were statistically compared with Bonferroni corrected test (P < .05). Statistically, NCV was significantly reduced, and the CAP was significantly increased 1 hour after surgery (P < .05) in the group of oxidized regenerated cellulose. However, there were no significant differences after 4 weeks compared with the first records. In the gelatine sponge group, CAP was significantly increased 4 weeks after the application. In the bovine collagen and bone wax groups, NCV and CAP values (1 hour and 4 weeks after the application) were not statistically significant compared with initial control records. The present study shows that bovine collagen is the most suitable hemostatic agent applicable for peripheral nerves.

Usefulness of hemostatic sealants for minimizing ovarian damage during laparoscopic cystectomy for endometriosis.

PubMed

Choi, Chahien; Kim, Woo Young; Lee, Dong Hee; Lee, San Hui

2018-03-01

We aimed to evaluate the impact of topical hemostatic sealants and bipolar coagulation during laparoscopic ovarian endometriotic cyst resection on ovarian reserve by comparing the rates of decrease in anti-Müllerian hormone (AMH). A randomized prospective data collection was made on women aged 19-45 years who planned to have laparoscopic ovarian cystectomy at one of two institutions (n = 80), Kangbuk Samsung Hospital, Seoul, Korea or National Health Insurance Service Ilsan Hospital, Goyang, Korea, from January 2014 to April 2016. Patients were randomly divided into two groups treated with either a topical hemostatic sealant or bipolar coagulation for hemostasis. The hemostatic group was randomized to the FloSeal or TachoSil subgroups. Preoperative and 3-month postoperative AMH levels were checked and the rates of decrease of AMH were compared. All patients enrolled were treated with dienogest (Visanne) for 6-12 months. None were lost to follow-up at postoperative 3 months, but about one-third of the patients had been lost to follow-up by 6-12 months. AMH was significantly decreased in both groups 3 months postoperatively; however, the rate of decrease in the bipolar coagulation group was greater than that in the hemostatic sealant group, 41.9% (interquartile range [IQR], 22.29-65.24) versus 18.1% (IQR, 10.94-29.90), P = 0.007. Between the two hemostatic subgroups, there was no significant difference in AMH decrease rate, 14.95% (IQR, 11.34-21.21) versus 18.1% (IQR 9.76-40.70), P = 0.204. Hemostatic sealants may be an alternative to bipolar coagulation for preservation of ovarian reserve after laparoscopic ovarian cystectomy for endometriosis. © 2017 Japan Society of Obstetrics and Gynecology.

Comparison of sea turtle thrombocyte aggregation to human platelet aggregation in whole blood.

PubMed

Soslau, Gerald; Prest, Phillip J; Class, Reiner; George, Robert; Paladino, Frank; Violetta, Gary

2005-11-01

The endangered sea turtles are living "fossils" that afford us an opportunity to study the hemostatic process as it likely existed millions of years ago. There are essentially no data about turtle thrombocyte aggregation prior to our studies. Thrombocytes are nucleated cells that serve the same hemostatic functions as the anucleated mammalian platelet. Sea turtle thrombocytes aggregate in response to collagen and beta-thrombin. Ristocetin induces an agglutination/aggregation response indicating the presence of a von Willebrand-like receptor, GPIb, found in all mammalian platelets. Samples treated with alpha-thrombin plus gamma-thrombin followed by ristocetin results in a rapid, stronger response than ristocetin alone. These responses are inhibited by the RGDS peptide that blocks fibrinogen cross-linking of mammalian platelets via the fibrinogen receptor, GPIIb/IIIa. Three platelet-like proteins, GPIb, GPIIb/IIIa and P-selection are detected in sea turtle thrombocytes by fluorescence activated cell sorting. Turtle thrombocytes do not respond to ADP, epinephrine, serotonin, thromboxane A2 mimetic, U46619, trypsin, or alpha-thrombin and gamma-thrombin added alone. Comparison of hemostasis in sea turtles to other vertebrates could provide a framework for understanding the structure/function and evolution of these pathways and their individual components.

Hemostatic granules and dressing prepared from formulations of carboxymethyl cellulose, kappa-carrageenan and polyethylene oxide crosslinked by gamma radiation

NASA Astrophysics Data System (ADS)

Barba, Bin Jeremiah D.; Aranilla, Charito T.; Relleve, Lorna S.; Cruz, Veriza Rita C.; Vista, Jeanina Richelle; Abad, Lucille V.

2018-03-01

Uncontrolled hemorrhage remains a persistent problem especially in anatomical areas where compression and tourniquet cannot be applied. Hemostatic agents are materials which can achieve control of bleeding in acute, life-threatening traumatic coagulopathy. In this study, we prepared biocompatible hydrogel-based hemostat crosslinked by ionizing radiation. Granules made from carboxymethyl cellulose and dressing from kappa carrageenan and polyethylene oxide were characterized by FT-IR, SEM, and gel analysis. Gamma radiation with a dose of 25 kGy was used for sterilization process. Stability studies indicate that the products remain effective with a shelf life of up to 18 months based on accelerated aging. Both hemostatic agents were demonstrated to be effective in vitro blood clotting assays showing a low blood clotting index, high platelet adhesion capacity and accelerated clotting time. Hemostat granules and dressing were also used in a femoral artery rat bleeding model where hemorrhage control was achieved in 90 s without compression and resulted in 100% survival rate after a 7 and 14-day observation.

Damage Control for Vascular Trauma from the Prehospital to the Operating Room Setting.

PubMed

Pikoulis, Emmanouil; Salem, Karim M; Avgerinos, Efthymios D; Pikouli, Anastasia; Angelou, Anastasios; Pikoulis, Antreas; Georgopoulos, Sotirios; Karavokyros, Ioannis

2017-01-01

Early management of vascular injury, starting at the field, is imperative for survival no less than any operative maneuver. Contemporary prehospital management of vascular trauma, including appropriate fluid and volume infusion, tourniquets, and hemostatic agents, has reversed the historically known limb hemorrhage as a leading cause of death. In this context, damage control (DC) surgery has evolved to DC resuscitation (DCR) as an overarching concept that draws together preoperative and operative interventions aiming at rapidly reducing bleeding from vascular disruption, optimizing oxygenation, and clinical outcomes. This review addresses contemporary DCR techniques from the prehospital to the surgical setting, focusing on civilian vascular injuries.

Mechanistic investigation of a hemostatic keratin biomaterial

NASA Astrophysics Data System (ADS)

Rahmany, Maria Bahawdory

Traumatic injury leads to more productive years lost than heart disease, cancer and stroke combined. Trauma is often accompanied and complicated by uncontrolled bleeding. Human hair keratin biomaterials have demonstrated efficacy in controlling hemorrhage in both small and large animal models; however little is known about the mechanism by which these proteins aid in blood clotting. Inspection of the amino acid sequence of known keratins shows the presence of several cellular binding motifs, suggesting a possible mechanism and potentially eliminating the need to functionalize the material's surface for cellular interaction. In addition to small animal studies, the hemostatic activity of keratin hydrogels was explored through porcine hemorrhage models representing both a high flow and low flow bleed. In both studies, keratin hydrogels appeared to lead to a significant reduction in blood loss. The promising results from these in vivo studies provided the motivation for this project. The objective of this dissertation work was to assess the mechanism of action of a hemostatic keratin biomaterial, and more broadly assess the biomaterial-cellular interaction(s). It is our hypothesis that keratin biomaterials have the capacity to specifically interact with cells and lead to propagation of intracellular signaling pathway, specifically contributing to hemostasis. Through application of biochemical and molecular tools, we demonstrate here that keratin biomaterials contribute to hemostasis through two probable mechanisms; integrin mediated platelet adhesion and increased fibrin polymerization. Platelets are the major cell type involved in coagulation both by acting as a catalytic surface for the clotting cascade and adhering to extracellular matrix (ECM) proteins providing a soft platelet plug. Because keratin biomaterials have structural and biochemical characteristics similar to ECM proteins, we utilized several adhesion assays to investigate platelet adhesion to keratin biomaterial surfaces. While other groups have discussed keratin's capacity to specifically adhere cells, this work was the first to utilize function blocking antibodies to deduce the specific receptors involved in mediating the cell-keratin interaction. To explore keratin's role in the second arm of coagulation, the clotting cascade, we followed the kinetic behavior of fibrin generation in the presence and absence of keratin. Confirmed with samples of plasma and a purified system of fibrinogen and thrombin, we observed an increased rate of fibrin polymerization in the presence of keratin proteins. The final goal of this project was to utilize a Chinese hamster ovary cell line to more specifically explore integrin-mediated cell interactions with keratin biomaterials in a controlled, biologically relevant system. Together, this work provides key details regarding keratin's hemostatic characteristics, providing the foundations for further development and optimizing of the material's unique characteristics for use as a hemostatic agent. More broadly, application of the CHO cell model could provide a useful tool for developing a receptor-ligand profile for keratin biomaterials.

Effect of carprofen on hemostatic variables in dogs.

PubMed

Hickford, F H; Barr, S C; Erb, H N

2001-10-01

To evaluate the effect of carprofen on hemostatic variables in clinically normal dogs. 12 clinically normal Labrador Retrievers. 10 dogs (6 females, 4 males) received carprofen (2.2 mg/kg of body weight, PO, q 12 h) for 5 days. Two dogs (untreated control group; 1 female, 1 male) did not receive carprofen. Hemostatic variables (platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, platelet aggregation, and bleeding time) were assessed for all dogs prior to treatment, on day 5 of treatment, and 2 and 7 days after discontinuation of the drug (days 7 and 12). Serum biochemical variables and Hct were assessed prior to treatment and on days 5 and 12. In dogs receiving carprofen, platelet aggregation was significantly decreased, and onset of aggregation was significantly delayed on days 5, 7, and 12, compared with pretreatment values. Activated partial thromboplastin time was significantly increased on days 5, 7, and 12 over pretreatment values in treated dogs, but values remained within reference ranges. Significant differences were not detected in buccal mucosal bleeding time, other serum biochemical and hemostatic variables, or Hct, compared with pretreatment values and the internal control group. Administration of carprofen for 5 days causes minor but not clinically important alterations in hemostatic and serum biochemical variables in clinically normal Labrador Retrievers. Carprofen is commonly used to treat osteoarthritis and chronic pain in dogs, but prior to this study, its effect on platelet aggregation and hemostatic variables was unknown.

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

PubMed Central

2012-01-01

Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130 PMID:23137020

[Bed-side management of post-operative bleeding in transurethral resection of the prostate--hemostatic trial with thrombin solution injected into the resected cavity of the prostate].

PubMed

Hasegawa, S; Nakashima, J; Kimura, S

1987-08-01

To control post-operative bleeding from the resected cavity in transurethral resection of the prostate (TUR-P), 20,000 units of thrombin dissolved in 5-20 ml of physiological saline was injected into the cavity in one shot with a new type of 3-way Foley catheter. The catheter has two holes close to the balloon, and the holes provide outlets through which the solution is directly injected into the cavity. Out of 23 patients between 58 and 87 years old, 11 were given thrombin and 12 were control cases. In each case, urine blood volume (ml/hr) was determined before (a) and after (b) injection. The hemostatic effect was assessed with a "hemostatic index" of b/a. There was a statistically significant difference in the hemostatic indices between thrombin group and the control. (p less than 0.02) This new hemostatic method proved to be a very useful easy bed-side technique to control bleeding even in sudden bleeding after TUR-P. No serious side effects were found during the course of this study.

Graphene-Montmorillonite Composite Sponge for Safe and Effective Hemostasis.

PubMed

Li, Guofeng; Quan, Kecheng; Liang, Yuping; Li, Tianyi; Yuan, Qipeng; Tao, Lei; Xie, Qian; Wang, Xing

2016-12-28

Montmorillonite (MMT) is considered to be the most effective hemostat among natural phyllosilicates. However, there is a barrier against using MMT for the commercial hemostatics because the invaded MMT powders might cause thrombosis in vessel. Until now, it is still a challenge to manage the release of MMT and eliminate its side effect. Herein, we present a graphene-MMT composite sponge (GMCS), synthesized under a hydrothermal reaction, fixing MMT powders into the cross-linked graphene sheets. We demonstrate that only a few embedded MMT can evoke remarkable platelet stimulation at the sponge interface, while maintaining fast plasma absorbency of the innate sponge. In the synergy of the above hemostatic mechanisms, the GMCS can rapidly stop bleeding in approximately 85 s in rabbit artery injury test. More importantly, computed tomography angiography certifies that the GMCS does not cause thrombus or blood clot in vessels. Cytotoxicity assay further highlights its biocompatibility. In-depth analysis proposes that two-dimensional graphene overmatches one-dimensional linear polymers in the composite construction, and dimension transformation of blood distribution plays a crucial role for reinforcing the hemostatic performance. This GMCS hemostat not only opens a new perspective for graphene composite, but also makes a new chance of using clays for trauma therapy.

Hemostatic powder spray: a new method for managing gastrointestinal bleeding

PubMed Central

Papafragkakis, Haris; Ofori, Emmanuel; Ona, Mel A.; Krishnaiah, Mahesh; Duddempudi, Sushil; Anand, Sury

2015-01-01

Gastrointestinal bleeding is a leading cause of morbidity and mortality in the United States. The management of gastrointestinal bleeding is often challenging, depending on its location and severity. To date, widely accepted hemostatic treatment options include injection of epinephrine and tissue adhesives such as cyanoacrylate, ablative therapy with contact modalities such as thermal coagulation with heater probe and bipolar hemostatic forceps, noncontact modalities such as photodynamic therapy and argon plasma coagulation, and mechanical hemostasis with band ligation, endoscopic hemoclips, and over-the-scope clips. These approaches, albeit effective in achieving hemostasis, are associated with a 5–10% rebleeding risk. New simple, effective, universal, and safe methods are needed to address some of the challenges posed by the current endoscopic hemostatic techniques. The use of a novel hemostatic powder spray appears to be effective and safe in controlling upper and lower gastrointestinal bleeding. Although initial reports of hemostatic powder spray as an innovative approach to manage gastrointestinal bleeding are promising, further studies are needed to support and confirm its efficacy and safety. The aim of this study was to evaluate the technical feasibility, clinical efficacy, and safety of hemostatic powder spray (Hemospray, Cook Medical, Winston-Salem, North Carolina, USA) as a new method for managing gastrointestinal bleeding. In this review article, we performed an extensive literature search summarizing case reports and case series of Hemospray for the management of gastrointestinal bleeding. Indications, features, technique, deployment, success rate, complications, and limitations are discussed. The combined technical and clinical success rate of Hemospray was 88.5% (207/234) among the human subjects and 81.8% (9/11) among the porcine models studied. Rebleeding occurred within 72 hours post-treatment in 38 patients (38/234; 16.2%) and in three porcine models (3/11; 27.3%). No procedure-related adverse events were associated with the use of Hemospray. Hemospray appears to be a safe and effective approach in the management of gastrointestinal bleeding. PMID:26082803

Hemostatic powder spray: a new method for managing gastrointestinal bleeding.

PubMed

Changela, Kinesh; Papafragkakis, Haris; Ofori, Emmanuel; Ona, Mel A; Krishnaiah, Mahesh; Duddempudi, Sushil; Anand, Sury

2015-05-01

Gastrointestinal bleeding is a leading cause of morbidity and mortality in the United States. The management of gastrointestinal bleeding is often challenging, depending on its location and severity. To date, widely accepted hemostatic treatment options include injection of epinephrine and tissue adhesives such as cyanoacrylate, ablative therapy with contact modalities such as thermal coagulation with heater probe and bipolar hemostatic forceps, noncontact modalities such as photodynamic therapy and argon plasma coagulation, and mechanical hemostasis with band ligation, endoscopic hemoclips, and over-the-scope clips. These approaches, albeit effective in achieving hemostasis, are associated with a 5-10% rebleeding risk. New simple, effective, universal, and safe methods are needed to address some of the challenges posed by the current endoscopic hemostatic techniques. The use of a novel hemostatic powder spray appears to be effective and safe in controlling upper and lower gastrointestinal bleeding. Although initial reports of hemostatic powder spray as an innovative approach to manage gastrointestinal bleeding are promising, further studies are needed to support and confirm its efficacy and safety. The aim of this study was to evaluate the technical feasibility, clinical efficacy, and safety of hemostatic powder spray (Hemospray, Cook Medical, Winston-Salem, North Carolina, USA) as a new method for managing gastrointestinal bleeding. In this review article, we performed an extensive literature search summarizing case reports and case series of Hemospray for the management of gastrointestinal bleeding. Indications, features, technique, deployment, success rate, complications, and limitations are discussed. The combined technical and clinical success rate of Hemospray was 88.5% (207/234) among the human subjects and 81.8% (9/11) among the porcine models studied. Rebleeding occurred within 72 hours post-treatment in 38 patients (38/234; 16.2%) and in three porcine models (3/11; 27.3%). No procedure-related adverse events were associated with the use of Hemospray. Hemospray appears to be a safe and effective approach in the management of gastrointestinal bleeding.

Use of a contoured bioresorbable plate with a hemostatic plug to control life-threatening bleeding from the superior sagittal sinus during hemispherotomy: technical note.

PubMed

Tuite, Gerald F; Carey, Carolyn M; Nelson, William W; Raffa, Scott J; Winesett, S Parrish

2016-10-01

Profuse bleeding originating from an injured cerebral sinus can be a harrowing experience for any surgeon, particularly during an operation on a young child. Common surgical remedies include sinus ligation, primary repair, placement of a hemostatic plug, and patch or venous grafting that may require temporary stenting. In this paper the authors describe the use of a contoured bioresorbable plate to hold a hemostatic plug in place along a tear in the inferomedial portion of a relatively inaccessible part of the posterior segment of the superior sagittal sinus in an 11-kg infant undergoing hemispherotomy for epilepsy. This variation on previously described hemostatic techniques proved to be easy, effective, and ultimately lifesaving. Surgeons may find this technique useful in similar dire circumstances when previously described techniques are ineffective or impractical.

The hemostatic activity of cryopreserved platelets is mediated by phosphatidylserine-expressing platelets and platelet microparticles.

PubMed

Johnson, Lacey; Coorey, Craig P; Marks, Denese C

2014-08-01

Cryopreservation of platelets (PLTs) at -80°C with dimethyl sulfoxide (DMSO) can extend the shelf life from 5 days to 2 years. Cryopreserved PLTs are reported to have a greater in vivo hemostatic effect than liquid-stored PLTs. As such, the aim of this study was to understand the mechanisms responsible for the hemostatic potential of cryopreserved PLTs and the contribution of the reconstitution solution to this activity. DMSO (5% final concentration) was added to buffy coat-derived PLTs, followed by prefreeze removal of DMSO and storage at -80°C. Cryopreserved PLTs (n=8 per group) were thawed at 37°C, reconstituted with either 1 unit of thawed frozen plasma or PLT additive solution (PAS-G). In vitro assays were performed before freezing and after thawing to assess the hemostatic activity of PLTs. Cryopreserved PLTs expressed high levels of phosphatidylserine and contained significantly more phosphatidylserine-positive PLT microparticles than liquid-stored PLTs. This was accompanied by a significant decrease in the time to clot formation and clot strength, as measured by thromboelastography. The supernatant from cryopreserved PLTs was sufficient to reduce the phosphatidylserine-dependent clotting time and increase the thrombin generation potential. Overall, plasma-reconstituted cryopreserved PLTs were more procoagulant than those reconstituted in PAS-G. PLT cryopreservation results in the generation of phosphatidylserine-expressing PLT microparticles which contribute to the hemostatic activity. Understanding the hemostatic activity of these components may assist in extending the use of these specialized components beyond military applications. © 2014 Australian Red Cross Blood Service. Transfusion © 2014 AABB.

Hypothermia as a cause of coagulopathy during hepatectomy.

PubMed

Lau, Albert Wai-Cheung; Chen, Chia-Chen; Wu, Rick Sai-Chuen; Poon, Kin-Shing

2010-06-01

We report a 27-year-old hemostatically competent female scheduled for partial hepatectomy. During the operation, she experienced an accidental inferior vena cava tear and suffered acute blood loss. After fluid resuscitation and blood transfusion, she developed hypothermia, with a temperature of 33.8 degrees C, and severe coagulopathy with activated clotting time exceeding 1500 seconds measured using the Hemochron Response system (ITC, Edison, NJ, USA). Despite sufficient blood transfusion and correction of her electrolyte imbalance, the poor hemostasis persisted. After per-forming peritoneal lavage with warm saline, her condition dramatically improved and her hypothermia and severe coagulopathy were reversed. 2010 Taiwan Society of Anesthesiologists. Published by Elsevier B.V. All rights reserved.

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

PubMed

Hickman, DaShawn A; Pawlowski, Christa L; Sekhon, Ujjal D S; Marks, Joyann; Gupta, Anirban Sen

2018-01-01

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variation in hospital resource use and cost among surgical procedures using topical absorbable hemostats

PubMed Central

Martyn, Derek; Meckley, Lisa M; Miyasato, Gavin; Lim, Sangtaeck; Riebman, Jerome B; Kocharian, Richard; Scaife, Jillian G; Rao, Yajing; Corral, Mitra

2015-01-01

Background Adjunctive hemostats are used to assist with the control of intraoperative bleeding. The most common types are flowables, gelatins, thrombins, and oxidized regenerated celluloses (ORCs). In the US, Surgicel® products are the only US Food and Drug Administration-approved ORCs. Objective To compare the outcomes of health care resource utilization (HRU) and costs associated with using ORCs compared to other adjunctive hemostats (OAHs are defined as flowables, gelatins, and topical thrombins) for surgical procedures in the US inpatient setting. Patients and methods A retrospective, US-based cohort study was conducted using hospital inpatient discharges from the 2011–2012 calendar years in the Premier Healthcare Database. Patients with either an ORC or an OAH who underwent a cardiovascular procedure (valve surgery and/or coronary artery bypass graft surgery), carotid endarterectomy, cholecystectomy, or hysterectomy were included. Propensity score matching was used to create comparable groups of ORC and OAH patients. Clinical, economic, and HRU outcomes were compared. Results The propensity score matching created balanced patient cohorts for cardiovascular procedure (22,718 patients), carotid endarterectomy (10,890 patients), cholecystectomy (6,090 patients), and hysterectomy (9,348 patients). In all procedures, hemostatic agent costs were 28%–56% lower for ORCs, and mean hemostat units per discharge were 16%–41% lower for ORCs compared to OAHs. Length of stay and total procedure costs for patients treated with ORCs were lower for carotid endarterectomy patients (0.3 days and US$700) and for cholecystectomy patients (1 day and US$3,350) (all P<0.001). Conclusion Costs and HRU for patients treated with ORCs were lower than or similar to patients treated with OAHs. Proper selection of the appropriate hemostatic agents has the potential to influence clinical outcomes and treatment costs. PMID:26604807

Hemostatic abnormalities in dogs with naturally occurring heatstroke.

PubMed

Bruchim, Yaron; Kelmer, Efrat; Cohen, Adar; Codner, Carolina; Segev, Gilad; Aroch, Itamar

2017-05-01

To investigate hemostatic analyte abnormalities and their association with mortality in dogs with naturally occurring heatstroke. Prospective observational study. University teaching hospital. Thirty client-owned dogs with naturally occurring heatstroke. None. Citrated and EDTA blood samples were collected at presentation and at 4, 12, 24, 36, and 48 hours postpresentation (PP). Hemostatic tests performed included platelet count, prothrombin and activated partial thromboplastin times (PT and aPTT, respectively), antithrombin activity (ATA), total protein C activity (tPCA), fibrinogen, and D-dimer concentrations. The overall survival rate was 60% (18/30 dogs). Older age, higher heart rate and rectal temperature at presentation, and time from onset of clinical signs to presentation were significantly associated with mortality. Hemostatic analytes at presentation were not associated with mortality. Prolonged PT and aPTT at 12-24 hours PP, lower tPCA at 12 hours PP, and hypofibrinogenemia at 24 hours PP were significantly (P < 0.05) associated with mortality. Increased D-dimer concentration and low ATA were common at all time points, but were not associated with mortality. The frequency of disseminated intravascular coagulation (DIC) increased in nonsurvivors throughout hospitalization, but the development of DIC was not associated with mortality. The number of abnormal coagulation disturbances during the first 24 hours was significantly higher in nonsurvivors (P = 0.04). Hemostatic derangements are common in dogs with naturally occurring heatstroke. Alterations in PT, aPTT, tPCA, and fibrinogen concentrations appear to be associated with the outcome at 12-24 hours PP, exemplifying the need for serial measurement of multiple laboratory hemostatic tests during hospitalization, even when within reference interval on presentation. The development of DIC, as defined in this cohort, was not associated with mortality; however, nonsurvivors had significantly more coagulation abnormalities during the first 24 hours PP. © Veterinary Emergency and Critical Care Society 2017.

Comparison of hemostatic properties between collagen and synthetic buttress materials used in staple line reinforcement in a swine splenic hemorrhage model.

PubMed

Spector, David; Perry, Zvi; Konobeck, Tracy; Mooradian, Daniel; Shikora, Scott

2011-04-01

The use of staplers in gastrointestinal surgery is widespread, especially in advanced laparoscopic procedures. Staple line reinforcement with a buttress reduces bleeding and associated complications through a combination of factors. The intrinsic hemostatic properties of buttress materials have not been examined. This study examined the intrinsic hemostatic properties of two different types of material used in buttressing in an accepted hemostasis model that does not involve stapling or its effects by compression. An acellular collagen buttress (Veritas) and a synthetic polymer buttress (Duet) were compared to two commonly used hemostatic agents, Syvek and Surgicel, with gauze as control. In a swine capsular stripping hemostasis model, a 1 × 1 cm section of spleen capsule was removed and used as a source of bleeding, with one patch of material tested per bleeding site. A total of 51 wounds were created in five pigs (each patch n = 10, control n = 11). Hemostatic efficacy was assessed by quantitating the number of applications and total time needed for bleeding to stop. The mean time needed for hemostasis for Syvek and Veritas patches was significantly less than gauze, Duet and Surgicel (4.02, 4.51 vs. 8.97, 9.22, and 10.30 min respectively; p < 0.05). The Syvek and Veritas patches required significantly fewer applications than gauze, Duet™ and Surgicel (1.7, 2.2 vs. 4.1, 4.6, and 4.9 respectively; p < 0.01). The intrinsic hemostatic properties of different buttressing materials vary widely. In this study, a collagen buttress was significantly better at promoting hemostasis than the synthetic buttress material in a nonstapling model. This could be another factor to consider when choosing a buttress for staple line reinforcement.

The effects of QuikClot Combat Gauze on hemorrhage control in the presence of hemodilution.

PubMed

Johnson, Don; Agee, Samantha; Reed, Amanda; Gegel, Brian; Burgert, James; Gasko, John; Loughren, Michael

2012-01-01

Although hemostatic agents may be effective at stopping hemorrhage, they may fail because of hemodilution from intravenous fluids. The purpose of this study was to investigate the effects of QuikClot Combat Gauze (QCG) on rebleeding in a class II hemorrhage in the presence of hemodilution in a lethal femoral injury. This was a prospective experimental, between swine subjects design. Pigs were assigned to one of two groups: QCG (n=15) or control (n=15). Thirty percent of the pig's blood was exsanguinated and then a 3:1 ratio of ringers lactate was administered. A groin injury was created by transecting the femoral artery and vein to simulate a battlefield injury and allowed to bleed for one minute. After one minute of hemorrhage, proximal pressure was applied to the injury, and QCG was placed into the wound followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agent. For both groups, 5 minutes of direct pressure was applied to the wound followed by a standard pressure dressing. Dressings were removed after 30 minutes, and the amount of hemorrhage was calculated in milliliters for each group for a period of 5 minutes. An activated clotting time was used to exclude any pigs with coagulation pathology. A multivariate analysis of variance indicated that there were no significant differences in the groups relative to weight, amount of one minute hemorrhage, fluid deficit replacement, blood volume, and the activated clotting time (P>.05) indicating that the groups were equivalent on these parameters. A t test indicated that there was significantly less bleeding (P=.002) in the QCG group (36 mL±112 mL) compared to the control group (340 mL±297 ml). QCG produces a robust clot that can more effectively tolerate hemodilution compared to a control group.

Structure/function relations of hemostatic nonwoven dressings based on greige cotton

USDA-ARS?s Scientific Manuscript database

A variety of natural and synthetic fibers are employed in hemostatic dressings. Here we demonstrate the use of greige cotton as a functional fiber, which when combined with hydrophilic and hydrophobic fibers in hydroentangled nonwoven materials, promotes accelerated clotting. A biophysical approach...

Use of absorbable hemostatic gauze with medical adhesive is effective for achieving hemostasis in presacral hemorrhage.

PubMed

Zhang, Chang-Hua; Song, Xin-Ming; He, Yu-Long; Han, Fanghai; Wang, Liang; Xu, Jian-Bo; Chen, Chuang-Qi; Cai, Shi-Rong; Zhan, Wen-Hua

2012-04-01

Management of presacral hemorrhage is always challenging. Herein we describe the use of an absorbable hemostatic gauze with α-cyanoacrylate medical adhesive to achieve hemostasis. In this study, we conducted total mesorectal excision for the treatment of rectal cancer in 258 patients from March 2006 to May 2009. Intraoperative presacral hemorrhage developed in 5 (2%) patients during rectal mobilization. In these 5 patients, massive bleeding could not be controlled by pressure and pelvic packing with gauze. An absorbable hemostatic gauze spread with medical adhesive was compressed onto the bleeding vessel for at least 20 minutes. Hemostasis was achieved successfully and was maintained during the surgery. Patients recovered uneventfully and no postoperative events were noted. The use of an absorbable hemostatic gauze with medical adhesive is a simple and effective method for achieving hemostasis when massive presacral hemorrhage occurs. However, its effectiveness needs to be confirmed in a controlled study in a properly selected patient population. Copyright © 2012. Published by Elsevier Inc.

Serological analysis of patients treated with a new surgical hemostat containing bovine proteins and autologous plasma.

PubMed

Nelson, P A; Powers, J N; Estridge, T D; Elder, E A; Alea, A D; Sidhu, P K; Sehl, L C; DeLustro, F A

2001-01-01

A randomized, controlled clinical study of the management of diffuse bleeding with CoStasis surgical hemostat, a new hemostat containing bovine thrombin and collagen with the patient's own plasma, included patients undergoing cardiac, hepatic, iliac, and general surgery. Sera from 92 patients treated with CoStasis and 84 control patients were collected preoperatively and at a post surgical follow-up of 8 weeks. Among the control group, 57 patients were treated with Instat collagen sponge in noncardiac indications. Results showed that antibody responses in the CoStasis clinical study were similar to the reported literature for all antigens screened and were not associated with any adverse reactions. The bovine thrombin preparations in CoStasis and other commercially available thrombins were compared with the use of SDS-PAGE and Western blot analyses. Within this clinical study, CoStasis was shown to be a safe and effective hemostatic product containing bovine thrombin and bovine collagen and no pooled human blood products. Copyright 2001 John Wiley & Sons, Inc.

Evaluation of Shear Bond Strength of Total- and Self-etching Adhesive Systems after Application of Chlorhexidine to Dentin Contaminated with a Hemostatic Agent

PubMed Central

Sharafeddin, Farahnaz; Farhadpour, Hajar

2015-01-01

Statement of the Problem Hemostatic agents may influence the bond strength of different bonding agents. Also, chlorhexidine has shown positive effects on bond strength values and their combination effect has not been reported yet. Purpose The aim of this study was to evaluate the effect of contamination with a hemostatic agent on shear bond strength (SBS) of total- and self-etching adhesive systems and the effect of chlorhexidine application after removal of the hemostatic agent. Materials and Method In this experimental study, the occlusal enamel of each sixty caries-free mandibular molars was removed and their midcoronal dentin was exposed. The specimens were then mounted in auto-polymerizing resin 1mm apical to CEJ. Then, the specimens were divided into 6 groups (n=10) based on contamination with a hemostatic agent (H), application of chlorhexidine (CHX) and the adhesive system used; and then were classified as Group 1: Adper Single Bond (ASB); Group 2: H+ASB; Group 3: H+0.2% CHX+ASB; Group 4: Clearfil SE Bond (CSB); Group 5: H+CSB; Group 6: H+0.2% CHX+CSB. Then, composite resin rods (4×2 mm) were built up on the dentin surfaces and after thermocycling, the SBS (MPa) was evaluated. Statistical analysis was performed using two-way ANOVA and post hoc Tukey tests (p< 0.05). Results There were statistically significant differences between bond strength values of group 1 (ASB) and group 2 (H+ASB) (p< 0.001) and group 1 (ASB) and group 3 (H+CHX+ASB) (p< 0.001). Similarly, significant differences were seen between group 4 (CSB) and group 5 (H+CSB) (p< 0.001) and between group 4 (CSB) and group 6 (H+CHX+CSB) (p< 0.001). Conclusion Contamination with hemostatic agent reduced the SBS of both total- and self-etching adhesive systems. In addition, application of chlorhexidine after the removal of hemostatic agent had a negative effect on SBS of total- and self-etching adhesive systems. PMID:26331146

Use of topical hemostatic agents in gynecologic surgery.

PubMed

Wysham, Weiya Z; Roque, Dario R; Soper, John T

2014-09-01

Sutures, hemoclips, and electrocautery are the primary mechanisms used to achieve hemostasis during gynecologic surgery, but in situations in which these are inadequate or not feasible, an array of hemostatic agents are available to help achieve hemostasis. These agents include physical agents such as cellulose, collagen, or gelatin products as well as biologic agents such as thrombin and fibrin products. Limited data are available on many of these agents, although their use is increasing, sometimes at high costs. In gynecologic surgery, hemostatic agents are likely most effective when used in areas of oozing or slow bleeding and as an adjunct to conventional surgical methods of hemostasis.

[Preliminary evaluation on seroma prevention and treatment with transposition of tissue flaps and arista hemostatic powder].

PubMed

Zhang, Ruming; Tan, Yiwen; Wang, Heqi

2006-12-01

To investigate and evaluate prevention and treatment of seroma by transposition of tissue flaps and Arista hemostatic powder after regional lymph node resection in patients with malignant tumors. Twelve patients (6 males, 6 females; aged 31-81 years, with metastatic tumors underwent prevention and treatment of seroma with the tissue flaps and Arista hemostatic powder spray after regional lymph node resection. The metastatic tumors involved the axilla in 1 patient with breast carcinoma, the iliac and inguinal regions in 2 patients with carcinomas of the uterine cervix and the rectum, and the inguinal region in 9 patients, including 4 patients with malignant fibrous histiocytoma(3 in the thigh, 1 in the leg), 2 patients with squamous carcinomas in the leg, 1 patient with synovial sarcoma in the knee, 1 patient with epithelioid sarcoma in the leg, and 1 patient with malignant melanoma in the foot. As for the lymph node removal therapy. 1 patient underwent axillary lymph node removal, 2 patients underwent lymph node removal in theiliac and inguinal regions, and 9 patients underwent lymph node removal in the inguinal region. Meanwhile, of the 12 patients, 6 patients underwent transposition of sartorius flaps with Arista hemostatic powder, 3 patients underwent transposition of the rectus abdominis myocutaneous flaps (including 2 patients treated with Arista spray befor the wound closure and 1 patient treated by transposition of local skin flaps with Arista spray used again),and 3 patients underwent only the suturing of the wounds combined with Arista. At the same time, of the 12 patients,only 4 patient underwent the transplantation of artificial blood vessels. The follow-up for 2-10 months after operation revealed that 10 patients, who had received the transposition of tissue flaps and the spray of Arista hemostatic powder, had the first intention of the incision heal with seroma cured. Nine patients were given a preventive use of Arista hemostatic powder and therefore no seroma developed. The combined use of the transposition of tissue flaps and Arista hemostatic powder spray achieved a success rate of 100% in the prevention or treatment of seroma. However, 1 patient developed microcirculation disturbance 24 hours after operation and underwent disarticulation of the hip; 1 patient developed pelvic cavity hydrops and died 10 months after operation. The combined use of transposition of tissue flaps and Arista hemostatic powder spray can effectively prevent or treat seroma after regional lymph node removal in a patient with malignant tumor.

Application of Absorbable Hemostatic Materials Observed in Thyroid Operation

NASA Astrophysics Data System (ADS)

Li, Yan-Ming; Liang, Zhen-Zhen; Song, Yan

2016-05-01

To observe the application effects of the absorbable hemostatic materials in thyroid operation. Methods: From May 2014 to January 2015, 100 patients with thyroid surgery in our university affiliated hospital were selected as the research object. Randomly divided into experimental group and control group, 50 cases in each group. Application of absorbable hemostatic hemostatic materials in the experimental group during the operation, the control group using the traditional mechanical methods of hemostasis hemostasis to observe the operation time, bleeding volume, postoperative drainage volume, complications and hospital stay of the two groups. Results: The operation time, bleeding volume, postoperative drainage and hospital stay in the experimental group were significantly lower in the study group than in the control group, and the difference between the two groups was statistically significant (P< 0.05); The satisfaction of patients in the experimental group was significantly higher than that in the control group, the difference was statistically significant in the two groups (P < 0.05); There was no significant difference in the incidence of wound bleeding complications between the study group and the control group (P > 0.05). Conclusion: Absorbable hemostatic materials can effectively shorten the operation time, reduce intraoperative blood loss and postoperative drainage, reduce the length of hospital stay and improve the success rate of surgery and patient satisfaction, which is worthy to be popularized in clinical thyroid surgery.

Properties of novel bone hemostat prepared using sugar-modified hydroxyapatite, phosphoryl oligosaccharides of calcium and thermoplastic resin

NASA Astrophysics Data System (ADS)

Mimira, Tokio; Umeda, Tomohiro; Musha, Yoshiro; Itatani, Kiyoshi

2013-12-01

A novel hemostatic agent was prepared using phosphoryl oligosaccharides of calcium (POs-Ca), hydroxyapatite (Ca10(PO4)6(OH)2; HAp) obtained by the hydrolysis of POs-Ca or sugar-containing HAp (s-HAp; 60.3 mass% calcium-deficient HAp and 39.5 mass% organic materials, Ca/P ratio = 1.56) and thermoplastic resin (the mixture of random copolymer of ethylene oxide/propylene oxide (EPO) and polyethylene oxide (EO); EPO : EO : water = 25 : 15 : 60 (mass ratio); 25EPO-15EO). The gel formed by mixing 25EPO-15EO with water (25EPO-15EO/water mass ratio: 0.20) was flash frozen at -80°C, freeze-dried at -50°C for 15 h and then ground using mixer. The consistency conditions of hemostats mixed with POs-Ca or s-HAp were optimized for the practical uses. The mean stanching times of hemostats were: s-HAp/25EPO-15EO (8.2 h; s-HAp/25EPO-15EO = 0.20) > 25EPO-15EO (5.3 h) > POs-Ca/25EPO-15EO (4.7 h; POs-Ca/25EPO-15EO = 0.20). The gentamicin, a typical antibiotic agent, loaded s-HAp/25EPO-15EO composite hemostat showed the steady state releasing in phosphate buffered saline till 10 h immersion at 37.0°C.

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

Safety and usability of hemostats, sealants, and adhesives.

PubMed

Burks, Sandra; Spotnitz, William

2014-08-01

Hemostats, sealants, and adhesives are an integral part of surgical patient care. Nurses who have knowledge about these agents can better help ensure safe, efficient surgical patient care. As a caregiver and patient advocate, the perioperative nurse must understand the most current information about these agents and be prepared to facilitate the transfer of this knowledge to all caregivers. Information about these agents, including the contraindications, warnings, and precautions associated with their use as well as their preparation and application, is provided here. Algorithms designed to clarify the best options for using hemostats, sealants, and adhesives are included as well. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

New generation tissue sealants and hemostatic agents: innovative urologic applications.

PubMed

Traver, Michael A; Assimos, Dean G

2006-01-01

Control of blood loss during urologic surgery is paramount to the success of patient recovery. Hemostatic agents and tissue sealants are used routinely to prevent excess blood loss and in reconstruction during surgical repair. Some of the available products include thrombin sealant, fibrin glue, bovine serum/albumin/glutaraldehyde, and gelatin matrix. Each of these agents differs in mechanism, cost, and application. Complications can include allergic reactions or thromboembolism and the risk of contracting bovine spongiform encephalitis or hepatitis. Many new hemostatic agents are being developed and approved. The benefits and risks of use of these agents versus conventional treatment need to be considered on a case-by-case basis by the surgeon.

Release abilities of adenosine diphosphate from phospholipid vesicles with different membrane properties and their hemostatic effects as a platelet substitute.

PubMed

Okamura, Yosuke; Katsuno, Shunsuke; Suzuki, Hidenori; Maruyama, Hitomi; Handa, Makoto; Ikeda, Yasuo; Takeoka, Shinji

2010-12-20

We have constructed phospholipid vesicles with hemostatic activity as a platelet substitute. The vesicles were conjugated with a dodecapeptide (HHLGGAKQAGDV, H12), which is a fibrinogen γ-chain carboxy-terminal sequence (γ400-411). We have recently exploited these vesicles as a potential drug delivery system by encapsulation of adenosine 5'-diphosphate (ADP) (H12-(ADP)-vesicles). Here we explore the relationship between the ADP release from H12-(ADP)-vesicles with different membrane properties and their hemostatic effects. In total, we prepared five kinds of H12-(ADP)-vesicles with different lamellarities and membrane flexibilities. By radioisotope-labeling, we directly show that H12-(ADP)-vesicles were capable of augmenting platelet aggregation by releasing ADP in an aggregation-dependent manner. The amount of ADP released from the vesicles was dependent on their membrane properties. Specifically, the amount of ADP released increased with decreasing lamellarity and tended to increase with increasing membrane flexibility. Our in vivo results clearly demonstrated that H12-(ADP)-vesicles with the ability to release ADP exert considerable hemostatic action in terms of correcting prolonged bleeding time in a busulphan-induced thrombocytopenic rat model. We propose a recipe to control the hemostatic abilities of H12-(ADP)-vesicles by modulating ADP release based on membrane properties. We believe that this concept will be invaluable to the development of platelet substitutes and other drug carriers. Copyright © 2010 Elsevier B.V. All rights reserved.

Hemostatic efficacy of EVARREST™, Fibrin Sealant Patch vs. TachoSil® in a heparinized swine spleen incision model.

PubMed

Matonick, John P; Hammond, Jeffrey

2014-12-01

First-generation single-component hemostats such as oxidized regenerated cellulose (ORC), fibrin, collagen, and gelatin have evolved into second and third generations of combination hemostats. This study compares two FDA approved products, EVARREST™, Fibrin Sealant Patch, a hemostat comprised of a matrix of nonwoven polyglactin 910 embedded in ORC coated with human fibrinogen and thrombin to TachoSil® medicated sponge, an equine collagen pad coated with human fibrinogen and thrombin. Swine were anticoagulated with heparin to 3X their baseline activated clotting time and a 15 mm long × 3 mm deep incision was made to create a consistent moderate bleeding pattern. Test material was then applied to the wound site and compressed manually for 3 min with just enough pressure to prevent continued bleeding. Hemostatic effectiveness was evaluated at 3 min and 10 min. At 3 min, the hemostasis success rate was 86% in the EVARREST™ group and 0% in the TachoSil® group, p < .0001. The overall success rate at 10 min was 100% with EVARREST™ and 4% with TachoSil®, p < .0001. Adhesive failure, in which the test material did not stick to the tissue, occurred in 96% of TachoSil® sites. In contrast, 100% of the EVARREST™ applications adhered to the test site. EVARREST™, Fibrin Sealant Patch demonstrated greater wound adhesion and more effective hemostasis than TachoSil®. Adhesive failure was the primary failure mode for TachoSil® in this model.

Acute Management of Hemostasis in Patients With Neurological Injury.

PubMed

Baharoglu, M Irem; Brand, Anneke; Koopman, Maria M; Vermeulen, Marinus; Roos, Yvo B W E M

2017-10-01

Neurological injuries can be divided into those with traumatic and nontraumatic causes. The largest groups are traumatic brain injury (TBI) and nontraumatic stroke. TBI patients may present with intracranial hemorrhages (contusions, or subdural or epidural hematomas). Strokes are ischemic or hemorrhagic. In all these disorders, thrombosis and hemostasis play a major role. Treatment aims to either cease bleeding and/or restore perfusion. We reviewed hemostatic and thrombolytic therapies in patients with neurological injuries by MEDLINE and EMBASE search using various key words for neurological disorders and hemostatic therapies restricted to English language and human adults. Review of articles fulfilling inclusion criteria and relevant references revealed that, in patients with ischemic stroke, intravenous thrombolytic therapy with recombinant tissue plasminogen activator within 4.5-5 hours after onset of symptoms improves clinical outcome. In contrast, there are no hemostatic therapies that are proven to improve clinical outcome of patients with hemorrhagic stroke or TBI. In patients with hemorrhagic stroke who use vitamin K antagonist or direct oral anticoagulants, there is evidence that specific reversal therapies improve hemostatic laboratory parameters but without an effect on clinical recovery. In patients with hemorrhagic stroke or TBI who use concomitant antiplatelet therapy, there is evidence for harm of platelet transfusion. In patients with aneurysmal subarachnoid hemorrhage, tranexamic acid was shown to reduce rebleeding rate without improving clinical outcome. The effects of tranexamic acid in patients with TBI are still under investigation. We conclude that, in patients with ischemic stroke, thrombolytic therapy improves outcome when given within 4.5-5 hours. In hemorrhagic stroke and TBI, most hemostatic therapies improved or corrected laboratory parameters but not clinical outcome. Currently, in several trials, the effects of tranexamic acid are being studied of which the results are eagerly awaited. Because improving clinical outcome should be the goal of new therapies, we encourage to use clinical outcome scales as the primary outcome measure in trials that investigate effects of hemostatic therapies in patients with neurological injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of External Hemorrhage in Tactical Combat Casualty Care: Chitosan-Based Hemostatic Gauze Dressings--TCCC Guidelines-Change 13-05.

PubMed

Bennett, Brad L; Littlejohn, Lanny F; Kheirabadi, Bijan S; Butler, Frank K; Kotwal, Russ S; Dubick, Michael A; Bailey, Jeffrey A

2014-01-01

Hemorrhage remains the leading cause of combat death and a major cause of death from potentially survivable injuries. Great strides have been made in controlling extremity hemorrhage with tourniquets, but not all injuries are amenable to tourniquet application. Topical hemostatic agents and dressings have also contributed to success in controlling extremity and compressible junctional hemorrhage, and their efficacy continues to increase as enhanced products are developed. Since the addition of Combat Gauze™ (Z-Medica Corporation, Wallingford, CT, USA; http://www.z-medica.com/) in April 2008 to the Tactical Combat Casualty Care (TCCC) Guidelines, there are consistent data from animal studies of severe hemorrhage that chitosan-based hemostatic gauze dressings developed for battlefield application are, at least, equally efficacious as Combat Gauze. Successful outcomes are also reported using newer chitosan-based dressings in civilian hospital-based surgical case reports and prehospital (battlefield) case reports and series. Additionally, there have been no noted complications or safety concerns in these cases or across many years of chitosan-based hemostatic dressing use in both the military and civilian prehospital sectors. Consequently, after a decade of clinical use, there is added benefit and a good safety record for using chitosan-based gauze dressings. For these reasons, many specific US military Special Operations Forces, NATO militaries, and emergency medical services (EMS) and law enforcement agencies have already implemented the widespread use of these new recommended chitosan-based hemostatic dressings. Based on the past battlefield success, this report proposes to keep Combat Gauze as the hemostatic dressing of choice along with the new addition of Celox™ Gauze (Medtrade Products Ltd., Crewe, UK; http://www.celoxmedical.com/usa/products /celox-gauze/) and ChitoGauze® (HemCon Medical Technologies, Portland, OR, USA; http://www.hemcon.com/) to the TCCC Guidelines. 2014.

Kaolin-based hemostatic dressing improves hemorrhage control from a penetrating inferior vena cava injury in coagulopathic swine.

PubMed

Koko, Kiavash R; McCauley, Brian M; Gaughan, John P; Nolan, Ryan S; Fromer, Marc W; Hagaman, Ashleigh L R; Choron, Rachel L; Brown, Spencer A; Hazelton, Joshua P

2017-07-01

Retrohepatic inferior vena cava (RIVC) injuries are often lethal due to challenges in obtaining hemorrhage control. We hypothesized that packing with a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT) would improve hemorrhage control from a penetrating RIVC injury compared with packing with standard laparotomy sponges alone. Twelve male Yorkshire pigs received a 25% exchange transfusion of blood for refrigerated normal saline to induce a hypothermic coagulopathy. A laparotomy was performed and a standardized 1.5 cm injury to the RIVC was created which was followed by temporary abdominal closure and a period of uncontrolled hemorrhage. When the mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock, the abdomen was re-entered, and the injury was treated with perihepatic packing using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid solution. The two groups were compared using the Wilcoxon rank sum test and Fisher exact test. A p value of 0.05 or less was considered statistically significant. There was no difference in the animal's temperature, heart rate, mean arterial pressure, cardiac output, and blood loss at baseline or before packing was performed (all p > 0.05). In the laparotomy sponge group, five of six pigs survived the entire study period, whereas all six pigs treated with kaolin-based D2 hemostatic dressings survived. Importantly, there was significantly less blood loss after packing with the new hemostatic kaolin-based dressing compared with packing with laparotomy sponge (651 ± 180 mL vs. 1073 ± 342 mL; p ≤ 0.05). These results demonstrate that the use of this new hemostatic kaolin-based dressing improved hemorrhage control and significantly decreased blood loss in this penetrating RIVC model. This is basic science research based on a large animal model, level V.

Combination Effect of Hemostatic and Disinfecting Agents on Micro-leakage of Restorations Bonded with Different Bonding Systems

PubMed Central

H, Farhadpour; F, Sharafeddin; Sc, Akbarian; B, Azarian

2016-01-01

Statement of Problem: Hemostatic agents may affect the micro-leakage of different adhesive systems. Also, chlorhexidine has shown positive effects on micro-leakage. However, their interaction effect has not been reported yet. Objectives: To evaluate the effect of contamination with a hemostatic agent on micro-leakage of total- and self-etching adhesive systems and the effect of chlorhexidine application after the removal of the hemostatic agent. Materials and Methods: Standardized Class V cavity was prepared on each of the sixty caries free premolars at the cemento-enamel junction, with the occlusal margin located in enamel and the gingival margin in dentin. Then, the specimens were randomly divided into 6 groups (n = 10) according to hemostatic agent (H) contamination, chlorhexidine (CHX) application, and the type of adhesive systems (Adper Single Bond and Clearfil SE Bond) used. After filling the cavities with resin composite, the root apices were sealed with utility wax. Furthermore, all the surfaces, except for the restorations and 1mm from the margins, were covered with two layers of nail varnish. The teeth were immersed in a 0.5% basic fuschin dye for 24 hours, rinsed, blot-dried and sectioned longitudinally through the center of the restorations bucco- lingualy. The sections were examined using a stereomicroscope and the extension of dye penetration was analyzed according to a non-parametric scale from 0 to 3. Statistical analysis was performed using Kruskal-Wallis test and Mann-Whitney U-test. Results: While ASB group showed no micro-leakage in enamel, none of the groups showed complete elimination of micro-leakage from the dentin. Regarding micro-leakage at enamel, and dentin margins, there was no significant difference between groups 1 and 2, 1 and 3, and 2 and 3 (p > 0.05). A significantly lower micro-leakage at the enamel and dentin margins was observed in group 3, compared to group 6. No significant difference was observed between groups 4 and 5 in enamel (p = 0.35) and dentin (p = 0.34). Group 6 showed significantly higher micro-leakage, compared to group 4 and 5 (p < 0.05). Conclusions: Hemostatic agent contamination had no significant effect on micro-leakage of total- and self-etching adhesive systems. Application of chlorhexidine after the removal of hemostatic agent increased micro-leakage in self-etching adhesives but did not affect when total-etching was used. PMID:28959756

Epidural spinal cord compression with neurologic deficit associated with intrapedicular application of hemostatic gelatin matrix during pedicle screw insertion.

PubMed

Buchowski, Jacob M; Bridwell, Keith H; Lenke, Lawrence G; Good, Christopher R

2009-06-01

Case report. In order to demonstrate the dangers of intrapedicular application of a hemostatic gelatin matrix to decrease blood loss during pedicle screw insertion, we present 2 patients who--as a result of inadvertent extravasation of the matrix into the spinal canal--developed epidural spinal cord compression (ESCC) requiring emergent decompression. Variety of hemostatic agents can control bleeding during pedicle screw insertion. We have often used a hemostatic gelatin matrix to decrease bleeding from cannulated pedicles by injecting the material into the pedicle after manually palpating the pedicle. Medical records and radiographic studies of 2 patients with AIS who underwent surgical treatment of their deformity and developed a neurologic deficit due to extravasation of FloSeal were reviewed. A 15 year-old male underwent T4 to L2 posterior spinal fusion (PSF). During pedicle screw insertion, a change in NMEPs and SSEPs was noted. A wake-up test confirmed bilateral LE paraplegia. Screws were removed and no perforations were noted on manual palpation. MRI showed T7 to T10 ESCC. He underwent a T5 to T10 laminectomy and hemostatic gelatin matrix noted in the canal and was evacuated. He was ambulatory at 2 weeks and by 3 months he had complete recovery. The second patient was a 15 year-old female who underwent T4 to L1 PSF. Following screw insertion, deterioration in NMEPs and SSEPs was noted. Screws were removed and SCM data returned to baseline. Except for 3 screws that had an inferior breach (Left T7 and Bilateral T8), screws were reinserted and remainder of the surgery was uneventful. Postoperative examination was normal initially but 2 days later, she developed left LE numbness/weakness. Implants were removed and MRI showed T4 to T9 ESCC.She underwent a left (concave) T4 to T9 hemilaminectomy. Hemostatic gelatin matrix was noted and was evacuated. Six weeks following surgery, she had a complete neurologic recovery. The use of a hemostatic gelatin matrix to decrease bleeding from cannulated pedicles during pedicle screw insertion can result in inadvertent extravasation into the spinal canal resulting in ESCC even in the absence of an apparent medial pedicle breach. Given the dangers associated with the technique, we recommend that gelatin matrix products be used judiciously during pedicle screw insertion.

CLONING, EXPRESSION, AND HEMOSTATIC ACTIVITIES OF A DISINTEGRIN, r-MOJASTIN 1, FROM THE MOHAVE RATTLESNAKE (Crotalus scutulatus scutulatus)

PubMed Central

Sánchez, Elda E.; Lucena, Sara E.; Reyes, Steven; Soto, Julio G.; Cantu, Esteban; Lopez-Johnston, Juan Carlos; Guerrero, Belsy; Salazar, Ana Maria; Rodríguez-Acosta, Alexis; Galán, Jacob A.; Tao, W. Andy; Pérez, John C.

2012-01-01

Interactions with exposed subendothelial extracellular proteins and cellular integrins (endothelial cells, platelets and lymphocytes) can cause alterations in the hemostatic system associated with atherothrombotic processes. Many molecules found in snake venoms induce pathophysiological changes in humans, cause edema, hemorrhage, and necrosis. Disintegrins are low molecular weight, non-enzymatic proteins found in snake venom that mediate changes by binding to integrins of platelets or other cells and prevent binding of the natural ligands such as fibrinogen, fibronectin or vitronectin. Disintegrins are of great biomedical importance due to their binding affinities resulting in the inhibition of platelet aggregation, adhesion of cancer cells, and induction of signal transduction pathways. RT-PCR was used to obtain a 216 bp disintegrin cDNA from a C. s. scutulatus snake venom gland. The cloned recombinant disintegrin called r-mojastin 1 codes for 71 amino acids, including 12 cysteines, and an RGD binding motif. r-Mojastin 1 inhibited platelet adhesion to fibronectin with an IC50 of 58.3 nM and ADP-induced platelet aggregation in whole blood with an IC50 of 46 nM. r-Mojastin 1 was also tested for its ability to inhibit platelet ATP release using PRP resulting with an IC50 of 95.6 nM. MALDI-TOF mass spectrum analysis showed that r-mojastin has a mass of 7.9509 kDa. PMID:20598348

Identifying novel genetic determinants of hemostatic balance.

PubMed

Ginsburg, D

2005-08-01

Incomplete penetrance and variable expressivity confound the diagnosis and therapy of most inherited thrombotic and hemorrhagic disorders. For many of these diseases, some or most of this variability is determined by genetic modifiers distinct from the primary disease gene itself. Clues toward identifying such modifier genes may come from studying rare Mendelian disorders of hemostasis. Examples include identification of the cause of combined factor V and VIII deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1 and MCFD2. These proteins form a cargo receptor that facilitates the transport of factors V and VIII, and presumably other proteins, from the ER to the Golgi. A similar positional cloning approach identified ADAMTS-13 as the gene responsible for familial TTP. Along with the work of many other groups, these findings identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for hemostasis. Recent advances in mouse genetics also provide powerful tools for the identification of novel genes contributing to hemostatic balance. Genetic studies of inbred mouse lines with unusually high and unusually low plasma VWF levels identified polymorphic variation in the expression of a glycosyltransferase gene, Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans.

Associations between vitamin K status and hemostatic and inflammatory biomarkers in community-dwelling adults: The multi-ethnic study of atherosclerosis

USDA-ARS?s Scientific Manuscript database

Vitamin K is integral to hemostatic function, and in vitro and animal experiments suggest that vitamin K can suppress production of inflammatory cytokines. To test the hypothesis that higher vitamin K status is associated with lower hemostasic activation and inflammation in community-dwelling adults...

Intentional placental removal on suspicious placenta accreta spectrum: still prohibited?

PubMed

Matsubara, Shigeki; Takahashi, Hironori

2018-01-01

Intentional placental removal for abnormally invasive placenta (AIP) is fundamentally abandoned at planned surgery for it. Whether this holds true even after recent introduction of various hemostatic procedures is unclear. We discussed on this issue based on our own experiences and also on the recent reports on various hemostatic procedures. Studies directly answering this question have been lacking. We must weigh the balance between the massive bleeding and possibility of uterus-preservation when intentional placental removal strategy is employed. An almost forgotten strategy, the "intentional placental removal" for planned AIP surgery may regain its position when appropriate hemostatic procedures are concomitantly used depending on the situation. Even employing this strategy, quick decision to perform hysterectomy under multidisciplinary team may be important.

Effects of Contamination by Hemostatic Agents and Use of Cleaning Agent on Etch-and-Rinse Dentin Bond Strength.

PubMed

Pucci, César Rogério; Araújo, Rodrigo Maximo de; Lacerda, Ana Julia Farias de; Souza, Mirella Anjos de; Huhtala, Maria Filomena Rocha Lima; Feitosa, Fernanda Alves

2016-01-01

The aim of this study was to evaluate the influence of contamination by hemostatic agents and rinsing with chlorhexidine on bond strength between dentin and resin composite. Ninety-six bovine teeth were sectioned to expose a flat dentin surface area. A standardized cavity with 2.0 mm in thickness, superficial diameter of 4.0 mm and bottom diameter of 3.0 mm was prepared with a diamond bur in each dentin specimen. The teeth were divided into four groups according to the hemostatic employed: G1: control; G2: use of ViscoStat, Ultradent; G3: Hemosthasegel, FGM; and G4: Hemostop, Dentsply. The groups were divided into two subgroups according to the cleaning protocol method (n=12): A: without any further cleaning; and B: cleaning with chlorhexidine at 0.2%. All cavities were filled using a dentin adhesive and a resin composite, following the manufacturer's instructions. After 24 h, the specimens were aged by thermal and mechanical cycling. The bond strength was determined by the push out bond test (MPa), Statistical analysis was performed using two-way ANOVA and Tukey test (p<0.05). Statistically significant differences were detected among all groups treated with hemostatic agents and the control group. The post-hoc test showed that cleaning the cavity with chlorhexidine significantly improves the bond strength between dentin and resin composite. Our results suggested that the use of chlorhexidine can reestablish the bond strength between dentin and resin composite when a hemostatic agent was applied.

Managing port-site bleeding during less invasive coronary artery bypass grafting.

PubMed

Kiani, Soroosh; Brecht, Mary-Lynn; Lovinger, Katherine; Poston, Robert S

2012-10-01

Robotic-assisted coronary artery bypass grafting (r-CABG) requires the placement of ports bluntly through the chest wall. When removed, these ports create bleeding sites that can be difficult to detect and treat. This study evaluated whether a topical hemostatic agent placed locally within these sites helps to reduce bleeding and blood product requirements. We retrospectively analyzed outcomes for r-CABG cases where 5 mL of a flowable hemostatic agent was injected locally within all port sites (hemostat group, n = 62) compared with patients whose port sites were untreated (controls, n = 131). Outcomes included chest tube output, red blood cell (RBC) transfusions, length of hospital stay, and the risk of reoperation for bleeding. Analyses were adjusted for risk factors known to influence bleeding and Society of Thoracic Surgeons (STS) risk score as a weighted composite of variables, which controls for patient and clinical variables. The 2 study groups had similar baseline characteristics and underwent the same r-CABG procedure. The hemostat group had significant reductions in RBC transfusion (24.2% versus 40.8% receiving blood; P = .026; 0.44 versus 1.39 U transfused postoperatively, P = .024). After adjustment for bleeding risks (using STS risk score), differences in transfusions remained significant. Reoperation rates for bleeding, length of stay, chest tube drainage, and intraoperative transfusions were not significantly different in the 2 groups. There was significantly reduced postoperative bleeding and less exposure to blood products in the hemostat group. These findings suggest that undetected bleeding from sites used for port access serves as an underappreciated source of morbidity after r-CABG.

Effectiveness of the addition of Lidocaine to a hemostatic, bioresorbable putty in the treatment of iliac crest donor site pain.

PubMed

Müller, Marc Andreas; Mehrkens, Arne; Zürcher, Roman; Vavken, Patrick; Valderrabano, Victor

2014-12-08

The harvest of iliac crest bone grafts (ICBG) is associated with relevant donor site pain, but may be lowered by the application of lidocaine loaded on biodegradable, hemostatic putty for sustained local analgesic release. The goal of this double-blind controlled trial was to assess the efficacy of adding lidocaine to a hemostatic putty (Orthostat ™) to treat donor site pain following harvest of ICBG in foot and ankle procedures. After ICBG harvest during a foot and ankle procedure, the resulting bone defect was either filled with Orthostat™ (n = 7) or with the same hemostatic putty loaded with lidocaine (Orthostat-L™, n = 7). During the first 72 postoperative hours, donor site and surgical site pain were managed by patient controlled morphine delivery and a peripheral nerve block. Donor site pain was periodically quantified on a Visual Analog (VAS) and a Wong Baker FACES scale. Pain scores were plotted over time to calculate the area under the curve (AUC) to quantify the overall pain experienced in specific time intervals. Orthostat-L™ significantly reduced donor site pain over the first 12 hours postoperatively as evidenced by a significant decrease of the AUC in both VAS (p = 0.0366) and Wong Baker FACES pain score plots (p = 0.0024). Cumulated morphine uses were not significantly decreased with Orthostat-L™. The addition of lidocaine to a hemostatic putty offers a significant ICBG donor site pain reduction over the first 12 postoperative hours. ClinicalTrials.gov NCT01504035. Registered January 2nd 2012.

Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: Using propensity score matching.

PubMed

Park, Jun Chul; Kim, Yeong Jin; Kim, Eun Hye; Lee, Jinae; Yang, Hyun Su; Kim, Eun Hwa; Hahn, Kyu Yeon; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan

2018-02-07

Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Normal Hemostatic Profiles and Coagulation Factors in Healthy Free-Living Florida Manatees ( Trichechus manatus latirostris).

PubMed

Barratclough, Ashley; Floyd, Ruth Francis; Conner, Bobbi; Reep, Roger; Ball, Ray; Stacy, Nicole

2016-10-01

Hemostatic disorders presumptively play an important role in the pathophysiology of several important disease conditions in the Florida manatee ( Trichechus manatus latirostris). Prior to pursuing such clinical implications, it is essential to establish normal hemostatic profiles in clinically healthy animals. During annual health assessments of free-living manatees organized by the US Geological Survey, blood samples were collected from 12 healthy animals from the Atlantic coast and 28 from the Gulf of Mexico coast of Florida, with body lengths of 210-324 cm. The following analyses were performed on citrated plasma: prothrombin (PT), partial thromboplastin time (PTT), and concentrations of fibrinogen, D-dimers, and coagulation factors VII, VIII, IX, X, XI, and XII. Compared to other mammalian species, manatees had short PT (9.2±1.5 s) and PTT (10.7±0.5 s), fibrinogen was 369±78.7 mg/dL, antithrombin III was 132±11%, and D-dimer was 142±122 ng/mL. Baseline concentrations for the listed coagulation factors were established. When comparing coagulation factors between locations, Atlantic coast manatees had significantly higher factors VIII, IX, and X than did Gulf Coast manatees. This finding may reflect differences in water salinity, diet, or genetics. There were no differences in coagulation factors when among sexes and sizes. These baselines for hemostatic profiles and coagulation factors in healthy free-living manatees lay the foundation for diagnosis and future research of hemostatic disorders and contribute to understanding their role in the pathophysiology of manatees affected by various diseases.

Pathways of fluid transport and reabsorption across the peritoneal membrane.

PubMed

Asghar, R B; Davies, S J

2008-05-01

The three-pore model of peritoneal fluid transport predicts that once the osmotic gradient has dissipated, fluid reabsorption will be due to a combination of small-pore reabsorption driven by the intravascular oncotic pressure, and an underlying disappearance of fluid from the cavity by lymphatic drainage. Our study measured fluid transport by these pathways in the presence and absence of an osmotic gradient. Paired hypertonic and standard glucose-dwell studies were performed using radio-iodinated serum albumin as an intraperitoneal volume marker and changes in intraperitoneal sodium mass to determine small-pore versus transcellular fluid transport. Disappearance of iodinated albumin was considered to indicate lymphatic drainage. Variability in transcellular ultrafiltration was largely explained by the rate of small-solute transport across the membrane. In the absence of an osmotic gradient, fluid reabsorption occurred via the small-pore pathway, the rate being proportional to the small-solute transport characteristics of the membrane. In most cases, fluid removal from the peritoneal cavity by this pathway was faster than by lymphatic drainage. Our study shows that the three-pore model describes the pathways of peritoneal fluid transport well. In the presence of high solute transport, poor transcellular ultrafiltration was due to loss of the osmotic gradient and an enhanced small-pore reabsorption rate after this gradient dissipated.

Hemostatic Agents in Periapical Surgery: A Randomized Study of Gauze Impregnated in Epinephrine versus Aluminum Chloride.

PubMed

Menéndez-Nieto, Isabel; Cervera-Ballester, Juan; Maestre-Ferrín, Laura; Blaya-Tárraga, Juan Antonio; Peñarrocha-Oltra, David; Peñarrocha-Diago, Miguel

2016-11-01

Adequate bleeding control is essential for the success of periapical surgery. The aim of this study was to evaluate the effects of 2 hemostatic agents on the outcome of periapical surgery and their relationship with patient and teeth parameters. A prospective study was designed with 2 randomized parallel groups, depending on the hemostatic agent used: gauze impregnated in epinephrine (epinephrine group) and aluminum chloride (aluminum chloride group). The analysis of the hemorrhage control was judged before and after the application of the hemostatic agents by the surgeon, and 2 examiners independently recorded it as adequate (complete hemorrhage control) or inadequate (incomplete hemorrhage control). Ninety-nine patients with a periradicular lesion were enrolled in this study and divided into 2 groups: gauze impregnated in epinephrine in 48 patients (epinephrine group) or aluminum chloride in 51 (aluminum chloride group). In epinephrine group adequate hemostasis was achieved in 25 cases, and in aluminum chloride group it was achieved in 37 cases (P < .05). The outcome was better in the aluminum chloride group than in the gauze impregnated in epinephrine group. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Osteogenic differentiation of preosteoblasts on a hemostatic gelatin sponge

PubMed Central

Kuo, Zong-Keng; Lai, Po-Liang; Toh, Elsie Khai-Woon; Weng, Cheng-Hsi; Tseng, Hsiang-Wen; Chang, Pei-Zen; Chen, Chih-Chen; Cheng, Chao-Min

2016-01-01

Bone tissue engineering provides many advantages for repairing skeletal defects. Although many different kinds of biomaterials have been used for bone tissue engineering, safety issues must be considered when using them in a clinical setting. In this study, we examined the effects of using a common clinical item, a hemostatic gelatin sponge, as a scaffold for bone tissue engineering. The use of such a clinically acceptable item may hasten the translational lag from laboratory to clinical studies. We performed both degradation and biocompatibility studies on the hemostatic gelatin sponge, and cultured preosteoblasts within the sponge scaffold to demonstrate its osteogenic differentiation potential. In degradation assays, the gelatin sponge demonstrated good stability after being immersed in PBS for 8 weeks (losing only about 10% of its net weight and about 54% decrease of mechanical strength), but pepsin and collagenases readily biodegraded it. The gelatin sponge demonstrated good biocompatibility to preosteoblasts as demonstrated by MTT assay, confocal microscopy, and scanning electron microscopy. Furthermore, osteogenic differentiation and the migration of preosteoblasts, elevated alkaline phosphatase activity, and in vitro mineralization were observed within the scaffold structure. Each of these results indicates that the hemostatic gelatin sponge is a suitable scaffold for bone tissue engineering. PMID:27616161

Hemostatic kaolin-polyurethane foam composites for multifunctional wound dressing applications.

PubMed

Lundin, Jeffrey G; McGann, Christopher L; Daniels, Grant C; Streifel, Benjamin C; Wynne, James H

2017-10-01

There are numerous challenges associated with the acute care of traumatic limb injuries in forward military settings. A lack of immediate medical facilities necessitates that the wound dressing perform multiple tasks including exudate control, infection prevention, and physical protection of the wound for extended periods of time. Here, kaolin was incorporated into recently developed robust polyurethane (PU) hydrogel foams at 1-10wt% in an effort to impart hemostatic character. ATR-IR and gel fraction analysis demonstrated that the facile, one-pot synthesis of the PU hydrogel was unaffected by kaolin loading, as well as the use of a non-toxic catalyst, which significantly improved cytocompatibility of the materials. Kaolin was generally well dispersed throughout the PU matrix, though higher loadings exhibited minor evidence of aggregation. Kaolin-PU composites exhibited burst release of ciprofloxacin over 2h, the initial release rates of which increased with kaolin loading. Kaolin loading imparted excellent hemostatic character to the PU foams at relatively low loading levels (5wt%). This work demonstrates the simple and inexpensive synthesis of robust, hemostatic, and absorptive kaolin-PU foams that have promising potential as multifunctional wound dressing materials. Published by Elsevier B.V.

In vivo degradation of polyurethane foam with 55 wt % polyethylene glycol.

PubMed

Broekema, Ferdinand I; Van Leeuwen, M Barbara M; Van Minnen, Baucke; Bos, Rudolf R M

2015-11-01

Most topical hemostatic agents are based on animal-derived products like collagen and gelatin. They carry the potential risk of pathogen transmission while adjustments in the production process of these materials are limited. A synthetic hemostatic agent based on polyurethane (PU) and polyethylene glycol (PEG) was developed to overcome these disadvantages. The goal of this study was to compare the degradation process of this biomaterial to collagen and gelatin hemostatic agents. Samples of the test materials were implanted subcutaneously in both rats and rabbits. The animals were sacrificed at certain time intervals up to three years and the explanted samples were microscopically assessed. The histological examination showed a comparable pattern of degradation for the different test materials. Remnants of gelatin and collagen were seen up to 26 and 39 weeks, respectively. For PU, it took up to three years before micro-particles of the material were no longer detected. All biomaterials showed a good biocompatibility and no severe foreign body reactions occurred. The good biocompatibility and predictable pattern of resorption indicate that PU can be used as a topical hemostatic agent. However, a degradation time comparable to collagen and gelatin would be favorable. © 2015 Wiley Periodicals, Inc.

Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism.

PubMed

Klipping, Christine; Marr, Joachim

2005-06-01

To compare the effect of ethinyl estradiol 20 microg/drospirenone 3 mg (EE 20 microg/DRSP 3 mg) administered according to a 24/4 regimen with ethinyl estradiol 20 microg/desogestrel 150 microg (EE 20 microg/DSG 150 microg) administered according to the conventional 21/7 regimen on lipid, carbohydrate and hemostatic parameters. In this open-label study, healthy women were randomized to EE 20 microg/DRSP 3 mg or EE 20 microg/DSG 150 microg for seven cycles. Mean differences in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels at cycle 7 compared to baseline were assessed. Secondary variables included changes in other lipid, hemostatic and carbohydrate parameters. Both treatments increased HDL-cholesterol, but decreased LDL-cholesterol by a comparable extent. Although slightly elevated in both groups, blood glucose and C-peptide levels measured during oral glucose tolerance tests were within normal reference ranges at cycle 7. Overall, the differences in lipid, hemostatic or carbohydrate parameters were not significant between the two treatments. EE 20 microg/DRSP 3 mg has a good safety profile comparable with EE 20 microg/DSG 150 microg.

Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

PubMed

Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

2012-06-01

Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.

Restrictive Versus Massive Fluid Resuscitation Strategy (REFILL study), influence on blood loss and hemostatic parameters in obstetric hemorrhage: study protocol for a randomized controlled trial.

PubMed

de Lange, Natascha; Schol, Pim; Lancé, Marcus; Woiski, Mallory; Langenveld, Josje; Rijnders, Robbert; Smits, Luc; Wassen, Martine; Henskens, Yvonne; Scheepers, Hubertina

2018-03-06

Postpartum hemorrhage (PPH) is associated with maternal morbidity and mortality and has an increasing incidence in high-resource countries, despite dissemination of guidelines, introduction of skills training, and correction for risk factors. Current guidelines advise the administration, as fluid resuscitation, of almost twice the amount of blood lost. This advice is not evidence-based and could potentially harm patients. All women attending the outpatient clinic who are eligible will be informed of the study; oral and written informed consent will be obtained. Where there is more than 500 ml blood loss and ongoing bleeding, patients will be randomized to care as usual, fluid resuscitation with 1.5-2 times the amount of blood loss or fluid resuscitation with 0.75-1.0 times the blood loss. Blood loss will be assessed by weighing all draping. A blood sample, for determining hemoglobin concentration, hematocrit, thrombocyte concentration, and conventional coagulation parameters will be taken at the start of the study, after 60 min, and 12-18 h after delivery. In a subgroup of women, additional thromboelastometric parameters will be obtained. Our hypothesis is that massive fluid administration might lead to a progression of bleeding due to secondary coagulation disorders. In non-pregnant individuals with massive blood loss, restrictive fluid management has been shown to prevent a progression to dilution coagulopathy. These data, however, cannot be extrapolated to women in labor. Our objective is to compare both resuscitation protocols in women with early, mild PPH (blood loss 500-750 ml) and ongoing bleeding, taking as primary outcome measure the progression to severe PPH (blood loss > 1000 ml). Netherlands Trial Register, NTR 3789 . Registered on 11 January 2013.

Local Anesthetic-Induced Neurotoxicity

PubMed Central

Verlinde, Mark; Hollmann, Markus W.; Stevens, Markus F.; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

2016-01-01

This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor. PMID:26959012

Local Anesthetic-Induced Neurotoxicity.

PubMed

Verlinde, Mark; Hollmann, Markus W; Stevens, Markus F; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

2016-03-04

This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor.

Natural Products with Antiplatelet Action.

PubMed

Hirsch, Gabriela Elisa; Viecili, Paulo Ricardo Nazario; de Almeida, Amanda Spring; Nascimento, Sabrina; Porto, Fernando Garcez; Otero, Juliana; Schmidt, Aline; da Silva, Brenda; Parisi, Mariana Migliorini; Klafke, Jonatas Zeni

2017-01-01

Complex hemostatic mechanisms are involved in the pathophysiology of various diseases, including cardiovascular diseases. Among them, dysregulation of platelet activity is linked to the progression of atherosclerosis and mainly involves platelet aggregation and a decrease in blood flow in the vascular endothelium. The major platelet activation pathways mediated by agonists involve the arachidonic acid pathway, adenosine diphosphate pathway, serotonin pathway, nitric oxide pathway, and action of free radicals on molecules involved in platelet aggregation. These mechanisms have been widely studied and discussed because they are inhibited by the use of medicinal plants in complementary and alternative medicine, thus reducing platelet aggregation. Of the main plants discussed in this review, which have antiplatelet activity, some include saffron, garlic, green tea, St. John's wort, ginger, ginkgo biloba, ginseng, and guavirova. These herbal medicines have phytochemical components, which are directly related to the antiplatelet activity of the plant, such as flavonoids, curcumins, catechins, terpenoids, polyphenols, and saponins. While the majority of the medicinal plants mentioned here were native to the Asian continents, some are distributed worldwide, and found to a smaller extent throughout the American continent, European continent, Mediterranean, African continent, and the Middle East. This review showed that several plants and/or compounds exhibit anti-platelet activity, and are therefore potential research targets for developing drugs to treat diseases related to aggregation disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vaccine Immunotherapy for Prostate Cancer. Addendum

DTIC Science & Technology

2007-07-01

a hemostatic agent. It is a water-insoluble, off-white, non- elastic, porous, pliable product prepared from purified pork skin. The Gelfoam gelatin ...increasing gelatin volume (27). PROTOCOL #1 Lubaroff; final addendum report, page 8 The mechanism of action of surface-mediated hemostatic devices is...and the clinical protocol. 3.2.14 Allergy or religious objection to pork products; Gelfoam is produced from pork. 4. Registration Procedures

Hemostatic agents and instruments in laparoscopic renal surgery.

PubMed

Msezane, Lambda P; Katz, Mark H; Gofrit, Ofer N; Shalhav, Arieh L; Zorn, Kevin C

2008-03-01

Control of bleeding is one of the most technically challenging steps in laparoscopic renal surgery, especially partial nephrectomy. Although there is no consensus on how best to approach hemostasis, the options continue to expand. The original method of sutured renorrhaphy is, perhaps, the most effective; however, great skill is needed to avoid prolonged warm ischemia. Tissue sealants and adhesives serve as a barrier to leakage and as a hemostat. The four classes are fibrin sealants, collagen-based adhesives, hydrogel, and glutaraldehyde-based adhesive. Additionally, oxidized cellulose can be applied to the surface of kidney or used as a bolster. Fibrin sealants are self-activating and work best on a dry field. The gelatin matrix agent consists of human-derived thrombin with a calcium chloride solution and bovine-derived gelatin matrix. The fibrinogen required to form a clot comes from autologous blood. Another product is polyethylene glycol-based hydrogel, which acts as a mechanical sealant. The tissue glue consists of bovine serum albumin and glutaraldehyde, which cross-link to each other, as well as to other tissue proteins. Excessive use or spillage around the renal pelvis and ureter may compromise urinary flow. The methylcellulose products, consisting of oxidized cellulose sheets, usually are positioned within a sutured bolster and act in part by providing direct pressure. A number of energy-based technologies also have been utilized. Monopolar cautery consists of a high-frequency electrical current delivered from a single electrode. Care must be taken to avoid injurious current transfer to surrounding structures. With bipolar cautery, hemostasis occurs only between the electrodes. In the argonbeam coagulator, argon, an inert non-flammable gas that clears from the body rapidly, is coupled with an electrosurgical generator. The gas creates a more even distribution of the energy and better sealing of the tissues. There have been a few reports of serious complications, including gas embolism and tension pneumothorax. The holmium:YAG laser simultaneously dissects and coagulates tissue. However, its use may be limited by smoke and by blood splashing onto the camera lens, and the tissue vaporization and liquid could promote tumor-cell spillage. The potassium-titanyl-phosphate (KTP) and diode lasers have shown promise in animal studies. The saline-coupled radiofrequency tool uses a standard electrosurgical generator to deliver energy through the conductive fluid. The fluid keeps the surface temperature much lower, increases the contact area, and reduces char and eschar formation. One caveat for the use of instruments that coagulate and ablate tissue is that they can damage the collecting system. Furthermore, the char can make it difficult to assess margin status. In practice, a combination of instruments, sealants, or both generally is utilized to obtain hemostasis. These multimodality efforts may be especially useful in the patient with compromised renal function. On the other hand, the cost can rise quickly when multiple agents are employed. Combining suturing and hemostatic technology may be the best strategy.

Hemostatic findings of pleural fluid in dogs and the association between pleural effusions and primary hyperfibrino(geno)lysis: A cohort study of 99 dogs

PubMed Central

Drigo, Michele; Piek, Christine J.; Simioni, Paolo; Caldin, Marco

2018-01-01

The primary objective of this study was to determine if activation of coagulation and fibrinolysis occurs in canine pleural effusions. Thirty-three dogs with pleural effusions of different origin were studied. Pleural effusion fibrinogen concentrations were significantly lower, while pleural fibrin-fibrinogen degradation products (FDPs) and D-dimer concentrations were significantly higher than those in plasma (P < 0.001 for all comparisons). These results show that, in canine pleural fluids, there is evidence of coagulation activation and fibrinolysis. The secondary aims of the current study were to determine if primary hyperfibrinolysis ([PHF] i.e., elevated plasma FDPs with a normal D-dimer concentrations), occurs in dogs with pleural effusion, and whether the presence of a concurrent inflammatory process may have activated the hemostatic cascade, with its intrinsically linked secondary hyperfibrinolysis, masking the concurrent PHF. The previously 33 selected dogs with pleural effusion (group 1) were compared to two control groups of 33 healthy (group 2) and 33 sick dogs without pleural effusion (group 3). Serum fibrinogen, FDPs, D-dimer, C-reactive protein (CRP), fibrinogen/CRP ratio, and frequency of PHF were determined. Fibrinogen, FDPs, D-dimer and CRP concentrations in group 1 were significantly increased compared to group 2 (P < 0.001 for all comparisons). FDPs and CRP concentrations in group 1 were also significantly increased compared to group 3 (P = 0.001 and P < 0.001, respectively). The fibrinogen/CRP ratio was significantly decreased in group 1 compared to groups 2 and 3 (P < 0.001 for both comparison). The frequency of PHF was significantly higher in group 1 compared to groups 2 (P = 0.004), but not compared to group 3. These results support the hypothesis that PHF occurs significantly more often in dogs with pleural effusion compared to healthy dogs. Nevertheless, the decrease in the fibrinogen/CRP ratio in group 1 compared to group 3, considering the higher FDPs and similar D-dimer concentrations, would suggest that PHF is also more frequent in dogs with pleural effusion compared to sick control dogs, and that this phenomenon is hidden due to concurrent secondary hyperfibrinolysis. PMID:29462172

Hemostatic findings of pleural fluid in dogs and the association between pleural effusions and primary hyperfibrino(geno)lysis: A cohort study of 99 dogs.

PubMed

Zoia, Andrea; Drigo, Michele; Piek, Christine J; Simioni, Paolo; Caldin, Marco

2018-01-01

The primary objective of this study was to determine if activation of coagulation and fibrinolysis occurs in canine pleural effusions. Thirty-three dogs with pleural effusions of different origin were studied. Pleural effusion fibrinogen concentrations were significantly lower, while pleural fibrin-fibrinogen degradation products (FDPs) and D-dimer concentrations were significantly higher than those in plasma (P < 0.001 for all comparisons). These results show that, in canine pleural fluids, there is evidence of coagulation activation and fibrinolysis. The secondary aims of the current study were to determine if primary hyperfibrinolysis ([PHF] i.e., elevated plasma FDPs with a normal D-dimer concentrations), occurs in dogs with pleural effusion, and whether the presence of a concurrent inflammatory process may have activated the hemostatic cascade, with its intrinsically linked secondary hyperfibrinolysis, masking the concurrent PHF. The previously 33 selected dogs with pleural effusion (group 1) were compared to two control groups of 33 healthy (group 2) and 33 sick dogs without pleural effusion (group 3). Serum fibrinogen, FDPs, D-dimer, C-reactive protein (CRP), fibrinogen/CRP ratio, and frequency of PHF were determined. Fibrinogen, FDPs, D-dimer and CRP concentrations in group 1 were significantly increased compared to group 2 (P < 0.001 for all comparisons). FDPs and CRP concentrations in group 1 were also significantly increased compared to group 3 (P = 0.001 and P < 0.001, respectively). The fibrinogen/CRP ratio was significantly decreased in group 1 compared to groups 2 and 3 (P < 0.001 for both comparison). The frequency of PHF was significantly higher in group 1 compared to groups 2 (P = 0.004), but not compared to group 3. These results support the hypothesis that PHF occurs significantly more often in dogs with pleural effusion compared to healthy dogs. Nevertheless, the decrease in the fibrinogen/CRP ratio in group 1 compared to group 3, considering the higher FDPs and similar D-dimer concentrations, would suggest that PHF is also more frequent in dogs with pleural effusion compared to sick control dogs, and that this phenomenon is hidden due to concurrent secondary hyperfibrinolysis.

Interventions for treating acute bleeding episodes in people with acquired hemophilia A.

PubMed

Zeng, Yan; Zhou, Ruiqing; Duan, Xin; Long, Dan; Yang, Songtao

2014-08-28

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). In most cases, bleeding episodes are spontaneous and severe at presentation. The optimal hemostatic therapy is controversial. To determine the efficacy of hemostatic therapies for acute bleeds in people with acquired hemophilia A; and to compare different forms of therapy for these bleeds. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 4) and MEDLINE (Ovid) (1948 to 30 April 2014). We searched the conference proceedings of the: American Society of Hematology; European Hematology Association; International Society on Thrombosis and Haemostasis (ISTH); and the European Association for Haemophilia and Allied Disorders (EAHAD) (from 2000 to 30 April 2014). In addition to this we searched clinical trials registers. All randomised controlled trials and quasi-randomised trials of hemostatic therapies for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. No randomised clinical trials of hemostatic therapies for acquired hemophilia A were found. Thus, we are not able to draw any conclusions or make any recommendations on the optimal hemostatic therapies for acquired hemophilia A based on the highest quality of evidence. GIven that carrying out randomized controlled trials in this field is a complex task, the authors suggest that, while planning randomised controlled trials in which patients can be enrolled, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence, which hopefully, in the future, will also be appraised and incorporated in a Cochrane Review.

Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.

PubMed

Smith, Ann; Patterson, Chris; Yarnell, John; Rumley, Ann; Ben-Shlomo, Yoav; Lowe, Gordon

2005-11-15

Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors. A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI-1 were significantly associated with risk of CVD, whereas factor VIIc showed an inverse association (P=0.001). In a model that contained the conventional risk factors, the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD. This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors. Fibrinogen, D-dimer, PAI-1 activity, and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men, in addition to conventional risk factors.

Stent-Grafts in the Management of Hemorrhagic Complications Related to Hemostatic Closure Devices: Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giansante Abud, Daniel; Mounayer, Charbel; Saint-Maurice, Jean Pierre

We report 2 cases of hemorrhagic complications related to use of the Angio-Seal hemostatic closure device that were successfully managed with stent-grafts. Two patients with subarachnoid hemorrhage were referred to our departments for endovascular treatment of ruptured intracranial aneurysms. The treatment was performed through a femoral access; the sheaths were removed immediately after the procedures, and the punctures sites closed by Angio-Seals. Both patients presented clinical signs of hypovolemic shock after treatment. The diagnosis of active bleeding through the puncture site was made by emergency digital subtraction angiography. The lesions were managed with stent-grafts. The use of stent-grafts proved tomore » be efficient in the management of these life-threatening hemorrhagic complications following the use of the Angio-Seal hemostatic closure device.« less

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

PubMed

Günther, A; Mosavi, P; Ruppert, C; Heinemann, S; Temmesfeld, B; Velcovsky, H G; Morr, H; Grimminger, F; Walmrath, D; Seeger, W

2000-06-01

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

Evaluation of FloSeal as a Potential Intracavitary Hemostatic Agent

DTIC Science & Technology

2006-02-01

Laws ER Jr. Use of FloSeal hemostatic sealant in transsphenoidal pituitary surgery : technical note. Neurosurgery. 2002;51:513–516. 14. Kheirabadi BS...of death in com- bat and civilian trauma. When surgery is unavailable, one potential solution to such hemorrhage might be the introduction of an agent...situations, including venous and arterial vascular surgery ,7,9 cardiac valve replacement or cardiopulmonary bypass grafting,6 partial nephrectomies,10

Colonoscopic findings and management of patients with outbreak typhoid fever presenting with lower gastrointestinal bleeding.

PubMed

Shaikhani, Mohammad A R; Husein, Hiwa A B; Karbuli, Taha A; Mohamed, Mohamed Abdulrahman

2013-09-01

Lower gastrointestinal bleeding (LGIB) along with intestinal perforation is a well-known complication of typhoid fever. Reports of colonoscopic appearance and intervention of typhoid perforation involve only few cases. This series reports the colonoscopic findings and the role of colonoscopic hemostatic interventions in controlling the bleeding ileocolonic lesions. During the typhoid fever outbreak in Sulaymaniyah City in Iraqi Kurdistan Region, we received 52 patients with LGIB manifesting as fresh bleeding per rectum or melena. We performed total colonoscopy with ileal intubation for all cases. The findings were recorded and endoscopic hemostatic intervention with adrenaline-saline injection and argon plasma coagulation was applied to actively bleeding lesion. These patients were young, 11-30 years of age, with female preponderance. Blood culture was positive in 50 %. Colonoscopic findings were mostly located in the ileocecal region, although other areas of the colon were involved in many cases. Twenty-four percent of the cases required endoscopic hemostatic intervention by adrenaline injection with argon plasma coagulation which was effective in all patients except one who died in spite of surgical intervention in addition of endoscopic hemostasis. Dual endoscopic hemostatic intervention can be a safe and effective management option for patients with LGIB due to typhoid fever.

The Design and Testing of a Dual Fiber Textile Matrix for Accelerating Surface Hemostasis

PubMed Central

Fischer, Thomas H.; Vournakis, John N.; Manning, James E.; McCurdy, Shane L.; Rich, Preston B.; Nichols, Timothy C.; Scull, Christopher M.; McCord, Marian G.; Decorta, Joseph A.; Johnson, Peter C.; Smith, Carr J.

2011-01-01

The standard treatment for severe traumatic injury is frequently compression and application of gauze dressing to the site of hemorrhage. However, while able to rapidly absorb pools of shed blood, gauze fails to provide strong surface (topical) hemostasis. The result can be excess hemorrhage-related morbidity and mortality. We hypothesized that cost-effective materials (based on widespread availability of bulk fibers for other commercial uses) could be designed based on fundamental hemostatic principles to partially emulate the wicking properties of gauze while concurrently stimulating superior hemostasis. A panel of readily available textile fibers was screened for the ability to activate platelets and the intrinsic coagulation cascade in vitro. Type E continuous filament glass and a specialty rayon fiber were identified from the material panel as accelerators of hemostatic reactions and were custom woven to produce a dual fiber textile bandage. The glass component strongly activated platelets while the specialty rayon agglutinated red blood cells. In comparison with gauze in vitro, the dual fiber textile significantly enhanced the rate of thrombin generation, clot generation as measured by thromboelastography, adhesive protein adsorption and cellular attachment and activation. These results indicate that hemostatic textiles can be designed that mimic gauze in form but surpass gauze in ability to accelerate hemostatic reactions. PMID:19489008

Fibrin Sealant: The Only Approved Hemostat, Sealant, and Adhesive—a Laboratory and Clinical Perspective

PubMed Central

Spotnitz, William D.

2014-01-01

Background. Fibrin sealant became the first modern era material approved as a hemostat in the United States in 1998. It is the only agent presently approved as a hemostat, sealant, and adhesive by the Food and Drug Administration (FDA). The product is now supplied as patches in addition to the original liquid formulations. Both laboratory and clinical uses of fibrin sealant continue to grow. The new literature on this material also continues to proliferate rapidly (approximately 200 papers/year). Methods. An overview of current fibrin sealant products and their approved uses and a comprehensive PubMed based review of the recent literature (February 2012, through March 2013) on the laboratory and clinical use of fibrin sealant are provided. Product information is organized into sections based on a classification system for commercially available materials. Publications are presented in sections based on both laboratory research and clinical topics are listed in order of decreasing frequency. Results. Fibrin sealant remains useful hemostat, sealant, and adhesive. New formulations and applications continue to be developed. Conclusions. This agent remains clinically important with the recent introduction of new commercially available products. Fibrin sealant has multiple new uses that should result in further improvements in patient care. PMID:24729902

Radial hemostasis is facilitated with a potassium ferrate hemostatic patch: the Statseal with TR band assessment trial (STAT).

PubMed

Seto, Arnold H; Rollefson, William; Patel, Mitul P; Suh, William M; Tehrani, David M; Nguyen, Jacqueline A; Amador, Daniel G; Behnamfar, Omid; Garg, Vinisha; Cohen, Mauricio G

2018-05-15

Hemostasis is a limiting factor for discharge after uncomplicated transradial procedures. The potassium ferrate hemostatic patch (PFHP) may serve as an adjunct to the air-bladder TR band (TRB) and allow expedited deflation of the TRB. Prospective multicenter randomized controlled trial comparing radial hemostatic protocols. Deflation of the TRB was attempted at 40 minutes with PFHP and at 120 minutes without the PFHP. The primary outcome was time to full deflation of the TRB with hemostasis. At four U.S. sites, 180 patients were enrolled after receiving a minimum of 5,000 units of unfractionated heparin or bivalirudin. Interventions comprised 30% of procedures. Successful TRB deflation occurred at 43 ± 14 minutes with PFHP and 160 ± 43 minutes without PFHP (p<0.001). Minor hematomas occurred in 9 (10.3%) of TRB patients and 16 (17.2%) of PFHP patients (p=0.20). Radial artery occlusion occurred in 2% of patients in the PFHP group (p=NS). Outpatients randomized to PFHP were discharged 51 ± 83.5 minutes earlier than control. The PFHP hemostatic patch facilitated early deflation of the TRB with a nonsignificant increase in forearm hematomas. Use of the PFHP may improve patient throughput and allow for earlier discharge following transradial procedures.

Contemporary review of the 532 nm laser for treatment of benign prostatic hyperplasia.

PubMed

Chughtai, Bilal; Laor, Leanna; Dunphy, Claire; Te, Alexis

2015-04-01

Benign prostatic hyperplasia (BPH) is a condition that occurs increasingly with age. The established gold standard treatment for BPH has been the electrocautery-based transurethral resection of the prostate (TURP). TURP, however, is associated with several complications and side effects. Therefore, there is an increasing interest in a number of emerging minimally invasive therapies as alterative treatment options. Laser therapy using the Greenlight laser is a promising alternative to the traditional TURP. Selective absorption by hemoglobin allows rapid, hemostatic vaporization of prostate tissue. Additional advantages include avoidance or minimization of complications such as intraoperative fluid absorption, and bleeding, retrograde ejaculation, impotence, and incontinence, as well as its use in treating high volume BPH. We review the use of the Greenlight laser in the treatment of BPH, when comparing complications and advantages in relation to TURP.

Mechanobiology of Platelets: Techniques to Study the Role of Fluid Flow and Platelet Retraction Forces at the Micro- and Nano-Scale

PubMed Central

Feghhi, Shirin; Sniadecki, Nathan J.

2011-01-01

Coagulation involves a complex set of events that are important in maintaining hemostasis. Biochemical interactions are classically known to regulate the hemostatic process, but recent evidence has revealed that mechanical interactions between platelets and their surroundings can also play a substantial role. Investigations into platelet mechanobiology have been challenging however, due to the small dimensions of platelets and their glycoprotein receptors. Platelet researchers have recently turned to microfabricated devices to control these physical, nanometer-scale interactions with a higher degree of precision. These approaches have enabled exciting, new insights into the molecular and biomechanical factors that affect platelets in clot formation. In this review, we highlight the new tools used to understand platelet mechanobiology and the roles of adhesion, shear flow, and retraction forces in clot formation. PMID:22272117

Development of a Standard Swine Hemorrhage Model for Efficacy Assessment of Topical Hemostatic Agents

DTIC Science & Technology

2011-07-01

Blw:kbourne. MD Background: The diverse infomlation of efficacy of hemostatic pmducts. obtained from different military laboratories using ...model was tested with all or some of these modifications in four experimental conditions (n = 5-6 pigs pc:r condition) using Combat Gauze (CG) as...be suitable lf.>r testing every agent and some modifications may be necessary for specific applications. fu•·thermore, laboratory studies using this

Comparison of 10 Hemostatic Dressings in a Groin Puncture Model in Swine

DTIC Science & Technology

2009-09-01

attended or remote surgical theaters as well as for first aid bandaging in extreme sport.Methods to suppress massive external hemorrhage should be provided...Products Newport, O Instaclot (IC) Emergency Medical Devices Loxa WoundStat (WS) TraumaCure, Inc. Bethesda, Md Solid (flexible) agents Alpha Bandage ...referred to throughout are listed in Table I. The hemostatic products and the standard compressed gauze bandage (SD; H&H compressed gauze, H&H

Fibrin glue as a hemostatic agent in hepatic and splenic trauma.

PubMed

Ochsner, M G; Maniscalco-Theberge, M E; Champion, H R

1990-07-01

Fibrin glue is a biologic hemostatic agent that coagulates and seals upon application. It is made by combining human fibrinogen concentrate with standard thrombin solutions containing calcium. Similar to epoxy glue, the two components are applied simultaneously in equal volumes resulting in an almost instantaneous formation of a coagulum. Fibrinogen concentrate is prepared in the blood bank from single donor plasma. Fibrin glue can be applied topically or injected into the parenchyma of solid organs. Twenty-six patients sustained hepatic or splenic trauma from May through August 1989--17 liver and nine splenic injuries. The glue was effective after one application in 21 patients and after a second in five. Hemostasis was achieved despite coagulopathy and thrombocytopenia in eight patients. There were no re-explorations for bleeding, and nine complications occurred in six patients. Our experience suggests fibrin glue is an effective, underutilized adjunctive hemostatic agent in trauma.

[Change in Perioperative Hemostatic Function in Patients Undergoing Hepatic Resection for Primary and Metastatic Liver Cancer].

PubMed

Komasawa, Nobuyasu; Ueki, Ryusuke; Atagi, Kazuaki; Nishi, Shinichi

2015-08-01

Patients undergoing primary hepatic resection often develop hemostatic dysfunction associated with cirrhosis. We retrospectively surveyed pre- and postoperative prothrombin time (PT) and the PT expressed as international normalized ratio (PT-INR) in 39 patients undergoing primary liver resection. We also compared PT changes between primary and metastatic cancer cases (8 cases). Postoperative PT-INR was 1.40 ± 0.38, which was significantly prolonged compared to preoperative PT-INR of 1.08 ± 0.07. Preoperative PT was over 70% in all 39 patients undergoing primary liver resection, whereas postoperative PT was less than 60% in 13 of 39 patients. No significant difference was found in preoperative PT-INR between primary and metastatic cancer cases, but postoperative PT-INR was significantly prolonged in primary cancer cases. Patients undergoing primary liver resection are susceptible to hemostatic dysfunction, even with preoperative PT levels within normal limits.

Robotic surgery and hemostatic agents in partial nephrectomy: a high rate of success without vascular clamping.

PubMed

Morelli, Luca; Morelli, John; Palmeri, Matteo; D'Isidoro, Cristiano; Kauffmann, Emanuele Federico; Tartaglia, Dario; Caprili, Giovanni; Pisano, Roberta; Guadagni, Simone; Di Franco, Gregorio; Di Candio, Giulio; Mosca, Franco

2015-09-01

Robot-assisted partial nephrectomy has been proposed as a technique to overcome technical challenges of laparoscopic partial nephrectomy. We prospectively collected and analyzed data from 31 patients who underwent robotic partial nephrectomy with systematic use of hemostatic agents, between February 2009 and October 2014. Thirty-three renal tumors were treated in 31 patients. There were no conversions to open surgery, intraoperative complications, or blood transfusions. The mean size of the resected tumors was 27 mm (median 20 mm, range 5-40 mm). Twenty-seven of 33 lesions (82%) did not require vascular clamping and therefore were treated in the absence of ischemia. All margins were negative. The high partial nephrectomy success rate without vascular clamping suggests that robotic nephron-sparing surgery with systematic use of hemostatic agents may be a safe, effective method to completely avoid ischemia in the treatment of selected renal masses.

Hemostasis and malignancy.

PubMed

Francis, J L; Biggerstaff, J; Amirkhosravi, A

1998-01-01

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

One amino acid in mouse activated factor VII defines its endothelial protein C receptor (EPCR) binding and modulates its EPCR-dependent hemostatic activity in vivo.

PubMed

Pavani, G; Zintner, S M; Ivanciu, L; Small, J C; Stafford, K A; Szeto, J H; Margaritis, P

2017-03-01

Essentials The lack of factor (F) VIIa-endothelial protein C receptor (EPCR) binding in mice is unresolved. A single substitution of Leu4 to Phe in mouse FVIIa (mFVIIa) enables its interaction with EPCR. mFVIIa with a Phe4 shows EPCR binding-dependent enhanced hemostatic function in vivo vs. mFVIIa. Defining the FVIIa-EPCR interaction in mice allows for further investigating its biology in vivo. Background Human activated factor VII (hFVIIa), which is used in hemophilia treatment, binds to the endothelial protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the activated FVII (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) by using three substitutions from mouse PC (mPC), i.e. Leu4→Phe, Leu8→Met, and Trp9→Arg. The resulting molecule, mFVIIa-FMR, modeled the EPCR-binding properties of hFVIIa and showed enhanced hemostatic capacity in hemophilic mice versus mFVIIa. These data implied a role of EPCR in the action of hFVIIa in hemophilia treatment. However, the substitutions in mFVIIa-FMR only broadly defined the sequence determinants for its mEPCR interaction and enhanced function in vivo. Objectives To determine the individual contributions of mPC Phe4, Met8 and Arg9 to the in vitro/in vivo properties of mFVIIa-FMR. Methods The mEPCR-binding properties of single amino acid variants of mFVIIa or mPC at position 4, 8 or 9 were investigated. Results and conclusions Phe4 in mFVIIa or mPC was solely critical for interaction with mEPCR. In hemophilic mice, administration of mFVIIa harboring a Phe4 resulted in a 1.9-2.5-fold increased hemostatic capacity versus mFVIIa that was EPCR binding-dependent. This recapitulated previous observations made with triple-mutant mFVIIa-FMR. As Leu8 is crucial for hFVIIa-EPCR binding, we describe the sequence divergence of this interaction in mice, now allowing its further characterization in vivo. We also illustrate that modulation of the EPCR-FVIIa interaction may lead to improved FVIIa therapeutics. © 2016 International Society on Thrombosis and Haemostasis.

Comparative Testing of New Hemostatic Agents in a Swine Model of Extremity Arterial and Venous Hemorrhage

DTIC Science & Technology

2010-01-01

by the Institutional Animal Care and Use Committee and all animals received humane care in com- pliance with the Guide for the Care and Use of...diminished markedly in recent military operations, due to sev- eral factors including routine vi-ear of hody armor, judicious use of tourniquets for...extremity hemorrhage, rapid casualty evacuation, and aggressive use of blood products in hemor- rhagic shock.’’ Advanced hemostatic agents further reduce

Self-Expanding, Tough Biodegradable Elastomers for Wound Stasis

DTIC Science & Technology

2015-08-06

results were incon- clusive in mixed (arterial and venous)17 and arterial bleed- ing.18,19 Likewise, QuikClot Zeolite granules were effective in venous...177Y182. 17. Alam HB, Chen Z, Jaskille A, et al. Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin...reactions of hemostatic agents, such as early- generation granular zeolite , have resulted in patient injury.20,21 In this study, the reaction between

Intraoperative anaphylaxis to gelatin in topical hemostatic agents during anterior spinal fusion: a case report.

PubMed

Spencer, Hillard T; Hsu, Joyce T; McDonald, Douglas R; Karlin, Lawrence I

2012-08-01

The use of topical hemostatic agents is widespread and has been shown to reduce bleeding during a wide variety of surgical procedures. Nonetheless, as biologically active agents, there is potential for allergic reactions to these products. This is a report of intraoperative anaphylaxis to gelatin associated with the use of two topical hemostatic agents. Case report. There is no outside funding or potential conflict of interest. A patient with anaphylaxis during anterior spinal fusion. Laboratory assays for tryptase, gelatin-specific immunoglobulin E (IgE), and total IgE. A 14-year-old male with myelomeningocele and scoliosis was treated with anterior spinal fusion from T12 to L3. Gelfoam sponges were applied during the preparation of the disc spaces. Approximately 1 hour later, Floseal hemostatic matrix was applied to a briskly bleeding screw hole in the L3 vertebral body, and the patient experienced an abrupt onset of hypotension and ventilatory difficulty. Epinephrine, dexamethasone, and blood products were administered for hemodynamic support while the surgical site was closed. Removal of the drapes revealed a widespread erythematous rash, and the patient was then transferred to the intensive care unit. When stable 3 days later, he returned to the operating room for completion of the spinal fusion. Postoperative laboratory assays were sent that revealed elevated levels of tryptase, total IgE, porcine, and bovine gelatin-specific IgE. The patient was counseled to avoid gelatin-containing products. At 6-month follow-up, his instrumented spine was radiographically fused and he reported no further allergic issues. Anaphylaxis may occur because of animal gelatin components of topical hemostatic agents. Previous reports have focused on the thrombin components. Care should be taken in the administration of these products, particularly in the atopic individual. Copyright © 2012 Elsevier Inc. All rights reserved.

3D seismic detection of shallow faults and fluid migration pathways offshore Southern Costa Rica: Application of neural-network meta-attributes

NASA Astrophysics Data System (ADS)

Kluesner, J. W.; Silver, E. A.; Nale, S. M.; Bangs, N. L.; McIntosh, K. D.

2013-12-01

We employ a seismic meta-attribute workflow to detect and analyze probable faults and fluid-pathways in 3D within the sedimentary section offshore Southern Costa Rica. During the CRISP seismic survey in 2011 we collected an 11 x 55 km grid of 3D seismic reflection data and high-resolvability EM122 multibeam data, with coverage extending from the incoming plate to the outer-shelf. We mapped numerous seafloor seep indicators, with distributions ranging from the lower-slope to ~15 km landward of the shelf break [Kluesner et al., 2013, G3, doi:10.1002/ggge.20058; Silver et al., this meeting]. We used the OpendTect software package to calculate meta-attribute volumes from the 3D seismic data in order to detect and visualize seismic discontinuities in 3D. This methodology consists of dip-steered filtering to pre-condition the data, followed by combining a set of advanced dip-steered seismic attributes into a single object probability attribute using a user-trained neural-network pattern-recognition algorithm. The parameters of the advanced seismic attributes are set for optimal detection of the desired geologic discontinuity (e.g. faults or fluid-pathways). The product is a measure of probability for the desired target that ranges between 0 and 1, with 1 representing the highest probability. Within the sedimentary section of the CRISP survey the results indicate focused fluid-migration pathways along dense networks of intersecting normal faults with approximately N-S and E-W trends. This pattern extends from the middle slope to the outer-shelf region. Dense clusters of fluid-migration pathways are located above basement highs and deeply rooted reverse faults [see Bangs et al., this meeting], including a dense zone of fluid-pathways imaged below IODP Site U1413. In addition, fault intersections frequently show an increased signal of fluid-migration and these zones may act as major conduits for fluid-flow through the sedimentary cover. Imaged fluid pathways root into high-backscatter pockmarks and mounds on the seafloor, which are located atop folds and clustered along intersecting fault planes. Combining the fault and fluid-pathway attribute volumes reveals qualitative first order information on fault seal integrity within the CRISP survey region, highlighting which faults and/or fault sections appear to be sealing or leaking within the sedimentary section. These results provide 3D insight into the fluid-flow behavior offshore southern Costa Rica and suggest that fluids escaping through the deeper crustal rocks are predominantly channeled along faults in the sedimentary cover, especially at fault intersections.

Toxicity of Aluminum Silicates Used in Hemostatic Dressings Toward Human Umbilical Veins Endothelial Cells, HeLa Cells, and RAW267.4 Mouse Macrophages

DTIC Science & Technology

2011-09-01

ORIGINAL ARTICLE Toxicity of Aluminum Silicates Used in Hemostatic Dressings Toward Human Umbilical Veins Endothelial Cells, HeLa Cells, and RAW267.4...not known. Clay minerals are generally considered nontoxic to humans and have been widely used in cosmetics and as excipient in drugs and foods...Bentonite, which has a long history in pharmaceutical formulations,7 along with kaolin are listed in the US Pharmacopeia.8 The sensitivity of some human

Extraterrestrial Hemorrhage Control: Terrestrial Developments in Technique, Technology, and Philosophy with Applicability to Traumatic Hemorrhage in Space

NASA Technical Reports Server (NTRS)

Kirkpatrick, Andrew; Dawson, David; Campbell, Mark; Jones, Jeff; Ball, Chad G.; Hamilton, Douglas R.; Dulchavsky, Scott; McBeth, Paul; Holcomb, John

2004-01-01

Managing injury and illness during long duration space flight limits efforts to explore beyond low earths orbit. Traumatic injury may be expected to occur in space and is a frequent cause of preventable deaths, often related to uncontrolled or ongoing hemorrhage (H). Such bleeding causes 40% of terrestrial injury mortality. Current guidelines emphasize early control of H compared to intravenous infusions. Recent advances in surgical and critical care may be applicable to trauma care in space, with appropriate considerations of the extreme logistical and personnel limitations. Methods: Recent developments in technique, resuscitation fluids, hemoglobin (Hb) substitutes, hemostatic agents, interventional angiography, damage control principles, and concepts related to suspended animation were reviewed. Results: H associated with instability frequently requires definitive intervention. Direct pressure should be applied to all compressible bleeding, but novel approaches are required for intracavitary noncompressible bleeding. Intravenous hemostatic agents such as recombinant Factor VII may facilitate hemostasis especially when combined with a controlled hypotension approach. Both open and laparoscopic techniques could be used in weightlessness, but require technical expertise not likely to be available. Specific rehearsed invasive techniques such as laparotomy with packing, or arterial catherterization with with robotic intravascular embolization might be considered . Hemodynamic support, thermal manipulation, or pharmacologic induction of a state of metabolic down regulation for whole body preservation may be appropriate. Hypertonic saline, with or without dextran, may temporize vascular support and decrease reperfusion injury, with less mass than other solutions. Hb substitutes have other theoretical advantages. Conclusions: Terrestrial developments suggest potential novel strategies to control H in space, but will required a coordinated program of evaluation and training to evaluate.

Inner Mitochondrial Membrane Disruption Links Apoptotic and Agonist-Initiated Phosphatidylserine Externalization in Platelets.

PubMed

Choo, Hyo-Jung; Kholmukhamedov, Andaleb; Zhou, ChengZing; Jobe, Shawn

2017-08-01

Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo. Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption. In both ABT-737 (apoptotic) and agonist (necrotic)-treated platelets, phosphatidylserine externalization was temporally correlated with IMM disruption. Agonist stimulation resulted in rapid cyclophilin D-dependent IMM disruption that coincided with phosphatidylserine exposure. ABT-737 treatment caused rapid cytochrome c release, eventually followed by caspase-dependent IMM disruption that again closely coincided with phosphatidylserine exposure. A nonmitochondrial and integrin-mediated mechanism has been implicated in the formation of a novel phosphatidylserine-externalizing platelet subpopulation. Using image cytometry, this subpopulation is demonstrated to be the result of the interaction of an aggregatory platelet and a procoagulant platelet rather than indicative of a novel intracellular mechanism regulating platelet phosphatidylserine externalization. Using electron microscopy, similar interactions between aggregatory and procoagulant platelets are demonstrated in vitro and in vivo within a mesenteric vein hemostatic thrombus. Platelet phosphatidylserine externalization is closely associated with the mitochondrial event of IMM disruption identifying a common pathway in phosphatidylserine-externalizing platelets. The limited interaction of procoagulant platelets and integrin-active aggregatory platelets identifies a potential mechanism for procoagulant platelet retention within the hemostatic thrombus. © 2017 American Heart Association, Inc.

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

PubMed

Lee, D; Nayak, S; Martin, S W; Heatherington, A C; Vicini, P; Hua, F

2016-12-01

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. Background Prothrombin fragment 1 + 2 (F 1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F 1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F 1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F 1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F 1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F 1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. © 2016 International Society on Thrombosis and Haemostasis.

Management of tooth extraction in a patient with a rare bleeding disorder associated with Hermansky-Pudlak syndrome: a case report.

PubMed

Minkin, Patton; Bertetti, Richard; Lindsey, Sean; Bovino, Brian

2015-02-01

This report describes the case of a 27-year-old man who had been diagnosed with Hermansky-Pudlak syndrome shortly after birth. Because the patient had a major bleeding disorder associated with his syndrome, local and systemic hemostatic protection recommendations had to be considered before tooth extraction. Synthetic vasopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) was transfused intravenously before surgery. During surgery the patient was transfused with 1 U of human leukocyte antigen (HLA)-matched apheresis platelets. A hemostatic packing of Avitene and Gelfoam was adapted to the extraction site. Treatment with DDAVP, HLA-matched platelets, and local application of a packing with Avitene and Gelfoam resulted in sustained hemostasis and an excellent healing response. Surgical and routine extractions appear to be safe procedures in patients with Hermansky-Pudlak syndrome when appropriate local and systemic hemostatic measures are used. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

[Use of "NovoSeven" (rFVIIa) hemostatic in patients operated with extracorporeal blood circulation].

PubMed

Dement'eva, I I; Sandrikov, V A; Charnaia, M A; Morozov, Iu A; Trekova, N A; Eremenko, A A

2004-01-01

The "NovoSeven" drug was used in 25 patients (male - 18, female - 7) operated on the heart and main vessels including with artificial extracorporeal circulation (AEC). Patients did not have any clinically significant impairment in blood circulation before surgery. Perioperatively, all of them and, immediately after surgery, 4 them had uncontrollable hemorrhages at 10-25 ml/min in spite of extensive hemostatic therapy, including freshly frozen plasma, cryoprecipitate, thromboconcentrate, trasilol and ?-amine acid. Yet in 30 min after "NovoSeven" administration, hemorrhages seized virtually in all patients irrespective of a surgical intervention. It normalized the hemostasis by it differential action on an impairment depending on an activated or suppressed coagulation. Thus, the conclusion is that the "NovoSeven" (rFVIIa) is an effective hemostatic ensuring the correction of massive intra- and postoperative blood losses in cardiosurgery patients. The drug cuts the need in using the donor-blood components, thus, diminishing the risk of multi organ failure that can develop immediately after surgery.

Achieving hemostasis in dermatology – Part 1: Preoperative, intraoperative, and postoperative management

PubMed Central

Kaur, Ravneet Ruby; Glick, Jaimie B.; Siegel, Daniel

2013-01-01

As dermatological procedures continue to become increasingly complex, improved methods and tools to achieve appropriate hemostasis become necessary. The methods for achieving adequate hemostasis are variable and depend greatly on the type of procedure performed and the unique characteristics of the individual patient. In Part 1 of this review, we discuss the preoperative, intraoperative, and postoperative management of patients undergoing dermatologic surgery. We address oral medications and supplements that affect hemostasis, hemostatic anesthesia, and intraoperative interventions such as suture ligation and heat-generating cautery devices. In Part 2 of this review, we will discuss topical hemostats. The authors conducted an extensive literature review using the following keywords: “hemostasis,” “dermatology,” “dermatological surgery,” “dermatologic sutures,” “electrosurgery,” “hemostatic anesthesia,” and “laser surgery.” Sources for this article were identified by searching the English literature in the Pubmed database for the time period from 1940 to March 2012. A thorough bibliography search was also conducted and key references were examined. PMID:23741660

[Hemostatic and analgesic effect of Gonghuan Zhixue Tablet on mice].

PubMed

Fu, Ling-Mei; You, Zhao-Ling; Lei, Lei; Wen, Le-Xi; Chen, Huan-Ming

2004-03-01

To explore the hemostatic and analgesic effect of Gonghuan Zhixue Tablet (GHZXT) on mice and to produce experimental evidence for exploiting new drug for endometrorrhagia caused by Cu-intrauterine contraceptive device (Cu-IUD). Compared with 6-aminocaproic acid and notoginseng, the effects of GHZXT on clotting and bleeding time of mice with capillary method and severed tail were investigated; and compared with aspirin, the analgesic effects of GHZXT on mice were investigated with hot plate and torsive body method. The clotting time of mice was remarkably shortened with a rising of the dosage of GHZXT and the difference between each therapeutic group and distilled water group was remarkable. As compared with distilled water group, the bleeding time of each dosage group of GHZXT was obviously shortened; and each dosage of GHZXT could prolong the time of pain reaction to hot plate and decrease the degree of torsive body of the mice. Pharmacological experiment has proved that GHZXT has evident hemostatic and analgesic function.

Hemostatic gauze based on chitosan and hydroquinone: preparation, characterization and blood coagulation evaluation.

PubMed

Cassano, Roberta; Di Gioia, Maria Luisa; Mellace, Silvia; Picci, Nevio; Trombino, Sonia

2017-11-07

This work concerns on the preparation and performance evaluation of a new chitosan hydroquinone based gauze for hemostatic use. Chitosan and hydroquinone were firstly connected by etherification and then linked to the pre-carboxylate gauze. The functionalized material and the chitosan-hydroquinone ether were characterized by Fourier Transform Infrared (FT-IR) Spectroscopy and Differential Scanning Calorimetry (DSC). FT-IR results showed that an esterification occurred on carboxylic group of the gauze. The gauze functionalization degree was also evaluated by volumetric analysis. The ether hydroquinone content was obtained by the Folin test. Moreover, the linkage between hydroquinone and chitosan was confirmed by nuclear magnetic resonance (NMR). The hemostatic activity of functionalized gauze was evaluated by dynamic blood clotting assays. The obtained results showed that the prepared material can shorten the blood clotting time and induce the adhesion and activation of platelets. Finally, swelling characteristic of the new gauze was evaluated to confirm its high capacity to absorb the blood.

Influence of Hemostatic Solution on Bond Strength and Physicochemical Properties of Resin Cement.

PubMed

Araújo, Isabela Sousa de; Prado, Célio Jesus do; Raposo, Luís Henrique Araújo; Soares, Carlos José; Zanatta, Rayssa Ferreira; Torres, Carlos Rocha Gomes; Ruggiero, Reinaldo; Silva, Gisele Rodrigues da

2017-01-01

The aim of this study was to evaluate the degree of conversion, color stability, chemical composition, and bond strength of a light-cured resin cement contaminated with three different hemostatic solutions. Specimens were prepared for the control (uncontaminated resin cement) and experimental groups (resin cement contaminated with one of the hemostatic solutions) according to the tests. For degree of conversion, DC (n = 5) and color analyses (n = 10), specimens (3 mm in diameter and 2 mm thick) were evaluated by Fourier transform infrared spectroscopy (FTIR) and CIELAB spectrophotometry (L*, a*, b*), respectively. For elemental chemical analysis (n = 1), specimens (2 mm thick and 6 mm in diameter) were evaluated by x-ray energy-dispersive spectroscopy (EDS). The bond strengths of the groups were assessed by the microshear test (n = 20) in a leucite-reinforced glass ceramic substrate, followed by failure mode analysis by scanning electron microscopy (SEM). The mean values, except for the elemental chemical evaluation and failure mode, were evaluated by ANOVA and Tukey's HSD test. The color stability was influenced by storage time (p<0.001) and interaction between contamination and storage time (p<0.001). Hemostop and Viscostat Clear contamination did not affect the DC, however Viscostat increased the DC. Bond strength of the resin cement to ceramic was negatively affected by the contaminants (p<0.001). Contamination by hemostatic agents affected the bond strength, degree of conversion, and color stability of the light-cured resin cement tested.

Rapid hemostatic and mild polyurethane-urea foam wound dressing for promoting wound healing.

PubMed

Liu, Xiangyu; Niu, Yuqing; Chen, Kevin C; Chen, Shiguo

2017-02-01

A novel rapid hemostatic and mild polyurethane-urea foam (PUUF) wound dressing was prepared by the particle leaching method and vacuum freeze-drying method using 4, 4-Methylenebis(cyclohexyl isocyanate), 4,4-diaminodicyclohexylmethane and poly (ethylene glycol) as raw materials. And X-ray diffraction (XRD), tensile test, differential scanning calorimetry (DSC) and thermogravimetry (TG) were used to its crystallinity, stress and strain behavior, and thermal properties, respectively. Platelet adhesion, fibrinogen adhesion and blood clotting were performed to evaluate its hemostatic effect. And H&E staining and Masson Trichrome staining were used to its wound healing efficacy. The results revealed the pore size of PUUF is 50-130μm, and its porosity is 71.01%. Porous PUUF exhibited good water uptake that was benefit to adsorb abundant wound exudates to build a regional moist environment beneficial for wound healing. The PUUF wound dressing exhibit better blood coagulation effect than commercial polyurethane dressing (CaduMedi). Though both PUUF and CaduMedi facilitated wound healing generating full re-epithelialization within 13days, PUUF was milder and lead to more slight inflammatory response than CaduMedi. In addition, PUUF wound dressing exhibited lower cytotoxicity than CaduMedi against NIH3T3 cells. Overall, porous PUUF represents a novel mild wound dressing with excellent water uptake, hemostatic effect and low toxicity, and it can promote wound healing and enhance re-epithelialization. Copyright © 2016 Elsevier B.V. All rights reserved.

The Impact of 10 Years of War on Combat Casualty Care Research: A Citation Analysis

DTIC Science & Technology

2012-01-01

2004 74 14 Alam HB, Chen Z, Jaskille A, et al. Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin...Among the preclinical studies, the most cited was #14 by Alam et al. (2004), ‘‘Application of a zeolite hemostatic agent achieves 100% survival in a...patients. J Trauma. 2006;60:363Y370. 2006 44 47 Wright JK, Kalns J, Wolf EA, et al. Thermal injury resulting from application of a granular mineral

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

PubMed Central

Pakbaz, Zahra; Wun, Ted

2014-01-01

Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271

Advanced Hemostatic Dressing Development Program: Animal Model Selection Criteria and Results of a Study of Nine Hemostatic Dressings in a Model of Severe Large Venous Hemorrhage and Hepatic Injury in Swine

DTIC Science & Technology

2003-09-01

Pharmaceuticals, Inc. (Westlake, OH), submitted the Hemarrest dressing. This dressing was a thin, sheet-like pad with a mixture of epsilon aminocaproic acid ...chloric acid salt purified bovine corium collagen. It was prepared in a compacted nonwoven web form (7.0 7.0 cm). Ethicon, Inc. (Somerville, NJ...may be related to enhanced platelet procoagulant activity and annexin V binding.46 Another derivative of gallic acid , bis- muth subgallate, appears to

Comparison of New Hemostatic Granules/Powders With Currently Deployed Hemostatic Products in a Lethal Model of Extremity Arterial Hemorrhage in Swine

DTIC Science & Technology

2009-02-01

femoral vein and nerve was avoided. The vessel was then bathed with a few milliliters of 2% lidocaine to relax vasospasm and dilate the artery to its...stop the bleeding resulting in the eventual exsanguination of all tested pigs. Since the army field dress- ing was found to be ineffective in this...efficacy rate was 92% with eight cases of ineffectiveness in morbid patients with possible coagulopathy. The inability to deliver the material to the

The regulation of inflammatory pathways and infectious disease of the cervix by seminal fluid.

PubMed

Adefuye, Anthonio; Katz, Arieh Anthony; Sales, Kurt Jason

2014-01-01

The connection between human papillomavirus (HPV) infection and the consequent sequelae which establishes cervical neoplastic transformation and invasive cervical cancer has redefined many aspects of cervical cancer research. However there is still much that we do not know. In particular, the impact of external factors, like seminal fluid in sexually active women, on pathways that regulate cervical inflammation and tumorigenesis, have yet to be fully understood. HPV infection is regarded as the initiating noninflammatory cause of the disease; however emerging evidence points to resident HPV infections as drivers of inflammatory pathways that play important roles in tumorigenesis as well as in the susceptibility to other infections such as human immunodeficiency virus (HIV) infection. Moreover there is emerging evidence to support a role for seminal fluid, in particular, the inflammatory bioactive lipids, and prostaglandins which are present in vast quantities in seminal fluid in regulating pathways that can exacerbate inflammation of the cervix, speed up tumorigenesis, and enhance susceptibility to HIV infection. This review will highlight some of our current knowledge of the role of seminal fluid as a potent driver of inflammatory and tumorigenic pathways in the cervix and will provide some evidence to propose a role for seminal plasma prostaglandins in HIV infection and AIDS-related cancer.

The Regulation of Inflammatory Pathways and Infectious Disease of the Cervix by Seminal Fluid

PubMed Central

Katz, Arieh Anthony

2014-01-01

The connection between human papillomavirus (HPV) infection and the consequent sequelae which establishes cervical neoplastic transformation and invasive cervical cancer has redefined many aspects of cervical cancer research. However there is still much that we do not know. In particular, the impact of external factors, like seminal fluid in sexually active women, on pathways that regulate cervical inflammation and tumorigenesis, have yet to be fully understood. HPV infection is regarded as the initiating noninflammatory cause of the disease; however emerging evidence points to resident HPV infections as drivers of inflammatory pathways that play important roles in tumorigenesis as well as in the susceptibility to other infections such as human immunodeficiency virus (HIV) infection. Moreover there is emerging evidence to support a role for seminal fluid, in particular, the inflammatory bioactive lipids, and prostaglandins which are present in vast quantities in seminal fluid in regulating pathways that can exacerbate inflammation of the cervix, speed up tumorigenesis, and enhance susceptibility to HIV infection. This review will highlight some of our current knowledge of the role of seminal fluid as a potent driver of inflammatory and tumorigenic pathways in the cervix and will provide some evidence to propose a role for seminal plasma prostaglandins in HIV infection and AIDS-related cancer. PMID:25180120

Microfluidic cardiac cell culture model (μCCCM).

PubMed

Giridharan, Guruprasad A; Nguyen, Mai-Dung; Estrada, Rosendo; Parichehreh, Vahidreza; Hamid, Tariq; Ismahil, Mohamed Ameen; Prabhu, Sumanth D; Sethu, Palaniappan

2010-09-15

Physiological heart development and cardiac function rely on the response of cardiac cells to mechanical stress during hemodynamic loading and unloading. These stresses, especially if sustained, can induce changes in cell structure, contractile function, and gene expression. Current cell culture techniques commonly fail to adequately replicate physical loading observed in the native heart. Therefore, there is a need for physiologically relevant in vitro models that recreate mechanical loading conditions seen in both normal and pathological conditions. To fulfill this need, we have developed a microfluidic cardiac cell culture model (μCCCM) that for the first time allows in vitro hemodynamic stimulation of cardiomyocytes by directly coupling cell structure and function with fluid induced loading. Cells are cultured in a small (1 cm diameter) cell culture chamber on a thin flexible silicone membrane. Integrating the cell culture chamber with a pump, collapsible pulsatile valve and an adjustable resistance element (hemostatic valve) in series allow replication of various loading conditions experienced in the heart. This paper details the design, modeling, fabrication and characterization of fluid flow, pressure and stretch generated at various frequencies to mimic hemodynamic conditions associated with the normal and failing heart. Proof-of-concept studies demonstrate successful culture of an embryonic cardiomyoblast line (H9c2 cells) and establishment of an in vivo like phenotype within this system.

Refined methods to evaluate the in vivo hemostatic function and viability of transfused human platelets in rabbit models.

PubMed

Watanabe, Naohide; Nogawa, Masayuki; Ishiguro, Mariko; Maruyama, Hitomi; Shiba, Masayuki; Satake, Masahiro; Eto, Koji; Handa, Makoto

2017-08-01

To bridge the gap between in vitro function and clinical efficacy of platelet (PLT) transfusion products, reliable in vivo PLT functional assays for hemostasis and survival in animal models are required. However, there are no standardized methods for assessing the in vivo quality of transfused human PLTs. Plasma-depleted human PLT concentrates (PCs; Day 3, Day 5, Day 7, Day 10, and damaged) were transfused into busulfan-induced rabbits with thrombocytopenia with prolonged bleeding times 1 day after treatment with ethyl palmitate (EP) to block their reticuloendothelial systems. The hemostatic effect of PC transfusion was evaluated by the ear fine vein bleeding time. For the in vivo survival assay, splenectomized EP-treated rabbits were transfused with human PCs, and viability of the human PLTs in the rabbits was determined by flow cytometry using human PLT-specific antibodies and Trucount tubes. The hemostatic effect of PCs was slightly reduced with increasing storage periods for early time points, but more dramatically reduced for later time points. PLT survival was similar after 3 and 7 days of storage, but PLTs stored for 10 days showed significantly poorer survival than those stored only 3 days. Our new and improved protocol for in vivo assessment of transfused PLTs is sufficiently sensitive to detect subtle changes in hemostatic function and viability of human PLTs transfused into rabbit models. This protocol could contribute to preclinical in vivo functional assessment and clinical quality assurance of emerging novel PLT products such as cultured cell-derived human PLTs. © 2017 AABB.

Randomized clinical trial comparing cold knife conization of the cervix with and without lateral hemostatic sutures.

PubMed

Bueno, Letícia Rossi; Binda, Marcia; Monego, Heleusa; Scherer, Roberta Luísa; Rolim, Karen Machado; Bottini, Alessandra Leal; Fregnani, José H T G; dos Reis, Ricardo

2015-06-01

Compare blood loss during cold knife conization of the cervix with and without lateral hemostatic sutures in the cervical branches of the uterine arteries. Randomized clinical trial. Hospital de Clínicas de Porto Alegre (HCPA). 102 patients that underwent cold knife conization. Women that underwent cold knife conization of the cervix were randomized to undergo the procedure with or without lateral hemostatic sutures. blood loss measured in grams. operative time and postoperative intervention. Only the participants were blinded to group assignment. From March 2009 to August 2012, patients were randomly assigned to one of the study groups. There were no differences in amount of blood loss between patients that underwent the procedure with and without sutures (p = 0.39). Operative time was shorter in the group without suture (p = 0.020). There were no differences in intervention due to bleeding (p = 0.20). Blood loss was greater among menstruating women than for menopausal women (p = 0.011). There were no differences in amount of blood lost between smoking and nonsmoking patients (p = 0.082). Lateral hemostatic sutures do not affect the amount of intraoperative bleeding or the number of postoperative interventions. Their use is not necessary because they result in longer operative time, have a higher cost due to the use of suture material and pose the risk of ureter lesion in case the sutures are not placed at a lower position in the cervix. ClinicalTrials. gov identifier: NCT02184975. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Hemostatic Effects of Microbubble-Enhanced Low-Intensity Ultrasound in a Liver Avulsion Injury Model

PubMed Central

Feng, Guiying; Liu, Jianhua; Zhao, Xiaochen; Wei, Jinglu; Ou, Wencai; Xiao, Shuyi; Hu, Zhiwen; Wei, Hongqin; Liu, Zheng

2014-01-01

Objectives Microbubble-enhanced therapeutic ultrasound (MEUS) can block the blood flow in the organs. The aim of this study was to evaluate the hemostatic effect of microbubble-enhanced pulsed, low-intensity ultrasound in a New Zealand White rabbit model of avulsion trauma of the liver. The therapeutic ultrasound (TUS) transducer was operated with the frequency of 1.2 MHz and an acoustic pressure of 3.4 MPa. Microbubble-(MB) enhanced ultrasound (MEUS) (n = 6) was delivered to the distal part of the liver where the avulsion was created. Livers were treated by TUS only (n = 4) or MB only (n = 4) which served as controls. Bleeding rates were measured and contrast enhanced ultrasound (CEUS) was performed to assess the hemostatic effect, and liver hemoperfusion before and after treatment. Generally, bleeding rates decreased more than 10-fold after the treatment with MEUS compared with those of the control group (P<0.05). CEUS showed significant declines in perfusion. The peak intensity value and the area under the curve also decreased after insonation compared with those of the control group (P<0.05). Histological examination showed cloudy and swollen hepatocytes, dilated hepatic sinusoids, perisinusoidal spaces with erythrocyte accumulation in small blood vessels, obvious hemorrhage around portal areas and scattered necrosis in liver tissues within the insonation area of MEUS Group. In addition, necrosis was found in liver tissue 48 h after insonation. We conclude that MEUS might provide an effective hemostatic therapy for serious organ trauma such as liver avulsion injury. PMID:24788757

Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.

PubMed

Klipping, Christine; Duijkers, Ingrid; Parke, Susanne; Mellinger, Uwe; Serrani, Marco; Junge, Wolfgang

2011-01-01

A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance. The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel. Healthy women aged 18-50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3 mg, 5 days estradiol valerate 2 mg/dienogest 2 mg, 17 days estradiol valerate 2 mg/dienogest 3 mg, 2 days estradiol valerate 1 mg, 2 days placebo) or ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three. Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/levonorgestrel. The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/levonorgestrel.

Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery.

PubMed

Erstad, B L

2001-09-01

To review the use of systemic hemostatic medications for reducing bleeding and transfusion requirements with cardiac surgery. Articles were obtained through computerized searches involving MEDLINE (from 1966 to September 2000). Additionally, several textbooks containing information on the diagnosis and management of bleeding associated with cardiac surgery were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. Due to the large number of randomized investigations involving systemic hemostatic medications for reducing bleeding associated with cardiac surgery, the article selection process focused on recent randomized controlled trials, metaanalyses and pharmacoeconomic evaluations. The primary outcomes extracted from the literature were blood loss and associated transfusion requirements, although other outcome measures such as mortality were extracted when available. Although the majority of investigations for reducing cardiac bleeding and transfusion requirements have involved aprotinin, evidence from recent meta-analyses and randomized trials indicates that the synthetic antifibrinolytic agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy. Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much less costly. More comparative information of hemostatic agents is needed retative to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There is insufficient evidence to recommend the use of desmopressin for reducing bleeding and transfusion requirements in cardiac surgery, although certain subsets of patients may benefit from its use. Of the medications that have been used to reduce bleeding and transfusion requirements with cardiac surgery, the antifibrinolytic agents have the best evidence supporting their use. Aminocaproic acid is the least costly therapy based on medication costs and transfusion requirements.

Conservative management of post-partum hemorrhage secondary to placenta previa-accreta with hypogastric artery ligation and endo-uterine hemostatic suture.

PubMed

Rauf, Melekoglu; Ebru, Celik; Sevil, Eraslan; Selim, Buyukkurt

2017-02-01

The aim of this study was to investigate maternal and neonatal outcomes of conservative management of post-partum hemorrhage due to placenta previa-accreta using hypogastric artery ligation and endo-uterine hemostatic suture to lower uterine segment. The records of 38 patients who were managed conservatively with hypogastric artery ligation and endo-uterine hemostatic suture to control post-partum hemorrhage secondary to placenta previa-accreta between April 2014 and January 2016, were reviewed retrospectively. Placenta previa-accreta was diagnosed according to gray-scale, color and 3-D power Doppler ultrasonography in addition to the intraoperative findings based on fragmentary or difficult separation of the placenta. In the case of conservative treatment protocol failure, cesarean hysterectomy was performed. Of these patients, 55.2% were between 25 and 35 years old; 97.5% were multiparous; 71.2% had two or more previous cesarean section and 68.5% had preterm delivery. Women with placenta accreta had a median estimated blood loss of 450 mL; 57.8% of patients had blood transfusion (mean intraoperative transfusion, 2 units packed red blood cells; range, 0-9 units). Median duration of operation was 112.5 min (range, 45-305 min) and 32 patients (84.3%) with placenta accreta did not undergo cesarean hysterectomy. Conservative treatment of post-partum hemorrhage secondary to placenta previa-accreta with hypogastric artery ligation and endo-uterine hemostatic sutures to the lower segment of the uterus is associated with lower hysterectomy rate compared with the other conservative methods reported in the literature. © 2016 Japan Society of Obstetrics and Gynecology.

Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis.

PubMed

Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar

2017-11-01

OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.

Hydraulic fracturing fluid migration in the subsurface: A review and expanded modeling results

NASA Astrophysics Data System (ADS)

Birdsell, Daniel T.; Rajaram, Harihar; Dempsey, David; Viswanathan, Hari S.

2015-09-01

Understanding the transport of hydraulic fracturing (HF) fluid that is injected into the deep subsurface for shale gas extraction is important to ensure that shallow drinking water aquifers are not contaminated. Topographically driven flow, overpressured shale reservoirs, permeable pathways such as faults or leaky wellbores, the increased formation pressure due to HF fluid injection, and the density contrast of the HF fluid to the surrounding brine can encourage upward HF fluid migration. In contrast, the very low shale permeability and capillary imbibition of water into partially saturated shale may sequester much of the HF fluid, and well production will remove HF fluid from the subsurface. We review the literature on important aspects of HF fluid migration. Single-phase flow and transport simulations are performed to quantify how much HF fluid is removed via the wellbore with flowback and produced water, how much reaches overlying aquifers, and how much is permanently sequestered by capillary imbibition, which is treated as a sink term based on a semianalytical, one-dimensional solution for two-phase flow. These simulations include all of the important aspects of HF fluid migration identified in the literature review and are performed in five stages to faithfully represent the typical operation of a hydraulically fractured well. No fracturing fluid reaches the aquifer without a permeable pathway. In the presence of a permeable pathway, 10 times more fracturing fluid reaches the aquifer if well production and capillary imbibition are not included in the model.

Hemostatic action of OC-108, a novel agent for hemorrhoids, is associated with regional blood flow arrest induced by acute inflammation.

PubMed

Ono, Takashi; Nakagawa, Haruto; Fukunari, Atsushi; Hashimoto, Toshio; Komatsu, Hirotsugu

2006-11-01

Clinically, hemorrhoidal bleeding and prolapse disappeared immediately after injection of the sclerosing agent OC-108 into submucosa of hemorrhoids. The aim of this study was to elucidate the mechanism of action responsible for the immediate hemostatic effect of OC-108 using anesthetized rats. Subcutaneous injection of OC-108 in rats decreased blood flow at the injection site within 5 min. Aluminum potassium sulfate, one of the main ingredients of OC-108, reduced the skin blood flow. However, tannic acid, another main ingredient, did not. By perfusion of OC-108 on the mesenteric surface, microcirculatory blood flow was arrested without remarkable change in blood vessel diameter, accompanied by increased vascular permeability and venous hematocrit. These results indicate that OC-108 induces regional blood flow arrest with rapid onset, this effect being attributed to the action of aluminum potassium sulfate, and that hemoconcentration due to increased vascular permeability (plasma extravasation), an acute inflammatory reaction, is involved in the mechanisms of the immediate hemostatic action of OC-108.

Peritoneal fluid transport: mechanisms, pathways, methods of assessment.

PubMed

Waniewski, Jacek

2013-11-01

Fluid removal during peritoneal dialysis is controlled by many mutually dependent factors and therefore its analysis is more complex than that of the removal of small solutes used as markers of dialysis adequacy. Many new tests have been proposed to assess quantitatively different components of fluid transport (transcapillary ultrafiltration, peritoneal absorption, free water, etc.) and to estimate the factors that influence the rate of fluid transport (osmotic conductance). These tests provide detailed information about indices and parameters that describe fluid transport, especially those concerning the problem of the permanent loss of ultrafiltration capacity (ultrafiltration failure). Different theories and respective mathematical models of mechanisms and pathways of fluid transport are presently discussed and applied, and some fluid transport issues are still debated. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro

PubMed Central

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-01-01

Aim: To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Methods: Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Results: Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca2+ concentration, while Na+ and K+ concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca2+ and Na+ concentrations. Si4+ (0.2434 g/L) and Al3+ (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca2+ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Conclusion: Zeolite releases Ca2+ into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time. PMID:23334236

Serum bilirubin levels are inversely associated with PAI-1 and fibrinogen in Korean subjects.

PubMed

Cho, Hyun Sun; Lee, Sung Won; Kim, Eun Sook; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun

2016-01-01

Oxidative stress may contribute to atherosclerosis and increased activation of the coagulation pathway. Bilirubin may reduce activation of the hemostatic system to inhibit oxidative stress, which would explain its cardioprotective properties shown in many epidemiological studies. This study investigated the association of serum bilirubin with fibrinogen and plasminogen activator inhibitor-1 (PAI-1), respectively. A cross-sectional analysis was performed on 968 subjects (mean age, 56.0 ± 11.2 years; 61.1% men) undergoing a general health checkup. Serum biochemistry was analyzed including bilirubin subtypes, insulin resistance (using homeostasis model of assessment [HOMA]), C-reactive protein (CRP), fibrinogen, and PAI-1. Compared with subjects with a total bilirubin (TB) concentration of <10.0 μmol/L, those with a TB concentration of >17.1 μmol/L had a smaller waist circumference, a lower triglyceride level, a lower prevalence of metabolic syndrome, and decreased HOMA-IR and CRP levels. Correlation analysis revealed linear relationships of fibrinogen with TB and direct bilirubin (DB), whereas PAI-1 was correlated with DB. After adjustment for confounding factors, bilirubin levels were inversely associated with fibrinogen and PAI-1 levels, respectively. Multivariate regression models showed a negative linear relationship between all types of bilirubin and fibrinogen, whereas there was a significant linear relationship between PAI-1 and DB. High bilirubin concentrations were independently associated with low levels of fibrinogen and PAI-1, respectively. The association between TB and PAI-1 was confined to the highest TB concentration category whereas DB showed a linear association with PAI-1. Bilirubin may protect against the development of atherothrombosis by reducing the hemostatic response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

PubMed

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-03-01

To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca(2+) concentration, while Na(+) and K(+) concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca(2+) and Na(+) concentrations. Si(4+) (0.2434 g/L) and Al(3+) (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca(2+) concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca(2+) into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

Long- and Short-Term Exposure To Air Pollution and Inflammatory/Hemostatic Markers in Midlife Women

PubMed Central

Green, Rochelle; Broadwin, Rachel; Malig, Brian; Basu, Rupa; Gold, Ellen B.; Qi, Lihong; Sternfeld, Barbara; Bromberger, Joyce T.; Greendale, Gail A.; Kravitz, Howard M.; Tomey, Kristin; Matthews, Karen; Derby, Carol; Jackson, Elizabeth A.; Green, Robin; Ostro, Bart

2016-01-01

Background Studies have reported associations between long-term air pollution exposures and cardiovascular mortality. The biological mechanisms connecting them remain uncertain. Methods We examined associations of fine particles (PM2.5) and ozone with serum markers of cardiovascular disease risk in a cohort of midlife women. We obtained information from women enrolled at six sites in the multi-ethnic, longitudinal Study of Women's Health Across the Nation, including repeated measurements of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, tissue-type plasminogen activator antigen (tPA-ag), plasminogen activator inhibitor Type 1 (PAI-1), and Factor VIIc (Factor VII coagulant activity). We obtained residence-proximate PM2.5 and ozone monitoring data for a maximum five annual visits, calculating prior year, six-month, one-month, and one-day exposures and their relations to serum markers using longitudinal mixed models. Results For the 2,086 women studied from 1999 through 2004, PM2.5 exposures were associated with all blood markers except Factor VIIc after adjusting for age, race/ethnicity, education, site, body mass index, smoking, and recent alcohol use. Adjusted associations were of the strongest for prior year exposures for hs-CRP (21% increase per 10 μg/m3 PM2.5, 95% CI: 6.6, 37), tPA-ag (8.6%, 95% CI: 1.8, 16), and PAI-1 (35%, 95% CI: 19, 53). An association was also observed between year prior ozone exposure and Factor VIIc (5.7% increase per 10 ppb ozone, 95% CI: 2.9, 8.5). Conclusions Our findings suggest that prior year exposures to PM2.5 and ozone are associated with adverse effects on inflammatory and hemostatic pathways for cardiovascular outcomes in midlife women. PMID:26600256

[Modern biomaterials as hemostatic dressings in kidney nephron sparing surgery (NSS)--murine model. A preliminary report].

PubMed

Nowacki, Maciej; Jundziłł, Arkadiusz; Bieniek, Miłosz; Kowalczyk, Tomasz; Kloskowski, Tomasz; Drewa, Tomasz

2012-01-01

Kidney cancer is now days, one of the main problems in oncological urology. More frequent cases detection of this type of cancer and the implementation of modern methods of treatment, involves the public and good diagnostic radiological imaging methods. Approximately 40% of renal tumors are detected clinically as a changes in T1N0M0 stage. This means that in these patients, surgery can be performed using the method of nephron sparing surgery (NSS), far from consisting the implementation of radical nephrectomy. Unfortunately, despite the saving nature of this type of treatment, NSS methods are associated with local recurrence of tumor formation. Another problem is intra operative bleeding, that's why in order to stop this negative process surgeons currently use hemostatic dressings. Potentially and clinically significant solution could be a combination of this two main problematics points of concern, through the use of modern biomaterials coated on oncostatic substances as a haemostatic dressings, to the prevention of tumor recurrence. The aim of this work, was to present preliminary report of the use of advanced biomaterials, as haemostatic dressings in an experimental technique of nephron sparing surgery on an murine model. In the experiment we use two types of biomaterials and the standard haemostatic dressing used in the nephron sparing surgery (NSS) as a control. We use a polycaprolactone biomaterial obtained by electrospinning. As a second type of biomaterial, we use a homogeneous material with a structure similar to wool, also obtained from medical polycaprolactone by electrospinning. As an murine (in vivo) model in the study, we use 10 C57BL/J mice (with the local ethical committee permission). 8 mice were used in the present study, 2 mice were constituted as a separate control for obtaining the bleeding data. Kidney melanoma cells were implanted under the C57B1/J B16 mouse kidney fibrous capsule, one week before NSS. After 3 weeks the animals were sacrificed for comparison of hemostatic dressings function. Used biomaterials fulfilled their role as a hameostatic dresings. The material (Type I) was convenient and good for suturing. Haemostatic action times were as follows: (Type I) - 30 seconds. (Type III) - 50 seconds. In the control group were also observed, a proper hemostatic function after 30 seconds. In sectional observation was also found in 3 kidneys section preparation samples, a local tumor recurrence and metastasis to the other tissues of the abdomen. The tested biomaterials fulfill their hemostatic effect on kidney after NSS, without any significant difference acording to a standard hemostatic dressing used clinically. This data may be a potential factor for use in further studies to determine their continued relevance in the prevention of local tumor recurrence after nephron sparing surgery.

Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

PubMed

Puy, Cristina; Tucker, Erik I; Ivanov, Ivan S; Gailani, David; Smith, Stephanie A; Morrissey, James H; Gruber, András; McCarty, Owen J T

2016-01-01

Factor (F) XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa) promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα), in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP) derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin. Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma. Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

[Medication regularity and potential targets of Professor XU Jing-fan's prescription for treating ulcerative colitis].

PubMed

Ning, Li-Qin; Ye, Bai; Shen, Hong; Lu, Wei-Min; Xu, Dan-Hua; Yan, Jing; Tan, Chang; Tang, De-Cai

2018-03-01

Ulcerative colitis (UC) is a chronic nonspecific inflammation mainly involving rectum and colon mucosa, which seriously affects the health and quality of life of patients, and is listed as one of modern refractory diseases by WHO. Professor XU Jing-fan, a great master of traditional Chinese medicine, has accumulated rich experiences in the treatment of UC. The study collected Professor XU's 77 prescriptions of treating UC, analyzed the frequency of traditional Chinese medicines and there categories, and investigated the medication regularity by the system clustering method. The findings showed that the most frequently used drugs were clearing-heat herbs, which were followed by hemostatic herbs, excreting-dampness herbs, improving-digestion herbs and tonifying-Qi herbs. At the same time, the commonly combined drugs were excavated. Finally, in order to analyze potential molecular targets of the frequently used herbs, GO enrichment analysis and KEGG signal pathway enrichment analysis were performed with bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM). The results indicated that Chinese herbal compounds may treat UC by activating PPAR-γ pathway and regulating intestinal inflammation. The exact mechanisms shall be verified through subsequent molecular biological experiments. Copyright© by the Chinese Pharmaceutical Association.

Proteolytic inactivation of tissue factor pathway inhibitor by bacterial omptins

PubMed Central

Yun, Thomas H.; Cott, Jessica E.; Tapping, Richard I.; Slauch, James M.

2009-01-01

The immune response to infection includes activation of the blood clotting system, leading to extravascular fibrin deposition to limit the spread of invasive microorganisms. Some bacteria have evolved mechanisms to counteract this host response. Pla, a member of the omptin family of Gram-negative bacterial proteases, promotes the invasiveness of the plague bacterium, Yersinia pestis, by activating plasminogen to plasmin to digest fibrin. We now show that the endogenous anticoagulant tissue factor pathway inhibitor (TFPI) is also highly sensitive to proteolysis by Pla and its orthologs OmpT in Escherichia coli and PgtE in Salmonella enterica serovar Typhimurium. Using gene deletions, we demonstrate that bacterial inactivation of TFPI requires omptin expression. TFPI inactivation is mediated by proteolysis since Western blot analysis showed that TFPI cleavage correlated with loss of anticoagulant function in clotting assays. Rates of TFPI inactivation were much higher than rates of plasminogen activation, indicating that TFPI is a better substrate for omptins. We hypothesize that TFPI has evolved sensitivity to proteolytic inactivation by bacterial omptins to potentiate procoagulant responses to bacterial infection. This may contribute to the hemostatic imbalance in disseminated intravascular coagulation and other coagulopathies accompanying severe sepsis. PMID:18988866

Visualization of liposomes carrying fibrinogen gamma-chain dodecapeptide accumulated to sites of vascular injury using computed tomography.

PubMed

Okamura, Yosuke; Eto, Kaoruko; Maruyama, Hitomi; Handa, Makoto; Ikeda, Yasuo; Takeoka, Shinji

2010-04-01

We have constructed liposomes with hemostatic activity as a platelet substitute using moderately thrombocytopenic rats. The liposomes were conjugated with the dodecapeptide (HHLGGAKQAGDV: H12), which is a fibrinogen gamma-chain C-terminal sequence (gamma 400-411). To visualize liposome accumulation at the site of vascular injury by in vivo computed tomography, a water-soluble contrast dye, N,N'-bis[2-hydroxy-1-(hydroxylmethyl)ethyl]-5-[(2S)-2-hydroxylpropanoylamino]-2,4,6-triiodoisophthalamide (iopamidol), was encapsulated into the H12-conjugated liposomes. We achieved direct visualization of specific accumulation of the H12-(iopamidol)liposomes at the jugular vein injured by ferric chloride and succeeded in semiquantitative analyses of the accumulated amount of H12-liposomes in the injured site. We therefore propose that H12-liposomes that are specifically recruited to, and exert their hemostatic activity at the site of vascular injury, have a significant potential as a carrier and/or as an ideal platelet substitute. Furthermore, the H12-(iopamidol)liposomes would also be clinically useful as diagnostic agents for pathological thrombus detection and as contrast dyes for hepatosplenography. The authors have constructed liposomes with hemostatic activity as a platelet substitute using moderately thrombocytopenic rats. They propose that H12-liposomes that are specifically recruited to, and exert their hemostatic activity at the site of vascular injury, have a significant potential as a carrier and/or as an ideal platelet substitute. Furthermore, the H12-(iopamidol) liposomes would also be clinically useful as diagnostic agents for thrombus detection and as contrast dyes for hepatosplenography. Copyright 2010 Elsevier Inc. All rights reserved.

Neutrophil interaction with the hemostatic system contributes to liver injury in rats cotreated with lipopolysaccharide and ranitidine.

PubMed

Deng, Xiaomin; Luyendyk, James P; Zou, Wei; Lu, Jingtao; Malle, Ernst; Ganey, Patricia E; Roth, Robert A

2007-08-01

Cotreatment of rats with nontoxic doses of ranitidine (RAN) and lipopolysaccharide (LPS) causes liver injury, and this drug-inflammation interaction might be a model for idiosyncratic adverse drug responses in humans. Both polymorphonuclear neutrophils (PMNs) and the hemostatic system have been shown to be important in the injury. We tested the hypothesis that PMNs cause liver injury by interacting with the hemostatic system and producing subsequent hypoxia. In rats cotreated with LPS/RAN, PMN depletion by anti-PMN serum reduced fibrin deposition and hypoxia in the liver. PMN depletion also reduced the plasma concentration of active plasminogen activator inhibitor-1 (PAI-1), a major down-regulator of the fibrinolytic system. This suggests that PMNs promote fibrin deposition by increasing PAI-1 concentration. PMNs were activated in the livers of LPS/RAN-cotreated rats as evidenced by increased staining for hypochlorous acid-modified proteins generated by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes. Antiserum against the PMN adhesion molecule CD18 protected against LPS/RAN-induced liver injury. Because CD18 is important for PMN transmigration and activation, these results suggest that PMN activation is required for the liver injury. Furthermore, anti-CD18 serum reduced biomarkers of hemostasis and hypoxia, suggesting the necessity for PMN activation in the interaction between PMNs and the hemostatic system/hypoxia. Liver injury, liver fibrin, and plasma PAI-1 concentration were also reduced by eglin C, an inhibitor of proteases released by activated PMNs. In summary, PMNs are activated in LPS/RAN-cotreated rats and participate in the liver injury in part by contributing to hemostasis and hypoxia.

Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria.

PubMed

Collier, A; Rumley, A; Rumley, A G; Paterson, J R; Leach, J P; Lowe, G D; Small, M

1992-08-01

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrin, γ’-fibrinogen, and trans-clot pressure gradient control hemostatic clot growth during human blood flow over a collagen/tissue factor wound

PubMed Central

Muthard, Ryan W.; Welsh, John D.; Brass, Lawrence F.; Diamond, Scott L.

2015-01-01

SUMMARY Objective Biological and physical factors interact to modulate blood response in a wounded vessel, resulting in a hemostatic clot or an occlusive thrombus. Flow and pressure differential (ΔP) across the wound from the lumen to the extravascular compartment may impact hemostasis and the observed core/shell architecture. We examined physical and biological factors responsible for regulating thrombin mediated clot growth. Approach and Results Using factor XIIa-inhibited human whole blood perfused in a microfluidic device over collagen/tissue factor at controlled wall shear rate and ΔP, we found thrombin to be highly localized in the P-selectin+ core of hemostatic clots. Increasing ΔP from 9 to 29 mm-Hg (wall shear rate = 400 s−1) reduced P-selectin+ core size and total clot size due to enhanced extravasation of thrombin. Blockade of fibrin polymerization with 5 mM GPRP dysregulated hemostasis by enhancing both P-selectin+ core size and clot size at 400 s−1 (20 mm-Hg). For whole blood flow (no GPRP), the thickness of the P-selectin-negative shell was reduced under arterial conditions (2000 s−1, 20 mm-Hg). Consistent with the antithrombin-1 activity of fibrin implicated with GPRP, anti-γ’-fibrinogen antibody enhanced core-localized thrombin, core size, and overall clot size, especially at venous (100 s−1) but not arterial wall shear rates (2000 s−1). Pathological shear (15,000 s−1) and GPRP synergized to exacerbate clot growth. Conclusions Hemostatic clotting was dependent on core-localized thrombin that (1) triggered platelet P-selectin display and (2) was highly regulated by fibrin and the trans-clot ΔP. Also, γ’-fibrinogen had a role in venous but not arterial conditions. PMID:25614284

Antimicrobial activity of chemomechanical gingival retraction products.

PubMed

Hsu, Belinda; Lee, Stephanie; Schwass, Donald; Tompkins, Geoffrey

2017-07-01

Application of astringent hemostatic agents is the most widely used technique for gingival retraction, and a variety of products are offered commercially. However, these products may have additional unintended yet clinically beneficial properties. The authors assessed the antimicrobial activities of marketed retraction products against plaque-associated bacteria in both planktonic and biofilm assays, in vitro. The authors assessed hemostatic solutions, gels, pellets, retraction cords, pastes, and their listed active agents against a collection of microorganisms by means of conventional agar diffusion and minimum bacteriostatic and bactericidal concentration determinations. The authors then tested the most active products against monospecies biofilms grown on hydroxyapatite disks. All of the tested retraction products exhibited some antimicrobial activity. The results of the most active products were comparable with those of a marketed mouthwash. The listed retraction-active agents displayed relatively little activity when tested in pure form. At 10% dilution, some products evidenced inhibitory activity against most tested bacteria within 3 minutes of exposure, whereas others displayed variable effects after 10 minutes. The most active agents reduced, but did not completely prevent, the metabolic activity of a monospecies biofilm. Commercial gingival retraction products exhibit antimicrobial effects to various degrees in vitro. Some products display rapid bactericidal activity. The antimicrobial activity is not owing to the retraction-active agents. Biofilm bacteria are less sensitive to the antimicrobial effects of the agents. The rapidity of killing by some hemostatic agents suggests an antimicrobial effect that may be efficacious during clinical placement. The results of this in vitro study suggest that clinicians should be aware of the potential antimicrobial effects of some hemostatic agents, but more research is needed to confirm these observations in clinical use. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Local hemostatic matrix for endoscope-assisted removal of intracerebral hemorrhage is safe and effective.

PubMed

Luh, Hui-Tzung; Huang, Abel Po-Hao; Yang, Shih-Hung; Chen, Chien-Ming; Cho, Der-Yang; Chen, Chun-Chung; Kuo, Lu-Ting; Li, Chieh-Hsun; Wang, Kuo-Chuan; Tseng, Wei-Lung; Hsing, Ming-Tai; Yang, Bing-Shiang; Lai, Dar-Ming; Tsai, Jui-Chang

2018-01-01

Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings. Copyright © 2017. Published by Elsevier B.V.

Low hemorrhage-related mortality in trauma patients in a Level I trauma center employing transfusion packages and early thromboelastography-directed hemostatic resuscitation with plasma and platelets.

PubMed

Johansson, Pär I; Sørensen, Anne Marie; Larsen, Claus F; Windeløv, Nis A; Stensballe, Jakob; Perner, Anders; Rasmussen, Lars S; Ostrowski, Sisse R

2013-12-01

Hemorrhage accounts for most preventable trauma deaths, but still the optimal strategy for hemostatic resuscitation remains debated. This was a prospective study of adult trauma patients admitted to a Level I trauma center. Demography, Injury Severity Score (ISS), transfusion therapy, and mortality were registered. Hemostatic resuscitation was based on a massive transfusion protocol encompassing transfusion packages and thromboelastography (TEG)-guided therapy. A total of 182 patients were included (75% males, median age 43 years, ISS of 17, 92% with blunt trauma). Overall 28-day mortality was 12% with causes of death being exsanguinations (14%), traumatic brain injury (72%, two-thirds expiring within 24 hr), and other (14%). One-fourth, 16 and 15% of the patients, received red blood cells (RBCs), plasma, or platelets (PLTs) within 2 hours from admission and 68, 71, and 75%, respectively, of patients transfused within 24 hours received the respective blood products within the first 2 hours. In patients transfused within 24 hours, the median number of blood products at 2 hours was 5 units of RBCs, 5 units of plasma, and 2 units of PLT concentrates. Nonsurvivors had lower clot strength by kaolin-activated TEG and TEG functional fibrinogen and lower kaolin-tissue factor-activated TEG α-angle and lysis after 30 minutes compared to survivors. None of the TEG variables were independent predictors of massive transfusion or mortality. Three-fourths of the patients transfused with plasma or PLTs within 24 hours received these in the first 2 hours. Hemorrhage caused 14% of the deaths. We introduced transfusion packages and early TEG-directed hemostatic resuscitation at our hospital 10 years ago and this may have contributed to reducing hemorrhagic trauma deaths. © 2013 American Association of Blood Banks.

Stability of hemostatic proteins in canine fresh-frozen plasma thawed with a modified commercial microwave warmer or warm water bath.

PubMed

Pashmakova, Medora B; Barr, James W; Bishop, Micah A

2015-05-01

To compare stability of hemostatic proteins in canine fresh-frozen plasma (FFP) thawed with a modified commercial microwave warmer (MCM) or warm water bath (37°C; WWB) or at room temperature (22°C). Fresh-frozen plasma obtained from 8 canine donors of a commercial blood bank. A commercial microwave warmer was modified with a thermocouple to measure surface temperature of bags containing plasma. The MCM and a WWB were each used to concurrently thaw a 60-mL bag of plasma obtained from the same donor. Two 3-mL control aliquots of FFP from each donor were thawed to room temperature without use of a heating device. Concentrations of hemostatic proteins, albumin, and D-dimers; prothrombin time (PT); and activated partial thromboplastin time (aPTT) were determined for all samples. Significant decreases in concentrations of factors II, IX, X, XI, fibrinogen, von Willebrand factor, antithrombin, protein C, and albumin and significant increases in PT and aPTT were detected for plasma thawed with the MCM, compared with results for samples thawed with the WWB. Concentrations of factors VII, VIII, and XII were not significantly different between plasma thawed with the MCM and WWB. Concentrations of D-dimers were above the reference range for all thawed samples regardless of thawing method. No significant differences in factor concentrations were detected between control and WWB-thawed samples. Significant differences in hemostatic protein concentrations and coagulation times were detected for plasma thawed with an MCM but not between control and WWB-thawed samples. Clinical importance of these changes should be investigated.

Analysis of Variability in Intraoperative Fluid Administration for Colorectal Surgery: An Argument for Goal-Directed Fluid Therapy.

PubMed

Quinn, Timothy D; Brovman, Ethan Y; Urman, Richard D

2017-09-01

Fluid therapy in the perioperative period varies greatly between anesthesia providers and may have a negative impact on surgical outcomes. We conducted a retrospective analysis of 705 elective colorectal cases consisting of colectomies, ileocolic resections, and low anterior resections at an academic institution from January 1, 2010 to May 29, 2015, collected by our electronic medical record before implementation of Enhanced Recovery After Surgery (ERAS ® ) pathways. The mean for total crystalloid administration was 2578 mL with a standard deviation (SD) that was approximately 50% of the mean value. A combination of both normal saline and lactated Ringer's solution was used in almost all cases without a clear rationale for fluid choice. Fluid administered to patients was disproportional to measured intraoperative fluid losses (estimated blood loss and urine output) by a factor of 10. The average rate of fluid given was 1050 mL/h with an SD of nearly the same amount (951 mL). There was a variability of over 67% in total crystalloid administered based on both ideal body weight and total body weight. We found that a wide variability in the amount and type of fluid therapy administered existed at our institution before implementation of a colorectal ERAS pathway or routine use of goal-directed fluid therapy (GDFT). ERAS pathways with GDFT protocols could lead to more rational and consistent fluid therapy leading to improved outcomes.

The saliva proteome of the blood-feeding insect Triatoma infestans is rich in platelet-aggregation inhibitors

NASA Astrophysics Data System (ADS)

Charneau, Sébastien; Junqueira, Magno; Costa, Camila M.; Pires, Daniele L.; Fernandes, Ellen S.; Bussacos, Ana C.; Sousa, Marcelo V.; Ricart, Carlos André O.; Shevchenko, Andrej; Teixeira, Antonio R. L.

2007-12-01

The saliva of the bloodsucking bug Triatoma infestans vector of Chagas disease contains an anti-hemostatic molecular cocktail that prevents coagulation, vasoconstriction and platelet aggregation in a vertebrate prey. In order to characterize T. infestans saliva proteome, we separated the secreted saliva by two-dimensional gel electrophoresis (2-DE). More than 200 salivary proteins were detected on the 2-DE map, mainly in the alkaline region. By nanoLC-MS/MS analysis using a LTQ-Orbitrap equipment followed by a combination of conventional and sequence-similarity searches, we identified 58 main protein spots. Most of such proteins possess potential blood-feeding associated functions, particularly anti-platelet aggregation proteins belonging to lipocalin and apyrase families. The saliva protein composition indicates a highly specific molecular mechanism of early response to platelet aggregation. This first proteome analysis of the T. infestans secreted saliva provides a basis for a better understanding of this fluid protein composition highly directed to counterpart hemostasis of the prey, thus promoting the bug's blood-feeding.

A Fluid-driven Earthquake Cycle, Omori's Law, and Fluid-driven Aftershocks

NASA Astrophysics Data System (ADS)

Miller, S. A.

2015-12-01

Few models exist that predict the Omori's Law of aftershock rate decay, with rate-state friction the only physically-based model. ETAS is a probabilistic model of cascading failures, and is sometimes used to infer rate-state frictional properties. However, the (perhaps dominant) role of fluids in the earthquake process is being increasingly realised, so a fluid-based physical model for Omori's Law should be available. In this talk, I present an hypothesis for a fluid-driven earthquake cycle where dehydration and decarbonization at depth provides continuous sources of buoyant high pressure fluids that must eventually make their way back to the surface. The natural pathway for fluid escape is along plate boundaries, where in the ductile regime high pressure fluids likely play an integral role in episodic tremor and slow slip earthquakes. At shallower levels, high pressure fluids pool at the base of seismogenic zones, with the reservoir expanding in scale through the earthquake cycle. Late in the cycle, these fluids can invade and degrade the strength of the brittle crust and contribute to earthquake nucleation. The mainshock opens permeable networks that provide escape pathways for high pressure fluids and generate aftershocks along these flow paths, while creating new pathways by the aftershocks themselves. Thermally activated precipitation then seals up these pathways, returning the system to a low-permeability environment and effective seal during the subsequent tectonic stress buildup. I find that the multiplicative effect of an exponential dependence of permeability on the effective normal stress coupled with an Arrhenius-type, thermally activated exponential reduction in permeability results in Omori's Law. I simulate this scenario using a very simple model that combines non-linear diffusion and a step-wise increase in permeability when a Mohr Coulomb failure condition is met, and allow permeability to decrease as an exponential function in time. I show very strong spatial correlations of the simulated evolved permeability and fluid pressure field with aftershock hypocenters from this 1992 Landers and 1994 Northridge aftershock sequences, and reproduce the observed aftershock decay rates. Controls on the decay rates (p-value) will also be discussed.

Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways

PubMed Central

Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, DL; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

2015-01-01

Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm2) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified. PMID:25435370

Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways.

PubMed

Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, D L; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

2015-08-27

Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm(2)) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified.

Splenic injury during percutaneous nephrolithotomy.

PubMed

Thomas, Anil A; Pierce, Gregory; Walsh, R Matthew; Sands, Mark; Noble, Mark

2009-01-01

Injury to the spleen is a recognized complication during percutaneous renal access due to the close anatomical relationship of the spleen and the left kidney. However, transsplenic renal access is a rare complication of percutaneous nephrolithotomy and can also result in considerable morbidity, often requiring emergent splenectomy. We present our experience with splenic injury during percutaneous nephrolithotomy managed conservatively with the use of a collagen-thrombin hemostatic sealant (D-Stat; Vascular Solutions, Inc., Minneapolis, MN) after delayed removal of the nephrostomy tubes. The patient had an uneventful recovery and was discharged home on postoperative day 6. In select hemodynamically stable patients, nonoperative management with the adjunctive use of hemostatic sealants may be considered.

Effects of sulfur-based hemostatic agents and gingival retraction cords handled with latex gloves on the polymerization of polyvinyl siloxane impression materials

PubMed Central

MACHADO, Carlos Eduardo Palhares; GUEDES, Carlos Gramani

2011-01-01

Objectives This study investigated the possible interactions between three addition silicone materials (Express®, Aquasil Ultra® and Adsil®), three hemostatic agents (ferric sulfate, StatGel FS®; aluminum sulfate, GelCord®; and aluminum chloride, Hemostop®) and gingival retraction cords previously handled with latex gloves to determine whether direct contact with medicaments or indirect contamination by latex in conditions similar to those found in clinical practice inhibit or affect the setting of the impression materials. Material and Methods A portable device for the simultaneous test of several specimens was specifically developed for this study. Polymerization inhibition was analyzed by examination of the impressions and the molded surface. Ten trials were performed for each addition silicone material used in the study, at a total of 240 study samples. Results All the samples tested (N=240) were nonreactive regardless of the type of combination used. Conclusions Aluminum sulfate, ferric sulfate and aluminum chloride hemostatic solutions did not show any inhibitory potential on the addition silicone samples under study, and there were no changes in polymerization as a result of contact between addition silicone and retraction cords handled with latex gloves. PMID:22230998

Oral Surgical Procedures Performed Safely in Patients With Head and Neck Arteriovenous Malformations: A Retrospective Case Series of 12 Patients.

PubMed

Karim, Abdul Basit; Lindsey, Sean; Bovino, Brian; Berenstein, Alejandro

2016-02-01

This case series describes patients with head and neck arteriovenous malformations who underwent oral and maxillofacial surgical procedures combined with interventional radiology techniques to minimize blood loss. Twelve patients underwent femoral cerebral angiography to visualize the extent of vascular malformation. Before the surgical procedures, surgical sites were devascularized by direct injection of hemostatic or embolic agents. Direct puncture sclerotherapy at the base of surgical sites was performed using Surgiflo or n-butylcyanoacrylate glue. Surgical procedures were carried out in routine fashion. A hemostatic packing of FloSeal, Gelfoam, and Avitene was adapted to the surgical sites. Direct puncture sclerotherapy with Surgiflo or n-butylcyanoacrylate glue resulted in minimal blood loss intraoperatively. Local application of the FloSeal, Gelfoam, and Avitene packing sustained hemostasis and produced excellent healing postoperatively. Patients with arteriovenous malformations can safely undergo routine oral and maxillofacial surgical procedures with minimal blood loss when appropriate endovascular techniques and local hemostatic measures are used by the interventional radiologist and oral and maxillofacial surgeon. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of sulfur-based hemostatic agents and gingival retraction cords handled with latex gloves on the polymerization of polyvinyl siloxane impression materials.

PubMed

Machado, Carlos Eduardo Palhares; Guedes, Carlos Gramani

2011-01-01

This study investigated the possible interactions between three addition silicone materials (Express®, Aquasil Ultra® and Adsil®), three hemostatic agents (ferric sulfate, StatGel FS®; aluminum sulfate, GelCord®; and aluminum chloride, Hemostop®) and gingival retraction cords previously handled with latex gloves to determine whether direct contact with medicaments or indirect contamination by latex in conditions similar to those found in clinical practice inhibit or affect the setting of the impression materials. A portable device for the simultaneous test of several specimens was specifically developed for this study. Polymerization inhibition was analyzed by examination of the impressions and the molded surface. Ten trials were performed for each addition silicone material used in the study, at a total of 240 study samples. All the samples tested (N=240) were nonreactive regardless of the type of combination used. Aluminum sulfate, ferric sulfate and aluminum chloride hemostatic solutions did not show any inhibitory potential on the addition silicone samples under study, and there were no changes in polymerization as a result of contact between addition silicone and retraction cords handled with latex gloves.

[Hormonal contraception and thromboembolic disease--pathophysiologic findings and practical recommendations].

PubMed

Dulícek, P

2001-09-01

Review the knowledge about changes in hemostatic system in combined oral contraceptives users (focused on studies published between 1997 and 2000). Review of literature. Department of Clinical Hematology, University Hospital Hradec Králové, Czech Republic. Summary of the results of substantial studies published on this topic. Studies were identified by Medline database search. Hemostatic changes were described in all subsystems (in both procoagulant and fibrinolytic systems, in natural inhibitors of coagulation) and could be seen also in molecular marks of coagulation and fibrinolysis activity. Substantial differences were not described for ethinylestradiol doses 20-50 micrograms and up to 1997 also not for different progestins. More expressed acquired resistance to activated protein C at 3rd generation progestins in comparison with levonorgestrel was described recently as well as greater inhibition of fibrinolysis at desogestrel users. The results of recent studies indicate the differences in hemostatic changes between users of 3rd generation progestins, respective desogestrel, and users of levonorgestrel. However, the practical recommendations (aiming at minimalization of VTE risk) are focused on personal and family history and on patient counseling. The choice of progestin could be important but it is not crucial.

The hemostatic effect study of Cirsium setosum on regulating α1-ARs via mediating norepinephrine synthesis by enzyme catalysis.

PubMed

Chang, Nianwei; Li, Yanmei; Zhou, Mengge; Gao, Jie; Hou, Yuanyuan; Jiang, Min; Bai, Gang

2017-03-01

Cirsium setosum (CS) is the aboveground part of Cephalanoplos segetum Kitam. Although it has been used as a hemostatic treatment for thousands of years and is still in use today, the mechanism of CS on regulating ARs is still not clear. In this study, we aimed to clarify the mechanism of CS on regulating ARs. We developed a simple method based on UPLC/Q-TOF MS combined adrenergic receptor dual-luciferase reporter assay systems for the rapid determination of active constituents in CS. The mechanism of tyramine, the main active component for regulating ARs, was further investigated by an in vitro norepinephrine biotransformation test and in vivo vaso activity tests. Two phenethylamine ARs regulators (tyramine and N-methyltyramine) in CS were characterized, and it was found that tyramine could induce vasoconstriction via regulation of α1-ARs by mediating norepinephrine synthesis. The hemostatic effect of CS is associated with tyramine and N-methyltyramine, via regulation of α1-ARs, and the mechanism of tyramine is related to mediating norepinephrine synthesis by enzyme catalysis. Copyright © 2017. Published by Elsevier Masson SAS.

Hemostatic, antibacterial biopolymers from Acacia arabica (Lam.) Willd. and Moringa oleifera (Lam.) as potential wound dressing materials.

PubMed

Bhatnagar, Monica; Parwani, Laxmi; Sharma, Vinay; Ganguli, Jhuma; Bhatnagar, Ashish

2013-10-01

Acacia arabica and Moringa oleifera are credited with a number of medicinal properties. Traditionally gum of Acacia plant is used in the treatment of skin disorders to soothe skin rashes, soreness, inflammation and burns while Moringa seed extracts are known to have antibacterial activity. In the present study the potential of the polymeric component of aqueous extracts of gum acacia (GA) and the seeds of M. oleifera (MSP) in wound management was evaluated. The results revealed that both biopolymers were hemostatic and hasten blood coagulation. They showed shortening of activated partial thromboplastin time and prothrombin time and were non-cytotoxic in nature. Both showed antibacterial activity against organisms known to be involved in wound infections with MIC ranging from 500-600 microg mL(-1) for GA and 300-700 microg mL(-1) for MSP. They were biodegradable and exhibited water absorption capacity in the range of 415 to 935%. The hemostatic character coupled to these properties envisions their potential in preparation of dressings for bleeding and profusely exuding wounds. The biopolymers have been further analysed for their composition by Gas chromatography.

Real-time monitoring of human blood clotting using a lateral excited film bulk acoustic resonator

NASA Astrophysics Data System (ADS)

Chen, Da; Wang, Jingjng; Wang, Peng; Guo, Qiuquan; Zhang, Zhen; Ma, Jilong

2017-04-01

Frequent assay of hemostatic status is an essential issue for the millions of patients using anticoagulant drugs. In this paper, we presented a micro-fabricated film bulk acoustic sensor for the real-time monitoring of blood clotting and the measurement of hemostatic parameters. The device was made of an Au/ZnO/Si3N4 film stack and excited by a lateral electric field. It operated under a shear mode resonance with the frequency of 1.42 GHz and had a quality factor of 342 in human blood. During the clotting process of blood, the resonant frequency decreased along with the change of blood viscosity and showed an apparent step-ladder curve, revealing the sequential clotting stages. An important hemostatic parameter, prothrombin time, was quantitatively determined from the frequency response for different dilutions of the blood samples. The effect of a typical anticoagulant drug (heparin) on the prothrombin time was exemplarily shown. The proposed sensor displayed a good consistency and clinical comparability with the standard coagulometric methods. Thanks to the availability of direct digital signals, excellent potentials of miniaturization and integration, the proposed sensor has promising application for point-of-care coagulation technologies.

Diaminopropionic Acid Reinforced Graphene Sponge and Its Use for Hemostasis.

PubMed

Quan, Kecheng; Li, Guofeng; Tao, Lei; Xie, Qian; Yuan, Qipeng; Wang, Xing

2016-03-01

2,3-Diaminopropionic acid (DapA), a medicinal amino acid, is used for the first time to prepare a DapA cross-linked graphene sponge (DCGS) for hemostasis treatment. In a comparison with the reported ethanediamine (EDA) cross-linked graphene sponge (CGS), this carboxyl-functionalized DCGS can not only quickly absorb plasma, but also stimulate erythrocytes and platelets to change their normal form and structure at the interface, which largely affects a cell's metabolism and biofunction, thus further promoting blood coagulation. Whole blood clotting and rat-tail amputation tests indicated that on the basis of the additional interfacial stimulation, the hemostatic efficiency of the DCGS has been significantly improved in comparison with that of the CGS control (P < 0.05). In-depth insight revealed that the increased oxidation degree and the negative charge density play the crucial rule in the enhanced hemostatic performance. The chiral effect contributes mainly to the selective adhesion of erythrocytes and platelets rather than practical hemostasis. Nevertheless, this presentation demonstrated that, on the premise of keeping the fast absorbability, this is an effective method to improve the hemostatic efficiency by enhancing the cell/graphene interface interaction.

Hemostatic bioactivity of novel Pollen Typhae Carbonisata-derived carbon quantum dots.

PubMed

Yan, Xin; Zhao, Yan; Luo, Juan; Xiong, Wei; Liu, Xiaoman; Cheng, Jinjun; Wang, Yongzhi; Zhang, Meiling; Qu, Huihua

2017-09-05

Pollen Typhae Carbonisata (PTC) is a type of calcined herb drug that has been used as a hemostatic medicine to promote hemostasis for thousands of years. In this study, we discovered and separated novel water-soluble carbon quantum dots (CQDs, named PTC-CQDs) from aqueous extracts of PTC. These PTC-CDs were characterized using transmission electron microscopy (TEM) and high-resolution TEM, as well as Fourier transform infrared, ultraviolet-visible, and fluorescence spectroscopy. Then, we assessed the anti-hemorrhagic effects and related hemostatic mechanisms of the obtained PTC-CQDs. The PTC-CQDs separated from PTC are spherical, monodisperse, and have a narrow size distribution between 2 and 8 nm. In the pharmacology experiment, remarkable anti-hemorrhage effects of PTC-CQDs were revealed. Additionally, the rats showed a profound decrease in activated partial thromboplastin time and increase in fibrinogen and PLT after PTC-CQDs treatment. These results indicated the explicit hemostasis effect of PTC-CQDs, which not only provided a new idea for the material research of PTC, but have also provided new insights into potential biomedical and healthcare applications of CQDs in the field of haemorrhage control and laid a solid foundation for future drug discovery.

Monopolar soft-mode coagulation using hemostatic forceps for peptic ulcer bleeding.

PubMed

Yamasaki, Yasushi; Takenaka, Ryuta; Nunoue, Tomokazu; Kono, Yoshiyasu; Takemoto, Koji; Taira, Akihiko; Tsugeno, Hirofumi; Fujiki, Shigeatsu

2014-01-01

Upper gastrointestinal hemorrhage from bleeding peptic ulcer is sometimes difficult to treat by conventional endoscopic methods. Recently, monopolar electrocoagulation using a soft-coagulation system and hemostatic forceps (soft coagulation) has been used to prevent bleeding during endoscopic submucosal dissection. The aim of this study was to assess the safety and efficacy of soft coagulation in the treatment of bleeding peptic ulcer. A total of 39 patients with peptic ulcers were treated using soft coagulation at our hospital between January 2005 and March 2010. Emergency treatment employed an ERBE soft-mode coagulation system using hemostatic forceps. Second-look endoscopy was performed to evaluate the efficacy of prior therapy. Initial hemostasis was defined as accomplished by soft coagulation, with or without other endoscopic therapy prior to soft coagulation. The rate of initial hemostasis, rebleeding, and ultimate hemostasis were retrospectively analyzed. The study subjects were 31 men and 8 women with a mean age of 68.3±13.7 years, with 29 gastric ulcers and 10 duodenal ulcers. Initial hemostasis was achieved in 37 patients (95%). During follow-up, bleeding recurred in two patients, who were retreated with soft coagulation. The monopolar soft coagulation is feasible and safe for treating bleeding peptic ulcers.

Pre-hospital transfusion of plasma in hemorrhaging trauma patients independently improves hemostatic competence and acidosis.

PubMed

Henriksen, Hanne H; Rahbar, Elaheh; Baer, Lisa A; Holcomb, John B; Cotton, Bryan A; Steinmetz, Jacob; Ostrowski, Sisse R; Stensballe, Jakob; Johansson, Pär I; Wade, Charles E

2016-12-09

The early use of blood products has been associated with improved patient outcomes following severe hemorrhage or traumatic injury. We aimed to investigate the influence of pre-hospital blood products (i.e. plasma and/or RBCs) on admission hemostatic properties and patient outcomes. We hypothesized that pre-hospital plasma would improve hemostatic function as evaluated by rapid thrombelastography (rTEG). We conducted a prospective observational study recruiting 257 trauma patients admitted to a Level I trauma center having received either blood products pre-hospital or in-hospital within 6 hours of admission. Clinical data on patient demographics, blood biochemistry, injury severity score and mortality were collected. Admission rTEG was conducted to characterize the coagulation profile and hemostatic function. 75 patients received pre-hospital plasma and/or RBCs (PH group; nearly half received both RBCs and plasma) whereas 182 patients only received in-hospital blood products (RBCs, Plasma and Platelets) within 6 hours of admission (IH group). PH patients had lower Glasgow coma scale (GCS) scores, more penetrating injuries, lower systolic blood pressures, lower hemoglobin levels, lower platelet counts and greater acidosis upon ED admission than the IH group (all p < 0.05). Despite differences in type of injury and admission vitals indicating that the PH group had more signs of bleeding than the IH group, there were no significant differences in in-hospital mortality (PH 26.7% vs. IH 20.9% p = 0.31). When comparing rTEG variables between PH patients transfused with 0, 1 or 2 units of plasma, more pre-hospital plasma transfusion was tendency towards improved rTEG variables. When adjusting for pre-hospital RBC, pre-hospital plasma was associated with significantly higher rTEG MA (p = 0.012) at hospital admission. After adjusting for pre-hospital RBCs, pre-hospital plasma transfusion was independently associated with increased rTEG MA, as well as arrival indices of shock and hemodynamic instability. Besides more severe injury and worse clinical presentation, the group that received pre-hospital transfusion had early and late mortality similar to patients not transfused pre-hospital. These data suggest that early administration of plasma can provide significant hemostatic and potential survival benefit to severely hemorrhaging trauma patients.

Fluid flows and forces in development: functions, features and biophysical principles

PubMed Central

Freund, Jonathan B.; Goetz, Jacky G.; Hill, Kent L.; Vermot, Julien

2012-01-01

Throughout morphogenesis, cells experience intracellular tensile and contractile forces on microscopic scales. Cells also experience extracellular forces, such as static forces mediated by the extracellular matrix and forces resulting from microscopic fluid flow. Although the biological ramifications of static forces have received much attention, little is known about the roles of fluid flows and forces during embryogenesis. Here, we focus on the microfluidic forces generated by cilia-driven fluid flow and heart-driven hemodynamics, as well as on the signaling pathways involved in flow sensing. We discuss recent studies that describe the functions and the biomechanical features of these fluid flows. These insights suggest that biological flow determines many aspects of cell behavior and identity through a specific set of physical stimuli and signaling pathways. PMID:22395739

Gas Migration Processes through the Gas Hydrate Stability Zone at Four-Way Closure Ridge Offshore SW Taiwan

NASA Astrophysics Data System (ADS)

Kunath, P.; Chi, W. C.; Berndt, C.; Liu, C. S.

2016-12-01

We have used 3D P-Cable seismic data from Four-Way-Closure Ridge, a NW-SE trending anticlinal ridge within the lower slope domain of accretionary wedge, to investigate the geological constraints influencing the fluid migration pattern in the shallow marine sediments. In the seismic data, fluid migration feature manifests itself as high reflection layers of dipping strata, which originate underneath a bottom simulating reflector (BSR) and extend towards the seafloor. Shoaling of the BSR near fluid migration pathways indicates a focused fluid flux, perturbing the temperature field. Furthermore, seafloor video footage confirmed the presence of recent methane seepage above seismically imaged fluid migration pathways. We plan to test two hypotheses for the occurrence of these fluid migration pathways: 1) the extensional regime under the anticlinal ridge crest caused the initiation of localized fault zones, acting as fluid conduits in the gas hydrate stability zone (GHSZ). 2) sediment deformation induced by focused fluid flow and massive growth and dissolution of gas hydrate, similar to processes controlling the evolution of pockmarks on the Nigerian continental margin. We suggest that these processes may be responsible for the formation of a massive hydrate core in the crest of the anticline, as inferred from other geophysical datasets. Triggering process for fluid migration cannot be clearly defined. However, the existence of blind thrust faults may help to advect deep-seated fluids. This may be augmented by biogenic production of shallow gas underneath the ridge, where the excess of gas enables the coexistence of gas, water, and gas hydrate within the GHSZ. Fluid migration structures may exists because of the buoyancy of gas-bearing fluids. This study shows a potential model on how gas-bearing fluids migrate upward towards structural highs, which might occur in other anticlinal structures around the world. Keywords: P-Cable, gas-hydrate, fluid flow, fault-related fold, methane seepage

Gallium nitrate induces fibrinogen flocculation: an explanation for its hemostatic effect?

PubMed

Bauters, A; Holt, D J; Zerbib, P; Rogosnitzky, M

2013-12-01

A novel hemostatic effect of gallium nitrate has recently been discovered. Our aim was to perform a preliminary investigation into its mode of action. Thromboelastography® showed no effect on coagulation but pointed instead to changes in fibrinogen concentration. We measured functional fibrinogen in whole blood after addition of gallium nitrate and nitric acid. We found that gallium nitrate induces fibrinogen precipitation in whole blood to a significantly higher degree than solutions of nitric acid alone. This precipitate is not primarily pH driven, and appears to occur via flocculation. This behavior is in line with the generally observed ability of metals to induce fibrinogen precipitation. Further investigation is required into this novel phenomenon.

Splenic Injury During Percutaneous Nephrolithotomy

PubMed Central

Thomas, Anil A.; Pierce, Gregory; Walsh, R. Matthew; Sands, Mark

2009-01-01

Background: Injury to the spleen is a recognized complication during percutaneous renal access due to the close anatomical relationship of the spleen and the left kidney. However, transsplenic renal access is a rare complication of percutaneous nephrolithotomy and can also result in considerable morbidity, often requiring emergent splenectomy. Methods: We present our experience with splenic injury during percutaneous nephrolithotomy managed conservatively with the use of a collagen-thrombin hemostatic sealant (D-Stat; Vascular Solutions, Inc., Minneapolis, MN) after delayed removal of the nephrostomy tubes. Results: The patient had an uneventful recovery and was discharged home on postoperative day 6. Conclusion: In select hemodynamically stable patients, nonoperative management with the adjunctive use of hemostatic sealants may be considered. PMID:19660224

The effective control of a bleeding injury using a medical adhesive containing batroxobin.

PubMed

You, Kyung Eun; Koo, Min-Ah; Lee, Dae-Hyung; Kwon, Byeong-Ju; Lee, Mi Hee; Hyon, Suong-Hyu; Seomun, Young; Kim, Jong-Tak; Park, Jong-Chul

2014-04-01

Many types of hemostatic agents have been studied for the effective control of bleeding. In this study, a powdery medical adhesive composed of aldehyded dextran and ε-poly (L-lysine) was used with the recombinant batroxobin. Batroxobin is a venomous component from the snake Bothrops atrox moojeni and catalyzes fibrinogen conversion to form soluble fibrin clots. This research aims to examine the performance of the batroxobin-containing adhesive for hemostasis, and evaluate its potential as a novel hemostatic adhesive. The fibrinogen conversion ability of batroxobin was evaluated by a fibrinogen clotting assay and a whole blood clotting assay. Both experiments demonstrated the effectiveness of the batroxobin-containing adhesive for blood clot formation. Animal experiments were also conducted. After a pricking wound was made in an ICR (imprinting control region) mouse liver, the adhesive and various concentrations of batroxobin were applied. The total amount of blood loss was reduced with increasing concentrations of batroxobin. For excessive bleeding conditions, the femoral artery wound model of SD (Sprague-Dawley) rats was adopted. With higher concentrations of batroxobin, hemostasis was more rapidly achieved. Histological analysis of the liver model also supports the hemostatic effects through fibrin clot formation. In conclusion, batroxobin and medical adhesive effectively facilitate blood coagulation, and could be developed for clinical use.

Tissue factor-dependent coagulation activation by heme: A thromboelastometry study.

PubMed

de Souza, Gleice Regina; Hounkpe, Bidossessi Wilfried; Fiusa, Maiara Marx Luz; Colella, Marina Pereira; Annichino-Bizzacchi, Joyce M; Traina, Fabiola; Costa, Fernando Ferreira; De Paula, Erich Vinicius

2017-01-01

Heme has been characterized as potent trigger of inflammation. In hemostasis, although heme has been shown to both induce and inhibit different compartments of hemostasis, its net effect on the hemostatic balance, and the biological relevance of these effects remain to be determined. Herein we evaluated the effect of heme on hemostasis using a global assay able to generate clinically relevant data in several other complex hemostatic diseases. Citrated whole blood samples from healthy participants were stimulated by heme or vehicle and incubated for 4h at 37°C. Rotational thromboelastometry was immediately performed. The participation of tissue factor in coagulation activation was evaluated using inhibitory antibody. Heme was able of inducing ex vivo coagulation activation in whole blood, affecting predominantly parameters associated with the initial phases of clot formation. This activation effect was at least partially dependent on hematopoietic tissue factor, since the effects of heme were partially abrogated by the inhibition of human tissue factor. In conclusion, using a global hemostasis assay, our study confirmed that heme is able to activate coagulation in whole blood, in a tissue factor-dependent way. These findings could explain the disturbance in hemostatic balance observed in conditions associated with the release of heme such as sickle cell disease.

Proteomic and transcriptomic analyses to explain the pleiotropic effects of Ankaferd blood stopper

PubMed Central

Simsek, Cem; Selek, Sebnem; Koca, Meltem; Haznedaroglu, Ibrahim Celal

2017-01-01

Ankaferd blood stopper is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica and has been used as a topical hemostatic agent and with its clinical application established in randomized controlled trials and case reports. Ankaferd has been successfully used in gastrointestinal endobronchial mucosal and cutaneous bleedings and also in abdominal, thoracic, dental and oropharyngeal, and pelvic surgeries. Ankaferd’s hemostatic action is thought to form a protein complex with coagulation factors that facilitate adhesion of blood components. Besides its hemostatic action, Ankaferd has demonstrated pleiotropic effects, including anti-neoplastic and anti-microbial activities and tissue-healing properties; the underlying mechanisms for these have not been well studied. Ankaferd’s individual components were determined by proteomic and chemical analyses. Ankaferd also augments transcription of some transcription factors which is shown with transcriptomic analysis. The independent effects of these ingredients and augmented transcription factors are not known precisely. Here, we review what is known of Ankaferd blood stopper components from chemical, proteomic, and transcriptomic analyses and propose that individual components can explain some pleiotropic effects of Ankaferd. Certainly more research is needed focusing on individual ingredients of Ankaferd to elucidate their precise and effects. PMID:28839937

The effects of a low-dose monophasic preparation of levonorgestrel and ethinyl estradiol on coagulation and other hemostatic factors.

PubMed

Archer, D F; Mammen, E F; Grubb, G S

1999-11-01

This study was undertaken to evaluate the effects on hemostatic factors of a low-dose preparation of levonorgestrel and ethinyl estradiol in a 12-cycle study. Thirty healthy women began taking 100 microg levonorgestrel and 20 microg ethinyl estradiol on the first day of the menstrual cycle, continued to take the preparation for the next 21 days, and then took placebo for 7 days. Mean changes in prothrombin time, partial thromboplastin time, and levels of factors VII and X, antithrombin, plasminogen, fibrinogen, protein S, thrombin-antithrombin complexes, and D-dimer were analyzed at baseline and at cycles 3, 6, and 12 with paired Student t tests. Factor X, plasminogen antigen and activity, and D-dimer levels were significantly increased (P

Hereditary deficiency of the sixth component of complement in man. II. Studies of hemostasis.

PubMed Central

Heusinkveld, R S; Leddy, J P; Klemperer, M R; Breckenridge, R T

1974-01-01

Prompted by previous observations of defective blood clotting in rabbits deficient in the sixth component of complement (C6), an evaluation was made of the hemostatic functions of the homozygous proband of a newly recognized human kindred with hereditary C6 deficiency. This human subject, who had no clinical evidence of a bleeding disorder, exhibited a total lack of C6 by functional and immunoprecipitin assays of serum or plasma. Standard tests of hemostatic function were normal; however, when the whole blood clotting time was measured at 25 degrees C in plastic tubes, it was at the upper range of our normal values. In confirmation of this observation, prothrombin consumption, when performed at 37 degrees C in plastic tubes, was at the lower range of normal. Inulin and endotoxin, in concentrations shown to cause activation of human complement, had little or no effect on clotting times or prothrombin consumption of normal or C6-deficient human blood. These observations indicate that absence of C6 does not have a significant effect on hemostatic function in man. In the light of other investigations, the observed differences in clotting function between C6-deficient human blood and C6-deficient rabbit blood could be due to species differences governing the susceptibility of platelets to complement activation. PMID:11344569

Effects of Chitin and Sepia Ink Hybrid Hemostatic Sponge on the Blood Parameters of Mice

PubMed Central

Zhang, Wei; Sun, Yu-Lin; Chen, Dao-Hai

2014-01-01

Chitin and sepia ink hybrid hemostatic sponge (CTSH sponge), a new biomedical material, was extensively studied for its beneficial biological properties of hemostasis and stimulation of healing. However, studies examining the safety of CTSH sponge in the blood system are lacking. This experiment aimed to examine whether CTSH sponge has negative effect on blood systems of mice, which were treated with a dosage of CTSH sponge (135 mg/kg) through a laparotomy. CTSH sponge was implanted into the abdominal subcutaneous and a laparotomy was used for blood sampling from abdominal aortic. Several kinds of blood parameters were detected at different time points, which were reflected by coagulation parameters including thrombin time (TT), prothrombin time (PT), activated partial thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4); anticoagulation parameter including antithrombin III (AT-III); fibrinolytic parameters including plasminogen (PLG), fibrin degradation product (FDP) and D-dimer; hemorheology parameters including blood viscosity (BV) and plasma viscosity (PV). Results showed that CTSH sponge has no significant effect on the blood parameters of mice. The data suggested that CTSH sponge can be applied in the field of biomedical materials and has potential possibility to be developed into clinical drugs of hemostatic agents. PMID:24727395

Adsorption of tranexamic acid on hydroxyapatite: Toward the development of biomaterials with local hemostatic activity.

PubMed

Sarda, Stéphanie; Errassifi, Farid; Marsan, Olivier; Geffre, Anne; Trumel, Catherine; Drouet, Christophe

2016-09-01

This work proposes to combine tranexamic acid (TAX), a clinically used antifibrinolytic agent, and hydroxyapatite (HA), widely used in bone replacement, to produce a novel bioactive apatitic biomaterial with intrinsic hemostatic properties. The aim of this study was to investigate adsorptive behavior of the TAX molecule onto HA and to point out its release in near physiological conditions. No other phase was observed by X-ray diffraction or transmission electron microscopy, and no apparent change in crystal size was detected. The presence of TAX on the powders was lightly detected on Raman spectra after adsorption. The adsorption data could be fitted with a Langmuir-Freundlich equation, suggesting a strong interaction between adsorbed molecules and the formation of multilayers. The concentration of calcium and phosphate ions in solution remained low and stable during the adsorption process, thus ion exchange during the adsorption process could be ruled out. The release of TAX was fast during the first hours and was governed by a complex process that likely involved both diffusion and dissolution of HA. Preliminary aPTT (activated partial thromboplastin time) hemostasis tests offered promising results for the development of osteoconductive apatitic biomaterials with intrinsic hemostatic properties, whether for dental or orthopedic applications. Copyright © 2016. Published by Elsevier B.V.

Evaluation of thromboelastography in two factor XII-deficient cats.

PubMed

Blois, Shauna L; Holowaychuk, Marie K; Wood, R Darren

2015-01-01

The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency.

Colloidal Confinement of Polyphosphate on Gold Nanoparticles Robustly Activates the Contact Pathway of Blood Coagulation.

PubMed

Szymusiak, Magdalena; Donovan, Alexander J; Smith, Stephanie A; Ransom, Ross; Shen, Hao; Kalkowski, Joseph; Morrissey, James H; Liu, Ying

2016-01-20

Platelet-sized polyphosphate (polyP) was functionalized on the surface of gold nanoparticles (GNPs) via a facile conjugation scheme entailing EDAC (N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride)-catalyzed phosphoramidation of the terminal phosphate of polyP to cystamine. Subsequent reduction of the disulfide moiety allowed for anchoring to the colloidal surface. The ability of the synthesized polyP-GNPs to initiate the contact pathway of clotting in human pooled normal plasma (PNP) was then assayed by quantifying changes in viscous, mechanical, and optical properties upon coagulation. It is revealed that the polyP-GNPs are markedly superior contact activators compared to molecularly dissolved, platelet-sized polyP (of equivalent polymer chain length). Moreover, the particles' capacity to mobilize Factor XII (FXII) and its coactivating proteins appear to be identical to very-long-chain polyP typically found in bacteria. These data imply that nanolocalization of anionic procoagulants on colloidal surfaces, achieved through covalent anchoring, may yield a robust contact surface with the ability to sufficiently cluster active clotting factors together above their threshold concentrations to cease bleeding. The polyP-GNPs therefore serve as a promising foundation in the development of a nanoparticle hemostat to treat a range of hemorrhagic scenarios.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.

PubMed

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 μg+L-NAME; BPC 157 μg+L-arginine, BPC 157 μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

PubMed Central

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

Cost-consequence analysis of different active flowable hemostatic matrices in cardiac surgical procedures.

PubMed

Makhija, D; Rock, M; Xiong, Y; Epstein, J D; Arnold, M R; Lattouf, O M; Calcaterra, D

2017-06-01

A recent retrospective comparative effectiveness study found that use of the FLOSEAL Hemostatic Matrix in cardiac surgery was associated with significantly lower risks of complications, blood transfusions, surgical revisions, and shorter length of surgery than use of SURGIFLO Hemostatic Matrix. These outcome improvements in cardiac surgery procedures may translate to economic savings for hospitals and payers. The objective of this study was to estimate the cost-consequence of two flowable hemostatic matrices (FLOSEAL or SURGIFLO) in cardiac surgeries for US hospitals. A cost-consequence model was constructed using clinical outcomes from a previously published retrospective comparative effectiveness study of FLOSEAL vs SURGIFLO in adult cardiac surgeries. The model accounted for the reported differences between these products in length of surgery, rates of major and minor complications, surgical revisions, and blood product transfusions. Costs were derived from Healthcare Cost and Utilization Project's National Inpatient Sample (NIS) 2012 database and converted to 2015 US dollars. Savings were modeled for a hospital performing 245 cardiac surgeries annually, as identified as the average for hospitals in the NIS dataset. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to test model robustness. The results suggest that if FLOSEAL is utilized in a hospital that performs 245 mixed cardiac surgery procedures annually, 11 major complications, 31 minor complications, nine surgical revisions, 79 blood product transfusions, and 260.3 h of cumulative operating time could be avoided. These improved outcomes correspond to a net annualized saving of $1,532,896. Cost savings remained consistent between $1.3m and $1.8m and between $911k and $2.4m, even after accounting for the uncertainty around clinical and cost inputs, in a one-way and probabilistic sensitivity analysis, respectively. Outcome differences associated with FLOSEAL vs SURGIFLO that were previously reported in a comparative effectiveness study may result in substantial cost savings for US hospitals.

Endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations.

PubMed

Perrault, L P; Menasché, P; Wassef, M; Bidouard, J P; Janiak, P; Villeneuve, N; Jacquemin, C; Bloch, G; Vilaine, J P; Vanhoutte, P M

1996-10-01

Improvements in myocardial protection may include the continuous delivery of normothermic blood cardioplegia. Technical aids are required for optimal visualization of the operative field during the performance of coronary anastomoses if cardioplegia is to be given continuously or during minimally invasive operations. However, the effects of the different hemostatic devices on coronary endothelial function are unknown. We compared the effects on endothelial function of two commonly used hemostatic techniques, coronary clamping and gas jet insufflation, with those of a technique using extravascular balloon occlusion to mimic systolic luminal closure by the surrounding myocardium. The three techniques were applied for 15 minutes on porcine epicardial coronary arteries from explanted hearts. For coronary clamping, standard bulldog clamps were used. Gas jet insufflation was applied by blowing oxygen (12 L/min) tangentially at a 45-degree angle 1 cm away from a 3-mm arteriotomy. Extravascular balloon occlusion was achieved with a needle-tipped silicone loop, the midportion of which, once positioned beneath the coronary artery, was inflated to push a myocardial "cushion" against the back of the vessel until its occlusion. Control rings were taken from the same coronary artery. The endothelial function of control and instrumented arterial rings was then studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Contractions to potassium chloride and prostaglandin F2 alpha and endothelium-independent relaxation to sin-1, a nitric oxide donor, were unaffected in all groups. Endothelium-dependent relaxation to serotonin was impaired after clamping and preserved after gas jet insufflation and extravascular balloon occlusion. Maximal endothelium-dependent relaxation to serotonin was as follows: for coronary clamping, 63% +/- 6% versus 87% +/- 3% in controls; for gas jet insufflation, 67% +/- 12% versus 88% +/- 7%; and for extraluminal balloon occlusion, 79% +/- 6% versus 85% +/- 5%. Whereas commonly used hemostatic devices may impair endothelial function, extravascular balloon occlusion appears to achieve effective hemostasis while preserving endothelial integrity.

Hemostatic properties of the free-electron laser

NASA Astrophysics Data System (ADS)

Cram, Gary P., Jr.; Copeland, Michael L.

1998-09-01

We have investigated the hemostatic properties of the free-electron laser (FEL) and compared these properties to the most commonly used commercial lasers in neurosurgery, CO 2 and Nd:YAG, using an acute canine model. Arterial and venous vessels, of varying diameters from 0.1 to 1.0 mm, were divided with all three lasers. Analysis of five wavelengths of the FEL (3.0, 4.5, 6.1, 6.45, and 7.7 microns) resulted in bleeding without evidence of significant coagulation, regardless of whether the vessel was an artery or vein. Hemorrhage from vessels less than 0.4 mm diameter was subsequently easily controlled with Gelfoam® (topical hemostatic agent) alone, whereas larger vessels required bipolar electrocautery. No significant charring, or contraction of the surrounding parenchyma was noted with any of the wavelengths chosen from FEL source. The CO 2 laser, in continuous mode, easily coagulated vessels with diameters of 4 mm and less, while larger vessels displayed significant bleeding requiring bipolar electrocautery for control. Tissue charring was noted with application of the CO 2 laser. In super pulse mode, the CO 2 laser exhibited similar properties, including significant charring of the surrounding parenchyma. The Nd:YAG coagulated all vessels tested up to 1.4 mm, which was the largest diameter cortical artery found, however this laser displayed significant and extensive contraction and retraction of the surrounding parenchyma. In conclusion, the FEL appears to be a poor hemostatic agent. Our results did not show any benefit of the FEL over current conventional means of achieving hemostasis. However, control of hemorrhage was easily achieved with currently used methods of hemostasis, namely Gelfoam® or bipolar electrocuatery. Although only cortical vessels in dogs were tested, we feel this data can be applied to all animals, including humans, and the peripheral, as well as central, vasculature, as our data on the CO 2 and Nd:YAG appear to closely support previous reports of hemostasis of these two lasers obtained in other models.

Levonorgestrel-Releasing Intrauterine Device Use in Female Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders: Single Institution Review.

PubMed

Adeyemi-Fowode, Oluyemisi A; Santos, Xiomara M; Dietrich, Jennifer E; Srivaths, Lakshmi

2017-08-01

To identify complications and efficacy of the levonorgestrel-releasing intrauterine device (LNgIUD) in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD). A retrospective chart review of 13 postmenarchal adolescent girls with HMB/BD who underwent placement of an LNgIUD. Placement of an LNgIUD. Primary outcome was to identify complications from placement of an LNgIUD. Secondary outcome was to evaluate the efficacy of the LNgIUD in adolescents with BD. Thirteen patients met study criteria. The mean age of diagnosis of HMB was 14.08 ± 1.75 years. BD or bleeding risk factor diagnoses included low von Willebrand (VW) activity in 5, type I VW disease in 5, type IIM VW disease in 1, low VW activity and factor 7 deficiency in 1, and acquired VW disease and factor 7 deficiency in 1. Before LNgIUD placement, other hormonal therapy (n = 13) and hemostatic therapy (antifibrinolytic agents, desmopressin acetate; n = 8) yielded poor control of HMB. The LNgIUD was placed using anesthesia with periprocedure hemostatic therapy with no complications. All patients reported significant improvement in HMB after LNgIUD placement and 60% achieved amenorrhea, with mean time to improvement of 94 ± 69 days. Mean hemoglobin and ferritin levels increased after LNgIUD placement compared with before LNgIUD placement values (P = .02, P = .0085, respectively). Use of supplemental hormonal and hemostatic agents decreased (n = 4) after LNgIUD placement. None required LNgIUD removal; 1 spontaneously expelled the LNgIUD with subsequent replacement. Study results indicated the LNgIUD is an effective therapeutic option in postmenarchal adolescents with HMB due to BD/bleeding risk factor with minimal complications, high compliance rate, improvement in HMB and anemia, and no periprocedural bleeding with hemostatic management. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Do fibrin sealants impact negative outcomes after robot-assisted partial nephrectomy?

PubMed

Cohen, Jason; Jayram, Gautam; Mullins, Jeffrey K; Ball, Mark W; Allaf, Mohamad E

2013-10-01

Contemporary rates of postoperative hemorrhage after partial nephrectomy (PN) are low. Commercially available hemostatic agents are commonly used during this surgery to reduce this risk despite a paucity of data supporting the practice. We assessed the impact of fibrin sealant hemostatic agents, a costly addition to surgeries, during robot-assisted partial nephrectomy (RAPN). Between 2007 and 2011, 114 consecutive patients underwent RAPN by a single surgeon (MEA). Evicel fibrin sealant was used in the first 74 patients during renorraphy. The last 40 patients had renorraphy performed without the use of any hemostatic agents. Clinicopathologic, operative, and complication data were compared between groups. Multivariate and univariate logistic regression analysis was performed to test the association between the use of fibrin sealants and operative outcomes. Patient demographic data and clinical tumor characteristics were similar between groups. The use of fibrin sealant did not increase operative time (166.3 vs 176.1 minutes, P=0.28), warm ischemia time (WIT) (14.4 vs 16.1 minutes, P=0.18), or length of hospital stay (2.6 vs 2.4 days, P=0.35). The omission of these agents did not increase estimated blood loss (116.6 vs 176.1 mL, P=0.8) or postoperative blood transfusion (0% vs 2.5%, P=0.17). Univariate analysis demonstrated no association between use of fibrin sealants and increased complications (P>0.05). Multivariable logistic regression showed no statistically significant predictive value of omission of hemostatic agents for perioperative outcomes (P>0.05). Perioperative hemorrhage and other major complications after contemporary RAPN are rare in experienced hands. In our study, the use of fibrin sealants during RAPN does not decrease the rate of complications, blood loss, or hospital stay. Furthermore, no impact is seen on operative time, WIT, or other negative outcomes. Omitting these agents during RAPN could be a safe, effective, cost-saving measure.

Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor

PubMed Central

Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L.; Kusanovic, Juan Pedro; Munoz, Hernan; Honn, Kenneth V.

2014-01-01

Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography–mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.—Maddipati, K. R., Romero, R., Chaiworapongsa, T., Zhou, S.-L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Munoz, H., Honn, K. V. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor. PMID:25059230

Product comparison model in otolaryngology: Equivalency analysis of absorbable hemostatic agents after endoscopic sinus surgery.

PubMed

Antisdel, Jastin L; Meyer, Annika; Comer, Brett; Jang, David; Gurrola, Jose; Khabbaz, Eyad; Christopher, Kara; Kountakis, Stilianos

2016-01-01

Evidence-based medicine in otolaryngology literature continues to be lacking, especially with regard to new products brought to market. The marketing of products often includes statements of benefit that have limited objective support in research or literature. To address this, and to adequately determine product equivalency/superiority, careful evaluation must be made. In order to establish standards for this process in rhinology products, we directly compare three different absorbable hemostatic agents in patients with chronic rhinosinusitis (CRS) after undergoing endoscopic sinus surgery (ESS), using both objective and subjective outcomes. Double-blinded prospective (level 1) comparison and equivalency analysis of three plant-based absorbable hemostatic agents (carboxymethylcellulose [CMC] gel, mucopolysaccharide hemospheres (MPH), and potato starch wafer) in patients undergoing bilateral ESS. Patients with medically refractory CRS who underwent bilateral ESS were recruited and prospectively followed. At the conclusion of ESS, one of three different hemostatic agents was applied to each nasal passage. Subjective patient data was obtained using rated symptoms compared between the two sides (nasal obstruction, bleeding, pain, and nasal discharge) at baseline and on postoperative days 1, 7, and 14. Objective data was obtained by blinded endoscopic scoring to rate mucosal edema, inflammation, granulation, crusting, infection, and synechiae formation on postoperative weeks 1, 3, and 6. Forty-eight patients who underwent ESS for CRS were included. There is no statistical difference in subjective scores for any of the variables measured, although (MPH) nearly reached statistical significance at postoperative day 7 for increased pain (P = 0.06) and obstruction (P = 0.22). Objective measures showed equivalency between all products, except the CMC gel approached significance at week 3 for increased crusting (P = 0.10), granulation (P = 0.24), and debridement (P = 0.07). At 6 weeks, increased debridement (P = 0.14) also approached significance. Careful and deliberate consideration should be taken when choosing products to assist our surgical endeavors. Subjectively, patients treated with MPH showed near-significant increases in pain and obstruction. In objective measures, CMC gel nearly reaches significance for more postoperative debridement, with increased crusting and inflammation. Product choice could consider these factors, although it remains at the discretion of the surgeon. This model of comparison allows careful product comparison and should be applied to other hemostatics, as well as other materials in use in otolaryngology. 1b. Laryngoscope, 126:S5-S13, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy.

PubMed

Bacyinski, Andrew; Xu, Maosheng; Wang, Wei; Hu, Jiani

2017-01-01

The paravascular pathway, also known as the "glymphatic" pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.

Exploratory Application of Neuropharmacometabolomics in Severe Childhood Traumatic Brain Injury.

PubMed

Hagos, Fanuel T; Empey, Philip E; Wang, Pengcheng; Ma, Xiaochao; Poloyac, Samuel M; Bayır, Hülya; Kochanek, Patrick M; Bell, Michael J; Clark, Robert S B

2018-05-07

To employ metabolomics-based pathway and network analyses to evaluate the cerebrospinal fluid metabolome after severe traumatic brain injury in children and the capacity of combination therapy with probenecid and N-acetylcysteine to impact glutathione-related and other pathways and networks, relative to placebo treatment. Analysis of cerebrospinal fluid obtained from children enrolled in an Institutional Review Board-approved, randomized, placebo-controlled trial of a combination of probenecid and N-acetylcysteine after severe traumatic brain injury (Trial Registration NCT01322009). Thirty-six-bed PICU in a university-affiliated children's hospital. Twelve children 2-18 years old after severe traumatic brain injury and five age-matched control subjects. Probenecid (25 mg/kg) and N-acetylcysteine (140 mg/kg) or placebo administered via naso/orogastric tube. The cerebrospinal fluid metabolome was analyzed in samples from traumatic brain injury patients 24 hours after the first dose of drugs or placebo and control subjects. Feature detection, retention time, alignment, annotation, and principal component analysis and statistical analysis were conducted using XCMS-online. The software "mummichog" was used for pathway and network analyses. A two-component principal component analysis revealed clustering of each of the groups, with distinct metabolomics signatures. Several novel pathways with plausible mechanistic involvement in traumatic brain injury were identified. A combination of metabolomics and pathway/network analyses showed that seven glutathione-centered pathways and two networks were enriched in the cerebrospinal fluid of traumatic brain injury patients treated with probenecid and N-acetylcysteine versus placebo-treated patients. Several additional pathways/networks consisting of components that are known substrates of probenecid-inhibitable transporters were also identified, providing additional mechanistic validation. This proof-of-concept neuropharmacometabolomics assessment reveals alterations in known and previously unidentified metabolic pathways and supports therapeutic target engagement of the combination of probenecid and N-acetylcysteine treatment after severe traumatic brain injury in children.

Method of manufacturing fibrous hemostatic bandages

DOEpatents

Larsen, Gustavo; Spretz, Ruben; Velarde-Ortiz, Raffet

2012-09-04

A method of manufacturing a sturdy and pliable fibrous hemostatic dressing by making fibers that maximally expose surface area per unit weight of active ingredients as a means for aiding in the clot forming process and as a means of minimizing waste of active ingredients. The method uses a rotating object to spin off a liquid biocompatible fiber precursor, which is added at its center. Fibers formed then deposit on a collector located at a distance from the rotating object creating a fiber layer on the collector. An electrical potential difference is maintained between the rotating disk and the collector. Then, a liquid procoagulation species is introduced at the center of the rotating disk such that it spins off the rotating disk and coats the fibers.

RNA-Seq Analysis of Abdominal Fat in Genetically Fat and Lean Chickens Highlights a Divergence in Expression of Genes Controlling Adiposity, Hemostasis, and Lipid Metabolism

PubMed Central

Resnyk, Christopher W.; Chen, Chuming; Huang, Hongzhan; Wu, Cathy H.; Simon, Jean; Le Bihan-Duval, Elisabeth; Duclos, Michel J.; Cogburn, Larry A.

2015-01-01

Genetic selection for enhanced growth rate in meat-type chickens (Gallus domesticus) is usually accompanied by excessive adiposity, which has negative impacts on both feed efficiency and carcass quality. Enhanced visceral fatness and several unique features of avian metabolism (i.e., fasting hyperglycemia and insulin insensitivity) mimic overt symptoms of obesity and related metabolic disorders in humans. Elucidation of the genetic and endocrine factors that contribute to excessive visceral fatness in chickens could also advance our understanding of human metabolic diseases. Here, RNA sequencing was used to examine differential gene expression in abdominal fat of genetically fat and lean chickens, which exhibit a 2.8-fold divergence in visceral fatness at 7 wk. Ingenuity Pathway Analysis revealed that many of 1687 differentially expressed genes are associated with hemostasis, endocrine function and metabolic syndrome in mammals. Among the highest expressed genes in abdominal fat, across both genotypes, were 25 differentially expressed genes associated with de novo synthesis and metabolism of lipids. Over-expression of numerous adipogenic and lipogenic genes in the FL chickens suggests that in situ lipogenesis in chickens could make a more substantial contribution to expansion of visceral fat mass than previously recognized. Distinguishing features of the abdominal fat transcriptome in lean chickens were high abundance of multiple hemostatic and vasoactive factors, transporters, and ectopic expression of several hormones/receptors, which could control local vasomotor tone and proteolytic processing of adipokines, hemostatic factors and novel endocrine factors. Over-expression of several thrombogenic genes in abdominal fat of lean chickens is quite opposite to the pro-thrombotic state found in obese humans. Clearly, divergent genetic selection for an extreme (2.5–2.8-fold) difference in visceral fatness provokes a number of novel regulatory responses that govern growth and metabolism of visceral fat in this unique avian model of juvenile-onset obesity and glucose-insulin imbalance. PMID:26445145

Peritoneal fluid transport in CAPD patients with different transport rates of small solutes.

PubMed

Sobiecka, Danuta; Waniewski, Jacek; Weryński, Andrzej; Lindholm, Bengt

2004-01-01

Continuous ambulatory peritoneal dialysis (CAPD) patients with high peritoneal solute transport rate often have inadequate peritoneal fluid transport. It is not known whether this inadequate fluid transport is due solely to a too rapid fall of osmotic pressure, or if the decreased effectiveness of fluid transport is also a contributing factor. To analyze fluid transport parameters and the effectiveness of dialysis fluid osmotic pressure in the induction of fluid flow in CAPD patients with different small solute transport rates. 44 CAPD patients were placed in low (n = 6), low-average (n = 13), high-average (n = 19), and high (n = 6) transport groups according to a modified peritoneal equilibration test (PET). The study involved a 6-hour peritoneal dialysis dwell with 2 L 3.86% glucose dialysis fluid for each patient. Radioisotopically labeled serum albumin was added as a volume marker.The fluid transport parameters (osmotic conductance and fluid absorption rate) were estimated using three mathematical models of fluid transport: (1) Pyle model (model P), which describes ultrafiltration rate as an exponential function of time; (2) model OS, which is based on the linear relationship of ultrafiltration rate and overall osmolality gradient between dialysis fluid and blood; and (3) model G, which is based on the linear relationship between ultrafiltration rate and glucose concentration gradient between dialysis fluid and blood. Diffusive mass transport coefficients (K(BD)) for glucose, urea, creatinine, potassium, and sodium were estimated using the modified Babb-Randerson-Farrell model. The high transport group had significantly lower dialysate volume and glucose and osmolality gradients between dialysate and blood, but significantly higher K(BD) for small solutes compared with the other transport groups. Osmotic conductance, fluid absorption rate, and initial ultrafiltration rate did not differ among the transport groups for model OS and model P. Model G yielded unrealistic values of fluid transport parameters that differed from those estimated by models OS and P. The K(BD) values for small solutes were significantly different among the groups, and did not correlate with fluid transport parameters for model OS. The difference in fluid transport between the different transport groups was due only to the differences in the rate of disappearance of the overall osmotic pressure of the dialysate, which was a combined result of the transport rate of glucose and other small solutes. Although the glucose gradient is the major factor influencing ultrafiltration rate, other solutes, such as urea, are also of importance. The counteractive effect of plasma small solutes on transcapillary ultrafiltration was found to be especially notable in low transport patients. Thus, glucose gradient alone should not be considered the only force that shapes the ultrafiltration profile during peritoneal dialysis. We did not find any correlations between diffusive mass transport coefficients for small solutes and fluid transport parameters such as osmotic conductance or fluid and volume marker absorption. We may thus conclude that the pathway(s) for fluid transport appears to be partly independent from the pathway(s) for small solute transport, which supports the hypothesis of different pore types for fluid and solute transport.

Fibrinolytic and procoagulant activities of Yersinia pestis and Salmonella enterica.

PubMed

Korhonen, T K

2015-06-01

Pla of the plague bacterium Yersinia pestis and PgtE of the enteropathogen Salmonella enterica are surface-exposed, transmembrane β-barrel proteases of the omptin family that exhibit a complex array of interactions with the hemostatic systems in vitro, and both proteases are established virulence factors. Pla favors fibrinolysis by direct activation of plasminogen, inactivation of the serpins plasminogen activator inhibitor-1 and α2-antiplasmin, inactivation of the thrombin-activable fibrinolysis inhibitor, and activation of single-chain urokinase. PgtE is structurally very similar but exhibits partially different functions and differ in expression control. PgtE proteolysis targets control aspects of fibrinolysis, and mimicry of matrix metalloproteinases enhances cell migration that should favor the intracellular spread of the bacterium. Enzymatic activity of both proteases is strongly influenced by the environment-induced variations in lipopolysaccharide that binds to the β-barrel. Both proteases cleave the tissue factor pathway inhibitor and thus also express procoagulant activity. © 2015 International Society on Thrombosis and Haemostasis.

Dynamic fluid connectivity during steady-state multiphase flow in a sandstone.

PubMed

Reynolds, Catriona A; Menke, Hannah; Andrew, Matthew; Blunt, Martin J; Krevor, Samuel

2017-08-01

The current conceptual picture of steady-state multiphase Darcy flow in porous media is that the fluid phases organize into separate flow pathways with stable interfaces. Here we demonstrate a previously unobserved type of steady-state flow behavior, which we term "dynamic connectivity," using fast pore-scale X-ray imaging. We image the flow of N 2 and brine through a permeable sandstone at subsurface reservoir conditions, and low capillary numbers, and at constant fluid saturation. At any instant, the network of pores filled with the nonwetting phase is not necessarily connected. Flow occurs along pathways that periodically reconnect, like cars controlled by traffic lights. This behavior is consistent with an energy balance, where some of the energy of the injected fluids is sporadically converted to create new interfaces.

Abnormal placentation.

PubMed

Bauer, Samuel T; Bonanno, Clarissa

2009-04-01

Abnormal placentation poses a diagnostic and treatment challenge for all providers caring for pregnant women. As one of the leading causes of postpartum hemorrhage, abnormal placentation involves the attachment of placental villi directly to the myometrium with potentially deeper invasion into the uterine wall or surrounding organs. Surgical procedures that disrupt the integrity of uterus, including cesarean section, dilatation and curettage, and myomectomy, have been implicated as key risk factors for placenta accreta. The diagnosis is typically made by gray-scale ultrasound and confirmed with magnetic resonance imaging, which may better delineate the extent of placental invasion. It is critical to make the diagnosis before delivery because preoperative planning can significantly decrease blood loss and avoid substantial morbidity associated with placenta accreta. Aggressive management of hemorrhage through the use of uterotonics, fluid resuscitation, blood products, planned hysterectomy, and surgical hemostatic agents can be life-saving for these patients. Conservative management, including the use of uterine and placental preservation and subsequent methotrexate therapy or pelvic artery embolization, may be considered when a focal accreta is suspected; however, surgical management remains the current standard of care.

Single-molecule force measurements of the polymerizing dimeric subunit of von Willebrand factor

NASA Astrophysics Data System (ADS)

Wijeratne, Sithara S.; Li, Jingqiang; Yeh, Hui-Chun; Nolasco, Leticia; Zhou, Zhou; Bergeron, Angela; Frey, Eric W.; Moake, Joel L.; Dong, Jing-fei; Kiang, Ching-Hwa

2016-01-01

Von Willebrand factor (VWF) multimers are large adhesive proteins that are essential to the initiation of hemostatic plugs at sites of vascular injury. The binding of VWF multimers to platelets, as well as VWF proteolysis, is regulated by shear stresses that alter VWF multimeric conformation. We used single molecule manipulation with atomic force microscopy (AFM) to investigate the effect of high fluid shear stress on soluble dimeric and multimeric forms of VWF. VWF dimers are the smallest unit that polymerizes to construct large VWF multimers. The resistance to mechanical unfolding with or without exposure to shear stress was used to evaluate VWF conformational forms. Our data indicate that, unlike recombinant VWF multimers (RVWF), recombinant dimeric VWF (RDVWF) unfolding force is not altered by high shear stress (100 dynes/cm2 for 3 min at 37°C ). We conclude that under the shear conditions used (100 dynes/cm2 for 3 min at 37°C ) , VWF dimers do not self-associate into a conformation analogous to that attained by sheared large VWF multimers.

Hemostasis in the Very Young.

PubMed

Kenet, Gili; Barg, Assaf Arie; Nowak-Göttl, Ulrike

2018-06-18

Hemostasis is a dynamic process that starts in utero. The coagulation system evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins in early life compared with adulthood. This concept, known as "developmental hemostasis," has important biological and clinical implications. Overall, impaired platelet function, along with physiologically reduced levels of vitamin K-dependent and contact coagulation factors, may cause poorer clot firmness even in healthy neonates. However, increased activity of von Willebrand factor and low levels of coagulation inhibitors that promote hemostasis counterbalance the delicate and immature hemostatic system. Since this hemostatic system has little reserve capacity, preterm neonates or sick infants are extremely vulnerable and predisposed to either hemorrhagic or thrombotic complications. This review will address the concept and manifestations of developmental hemostasis with respect to clinical disease phenotypes. It will discuss bleeding diagnosis in neonates, dealing especially with the devastating complications of intracerebral and pulmonary hemorrhage in preterm infants. Neonates, especially the sickest preterm ones, are also extremely susceptible to thrombotic complications; thus, thrombosis in neonates will be reviewed, with special focus on arterial ischemic perinatal stroke. Based on the concept of developmental hemostasis, the phenotypes of clinically relevant bleeding or thrombotic disorders among neonates may differ from those of older infants and children. Treatment options for these conditions will be suggested and reviewed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential.

PubMed

Zouari Bouassida, Karama; Bardaa, Sana; Khimiri, Meriem; Rebaii, Tarek; Tounsi, Slim; Jlaiel, Lobna; Trigui, Mohamed

2017-01-01

The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H 2 OE), showing the most potent antibacterial and antioxidant activities in vitro , thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, "CICAFLORA," and U. dioica EtOH-H 2 OE (50  µ L/mm 2 ) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H 2 OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding ( P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H 2 OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H 2 OE in wound healing and supported its traditional use.

Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry.

PubMed

Baudo, Francesco; Collins, Peter; Huth-Kühne, Angela; Lévesque, Hervé; Marco, Pascual; Nemes, László; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul

2012-07-05

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

Massive oral bleeding after full-mouth extraction in a patient with B-cell lymphocytic leukemia/small lymphocytic lymphoma reversed with recombinant activated factor VII.

PubMed

Sprenker, Collin; Omar, Hesham R; Powless, R Andrew; Mangar, Devanand; Camporesi, Enrico

2016-02-01

Full-mouth extraction can be associated with intraoral bleeding, which usually is controlled with local hemostatic measures. Recombinant activated factor VII (rFVIIa) occasionally is used to stop bleeding in a variety of off-label indications, with the main argument curtailing its use being thrombotic events. The authors describe the use of rFVIIa for bleeding after full-mouth extraction in a patient with undiagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. A 72-year-old man underwent full-mouth extraction (18 teeth). The next day, the patient experienced massive oral bleeding. The authors administered tranexamic acid, aminocaproic acid, and a total of 12 units of packed red blood cells in addition to local hemostatic measures without control of bleeding. On postoperative day 10, the authors administered 5,000 micrograms of rFVIIa, and within 2 hours oral the bleeding ceased. The authors performed flow cytometry and diagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. Unexplained massive oral bleeding despite adequate local hemostatic measures should prompt further investigations for underlying bleeding or coagulation disorders. The authors describe the successful use of rFVIIa in massive oral bleeding. Further studies are mandatory to study the effectiveness of this drug for this off-label indication. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential

PubMed Central

Bardaa, Sana; Khimiri, Meriem; Rebaii, Tarek; Jlaiel, Lobna

2017-01-01

The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H2OE), showing the most potent antibacterial and antioxidant activities in vitro, thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, “CICAFLORA,” and U. dioica EtOH-H2OE (50 µL/mm2) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H2OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding (P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H2OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H2OE in wound healing and supported its traditional use. PMID:29201895

Evaluation of thromboelastography in two factor XII-deficient cats

PubMed Central

Holowaychuk, Marie K; Wood, R Darren

2015-01-01

Case summary The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. Relevance and novel information TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency. PMID:28491358

Fluid pathways from mantle wedge up to forearc seafloor in the coseismic slip area of the 2011 Tohoku earthquake

NASA Astrophysics Data System (ADS)

Park, J. O.; Tsuru, T.; Fujie, G.; Kagoshima, T.; Sano, Y.

2017-12-01

A lot of fluids at subduction zones are exchanged between the solid Earth and ocean, affecting the earthquake and tsunami generation. New multi-channel seismic reflection and sub-bottom profiling data reveal normal and reverse faults as the fluid pathways in the coseismic slip area of the 2011 Tohoku earthquake (M9.0). Based on seismic reflection characteristics and helium isotope anomalies, we recognize variations in fluid pathways (i.e., faults) from the mantle wedge up to forearc seafloor in the Japan Trench margin. Some fluids are migrated from the mantle wedge along plate interface and then normal or reverse faults cutting through the overriding plate. Others from the mantle wedge are migrated directly up to seafloor along normal faults, without passing through the plate interface. Locations of the normal faults are roughly consistent with aftershocks of the 2011 Tohoku earthquake, which show focal mechanism of normal faulting. It is noticeable that landward-dipping normal faults developing down into Unit C (Cretaceous basement) from seafloor are dominant in the middle slope region where basal erosion is inferred to be most active. A high-amplitude, reverse-polarity reflection of the normal faults within Unit C suggests that the fluids are locally trapped along the faults in high pore pressures. The 2011 Tohoku mainshock and subsequent aftershocks could lead the pre-existing normal faults to be reactive and more porous so that the trapped fluids are easily transported up to seafloor through the faults. Elevated fluid pressures can decrease the effective normal stress for the fault plane, allowing easier slip of the landward-dipping normal fault and also enhancing its tsunamigenic potential.

The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy

PubMed Central

Bacyinski, Andrew; Xu, Maosheng; Wang, Wei; Hu, Jiani

2017-01-01

The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted. PMID:29163074

Newer Hemostatic Agents Used in the Practice of Dermatologic Surgery

PubMed Central

Brewer, Jerry D.

2013-01-01

Minor postoperative bleeding is the most common complication of cutaneous surgery. Because of the commonality of this complication, hemostasis is an important concept to address when considering dermatologic procedures. Patients that have a bleeding diathesis, an inherited/acquired coagulopathy, or who are on anticoagulant/antiplatelet medications pose a greater risk for bleeding complications during the postoperative period. Knowledge of these conditions preoperatively is of the utmost importance, allowing for proper preparation and prevention. Also, it is important to be aware of the various hemostatic modalities available, including electrocoagulation, which is among the most effective and widely used techniques. Prompt recognition of hematoma formation and knowledge of postoperative wound care can prevent further complications such as wound dehiscence, infection, or skin-graft necrosis, minimizing poor outcomes. PMID:23997764

Proteome analysis of snake venom toxins: pharmacological insights.

PubMed

Georgieva, Dessislava; Arni, Raghuvir K; Betzel, Christian

2008-12-01

Snake venoms are an extremely rich source of pharmacologically active proteins with a considerable clinical and medical potential. To date, this potential has not been fully explored, mainly because of our incomplete knowledge of the venom proteome and the pharmacological properties of its components, in particular those devoid of enzymatic activity. This review summarizes the latest achievements in the determination of snake venom proteome, based primarily on the development of new strategies and techniques. Detailed knowledge of the venom toxin composition and biological properties of the protein constituents should provide the scaffold for the design of new more effective drugs for the treatment of the hemostatic system and heart disorders, inflammation, cancer and consequences of snake bites, as well as new tools for clinical diagnostic and assays of hemostatic parameters.

Comparison of functional aspects of the coagulation cascade in human and sea turtle plasmas.

PubMed

Soslau, Gerald; Wallace, Bryan; Vicente, Catherine; Goldenberg, Seth J; Tupis, Todd; Spotila, James; George, Robert; Paladino, Frank; Whitaker, Brent; Violetta, Gary; Piedra, Rotney

2004-08-01

Functional hemostatic pathways are critical for the survival of all vertebrates and have been evolving for more than 400 million years. The overwhelming majority of studies of hemostasis in vertebrates have focused on mammals with very sparse attention paid to reptiles. There have been virtually no studies of the coagulation pathway in sea turtles whose ancestors date back to the Jurassic period. Sea turtles are often exposed to rapidly altered environmental conditions during diving periods. This may reduce their blood pH during prolonged hypoxic dives. This report demonstrates that five species of turtles possess only one branch of the mammalian coagulation pathway, the extrinsic pathway. Mixing studies of turtle plasmas with human factor-deficient plasmas indicate that the intrinsic pathway factors VIII and IX are present in turtle plasma. These two factors may play a significant role in supporting the extrinsic pathway by feedback loops. The intrinsic factors, XI and XII are not detected which would account for the inability of reagents to induce coagulation via the intrinsic pathway in vitro. The analysis of two turtle factors, factor II (prothrombin) and factor X, demonstrates that they are antigenically/functionally similar to the corresponding human factors. The turtle coagulation pathway responds differentially to both pH and temperature relative to each turtle species and relative to human samples. The coagulation time (prothrombin time) increases as the temperature decreases between 37 and 15 degrees C. The increased time follows a linear relationship, with similar slopes for loggerhead, Kemps ridley and hawksbill turtles as well as for human samples. Leatherback turtle samples show a dramatic nonlinear increased time below 23 degrees C, and green turtle sample responses were similar but less dramatic. All samples also showed increased prothrombin times as the pH decreased from 7.8 to 6.4, except for three turtle species. The prothrombin times decreased, to varying extents, in a linear fashion relative to reduced pH with the rate of change greatest in leatherbacks>green>loggerhead turtles. All studies were conducted with reagents developed for human samples which would impact on the quantitative results with the turtle samples, but are not likely to alter the qualitative results. These comparative studies of the coagulation pathway in sea turtles and humans could enhance our knowledge of structure/function relationships and evolution of coagulation factors.

Vascular basement membranes as pathways for the passage of fluid into and out of the brain.

PubMed

Morris, Alan W J; Sharp, Matthew MacGregor; Albargothy, Nazira J; Fernandes, Rute; Hawkes, Cheryl A; Verma, Ajay; Weller, Roy O; Carare, Roxana O

2016-05-01

In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways

NASA Technical Reports Server (NTRS)

McAllister, T. N.; Frangos, J. A.

1999-01-01

Fluid flow has been shown to be a potent stimulus in osteoblasts and osteocytes and may therefore play an important role in load-induced bone remodeling. The objective of this study was to investigate the characteristics of flow-activated pathways. Previously we reported that fluid flow stimulates rapid and continuous release of nitric oxide (NO) in primary rat calvarial osteoblasts. Here we demonstrate that flow-induced NO release is mediated by shear stress and that this response is distinctly biphasic. Transients in shear stress associated with the onset of flow stimulated a burst in NO production (8.2 nmol/mg of protein/h), while steady flow stimulated sustained NO production (2.2 nmol/mg of protein/h). Both G-protein inhibition and calcium chelation abolished the burst phase but had no effect on sustained production. Activation of G-proteins stimulated dose-dependent NO release in static cultures of both calvarial osteoblasts and UMR-106 osteoblast-like cells. Pertussis toxin had no effect on NO release. Calcium ionophore stimulated low levels of NO production within 15 minutes but had no effect on sustained production. Taken together, these data suggest that fluid shear stress stimulates NO release by two distinct pathways: a G-protein and calcium-dependent phase sensitive to flow transients, and a G-protein and calcium-independent pathway stimulated by sustained flow.

Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor.

PubMed

Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L; Kusanovic, Juan Pedro; Munoz, Hernan; Honn, Kenneth V

2014-11-01

Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography-mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition. © FASEB.

Supercritical Fuel Pyrolysis

DTIC Science & Technology

2010-05-30

supercritical fluids . These temperatures and pressures will also cause the fuel to undergo pyrolytic reactions, which have the potential of forming...With regard to physical properties, supercritical fluids have highly variable densities, no surface tension, and transport properties (i.e., mass...effects in supercritical fluids , often affecting chemical reaction pathways by facilitating the formation of certain transition states [6]. Because

Pathway from subducting slab to surface for melt and fluids beneath Mount Rainier.

PubMed

McGary, R Shane; Evans, Rob L; Wannamaker, Philip E; Elsenbeck, Jimmy; Rondenay, Stéphane

2014-07-17

Convergent margin volcanism originates with partial melting, primarily of the upper mantle, into which the subducting slab descends. Melting of this material can occur in one of two ways. The flow induced in the mantle by the slab can result in upwelling and melting through adiabatic decompression. Alternatively, fluids released from the descending slab through dehydration reactions can migrate into the hot mantle wedge, inducing melting by lowering the solidus temperature. The two mechanisms are not mutually exclusive. In either case, the buoyant melts make their way towards the surface to reside in the crust or to be extruded as lava. Here we use magnetotelluric data collected across the central state of Washington, USA, to image the complete pathway for the fluid-melt phase. By incorporating constraints from a collocated seismic study into the magnetotelluric inversion process, we obtain superior constraints on the fluids and melt in a subduction setting. Specifically, we are able to identify and connect fluid release at or near the top of the slab, migration of fluids into the overlying mantle wedge, melting in the wedge, and transport of the melt/fluid phase to a reservoir in the crust beneath Mt Rainier.

Pathway from subducting slab to surface for melt and fluids beneath Mount Rainier

NASA Astrophysics Data System (ADS)

McGary, R. Shane; Evans, Rob L.; Wannamaker, Philip E.; Elsenbeck, Jimmy; Rondenay, Stéphane

2014-07-01

Convergent margin volcanism originates with partial melting, primarily of the upper mantle, into which the subducting slab descends. Melting of this material can occur in one of two ways. The flow induced in the mantle by the slab can result in upwelling and melting through adiabatic decompression. Alternatively, fluids released from the descending slab through dehydration reactions can migrate into the hot mantle wedge, inducing melting by lowering the solidus temperature. The two mechanisms are not mutually exclusive. In either case, the buoyant melts make their way towards the surface to reside in the crust or to be extruded as lava. Here we use magnetotelluric data collected across the central state of Washington, USA, to image the complete pathway for the fluid-melt phase. By incorporating constraints from a collocated seismic study into the magnetotelluric inversion process, we obtain superior constraints on the fluids and melt in a subduction setting. Specifically, we are able to identify and connect fluid release at or near the top of the slab, migration of fluids into the overlying mantle wedge, melting in the wedge, and transport of the melt/fluid phase to a reservoir in the crust beneath Mt Rainier.

Alteration of Hemostatic Parameters in Patients with Different Levels of Subclinical Hypothyroidism and the Effect of L-thyroxine Treatment.

PubMed

Gao, Fang; Wang, Guangya; Xu, Jinxiu

2017-01-01

Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 μIU/mL

Day care PNL using 'Santosh-PGI hemostatic seal' versus standard PNL: A randomized controlled study.

PubMed

Kumar, Santosh; Singh, Shivanshu; Singh, Prashant; Singh, Shrawan Kumar

2016-01-01

To compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL. It was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery. A total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 ±0.68 vs. 1.30 ±0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 ±1.23 vs. 6.12 ±0.96, 1.48 ±0.50 vs. 4.09 ±1.11 grams and 0.48 ±0.26 vs. 4.74 ±1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 ±3.05 vs.18.42 ±4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21). Tubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission.

Day care PNL using ‘Santosh-PGI hemostatic seal’ versus standard PNL: A randomized controlled study

PubMed Central

Singh, Shivanshu; Singh, Prashant; Singh, Shrawan Kumar

2016-01-01

Introduction To compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL. Material and methods It was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery. Results A total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 ±0.68 vs. 1.30 ±0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 ±1.23 vs. 6.12 ±0.96, 1.48 ±0.50 vs. 4.09 ±1.11 grams and 0.48 ±0.26 vs. 4.74 ±1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 ±3.05 vs.18.42 ±4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21). Conclusions Tubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission. PMID:27551557

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables.

PubMed

Endrikat, Jan; Klipping, C; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

2002-03-01

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers. In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.

Upon admission coagulation and platelet function in patients with thermal and electrical injuries.

PubMed

Wade, Charles E; Baer, Lisa A; Cardenas, Jessica C; Folkerson, Lindley E; Nutall-Aurora, Kisha; Cotton, Bryan A; Matijevic, Nena; Holcomb, John B; Cross, James M; Huzar, Todd

2016-12-01

There has been increased focus on hemostatic potential and function in the initial assessment of the patient with traumatic injuries, that not been extensively studied in patients with burns. We proposed to determine the hemostatic potential of patients with burns upon admission to the emergency department and contrasted their condition with that of healthy controls and patients with other traumatic injuries. In addition we assessed differences due to thermal versus electrical injury and evaluated the effect of burn size. This is a patient based prospective observational study conducted with delayed consented. Subjects at the highest level of trauma activation upon admission to the ED had a blood sample collected for research purposes and were subsequently consented. Hemostatic potential was measured by rapid thromelastography (r-TEG ® ), thrombin generation by calibrated automated thrombogram (CAT) and platelet function by Multiplate ® using five activators. Burn subjects were compared to subjects with other traumatic injuries and controls. Within the burn subjects additional analysis compared mechanism (thermal vs. electrical) and burn size. Values are medians (IQR). Two hundred and eighty two trauma patients (with burns n=40, 14%) and 27 controls were enrolled. Upon admission, compared to controls, subjects with burns or trauma were hyper-coagulable based on r-TEG and CAT, with increased rates of clot formation and thrombin generation. There were no differences in burns compared to other traumatic injuries. The presence of hyper-coagulation did not appear to be related to the type of burn or the percentage of total body surface area involved. Employing previous defined cut points for R-TEG driven therapeutic interventions burn patients had similar rates of hyper- and hypo-coagulation noted in patients with traumatic injuries. Upon admission patients with burns are in a hyper-coagulable state similar to that of other trauma patients. Employing demonstrated cut points of hemostatic potential in trauma patients associated with increased risk of poor outcomes demonstrated the incidence in burn patients to be similar, suggesting that these values could be used in the early assessment of the patient with burns to guide treatment interventions. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

How to optimize the economic viability of thyroid surgery in a French public hospital?

PubMed

D'Hubert, E; Proske, J-M

2010-08-01

Physicians in France have been asked to change their day-to-day medical practice to reduce overall costs. We examine ways to achieve this goal in thyroid surgery. We defined and implemented a clinical pathway to optimize the economic viability of thyroid surgery by increasing revenues and lowering expenses. An increase in revenue was achieved by decreasing patient length of stay (LOS) through the use of a fast-track rehabilitation protocol. Expenses were decreased by performing all pre-operative work-up in the out-patient setting and by decreasing costs in the operating room. For 292 consecutive patients who underwent thyroidectomy, the average LOS has been decreased over time to a mean of 2.03 days in 2008; 96% of patients were discharged on the first postoperative day. These results were primarily achieved by using a fast-track rehabilitation clinical pathway, and no increase in postoperative morbidity was noted. Operating time was decreased by 20% through the use of a second surgical assistant and hemostatic scissors but this improvement did not translate into better daily utilization of the operating room. The economic profitability of thyroid surgery is improved when mean LOS is reduced to 2 days through a fast-track protocol. Decreasing the duration of hospitalization was more effective than decreasing operative duration in controlling overall costs. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Anaerobic Biodegradation of Ethylene Glycol within Hydraulic Fracturing Fluid

NASA Astrophysics Data System (ADS)

Heyob, K. M.; Mouser, P. J.

2014-12-01

Ethylene glycol (EG) is a commonly used organic additive in hydraulic fracturing fluids used for shale gas recovery. Under aerobic conditions, this compound readily biodegrades to acetate and CO2 or is oxidized through the glycerate pathway. In the absence of oxygen, organisms within genera Desulfovibrio, Acetobacterium, and others can transform EG to acetaldehyde, a flammable and suspected carcinogenic compound. Acetaldehyde can then be enzymatically degraded to ethanol or acetate and CO2. However, little is known on how EG degrades in the presence of other organic additives, particularly under anaerobic conditions representative of deep groundwater aquifers. To better understand the fate and attenuation of glycols within hydraulic fracturing fluids we are assessing their biodegradation potential and pathways in batch anaerobic microcosm treatments. Crushed Berea sandstone was inoculated with groundwater and incubated with either EG or a synthetic fracturing fluid (SFF) containing EG formulations. We tracked changes in dissolved organic carbon (DOC), EG, and its transformation products over several months. Approximately 41% of bulk DOC in SFF is degraded within 21 days, with 58% DOC still remaining after 63 days. By comparison, this same SFF degrades by 70% within 25 days when inoculated with sediment-groundwater microbial communities, suggesting that bulk DOC degradation occurs at a slower rate and to a lesser extent with bedrock. Aerobic biodegradation of EG occurs rapidly (3-7 days); however anaerobic degradation of EG is much slower, requiring several weeks for substantial DOC loss to be observed. Ongoing experiments are tracking the degradation pathways of EG alone and in the presence of SFF, with preliminary data showing incomplete glycol transformation within the complex hydraulic fracturing fluid mixture. This research will help to elucidate rates, processes, and pathways for EG biodegradation and identify key microbial taxa involved in its degradation.

Metastasis: recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin.

PubMed

Alonso, D F; Ripoll, G V; Garona, J; Iannucci, N B; Gomez, D E

2011-11-01

Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.

Comparison of Floseal(r) and electrocautery in hemostasis after total knee arthroplasty

PubMed Central

Helito, Camilo Partezani; Gobbi, Riccardo Gomes; Castrillon, Lucas Machado; Hinkel, Betina Bremer; Pécora, José Ricardo; Camanho, Gilberto Luis

2013-01-01

Objective To evaluate whether hemostasis with eletrocauterization in comparison with Floseal(r) leads to different bleeding rates during total knee arthroplasty. Methods A comparative study was performed between two groups: group with ten consecutive total knee arthroplasties with Floseal(r) used as hemostatic method and control group with ten consecutive total knee arthroplasties with eletrocauterization as hemostatic method. Bleeding parameters such as debit of the drain, liquid infusion and blood transfusion rate were recorded. Results Floseal(r) group received less blood transfusion, less liquid infusion and lower drainage in absolute numbers compared to the control group. However, no parameter was statistically significant. Conclusion Hemostasis with Floseal(r) is as effective as hemostasis with eletrocauterization, what makes it a viable alternative to patients with contraindication to electric scalpel use. Level of Evidence II, Prospective Comparative Study. PMID:24453689

Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Dijkstra, Bas; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Owens, Sean D; Hass, Carlyle; Kass, Philip H; Paul-Murphy, Joanne R

2015-04-01

To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). 12 Hispaniolan Amazon parrots. Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-β-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

2018-01-01

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

[Absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together to cure epistaxis with blood disease].

PubMed

Liu, Hua; Gao, Zhanmei; Song, Yang; Lu, Mancun

2014-01-01

This study investigated the effects and Numerical Rating Pain Scale (NRS) of using absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together nasal packing in the control of epistaxis with blood disease, and compared it with traditional vaseline gauze. Ninety-six blood disease patient with epistaxis were enrolled between January 2009 and February 2011, they were divided into two groups at random, and differently treated with absorbable shanching satin rb-bFGF prepreg sheet and the vaseline gauze nasal packing for haemostasis. Then haemostasis efficacy,the hemorrhage rate after nasal packing removed and host response, such as nasal pain and headache, which evaluated pain degrees against NRS, were all observed. There was no significant difference between the two groups of the haemostatic effect. But the hemorrhage rate of treatment group was obviously lower than that of the control group after paching,in addition, host responses, such as nasal pain and headache, remarkably better than the control group, the difference had statistical significance. It is indicate that absorbable shanching satin rb-bFGF prepreg sheet presents reliable hemostasis effect, good biocompatibility and compliance; the pain and headache caused by packing are superior to vaseline gauze. Moreover, this method avoids the direct touch of vaseline gauze with nasal mucosal wound, and reduce hemorrhage after packing. Absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together is better to select the nasal packing material for blood disease patient with epistaxis.

Percutaneous suprapubic stone extraction for posterior urethral stones in children: efficacy and safety.

PubMed

Safwat, Ahmed S; Hameed, Diaa A; Elgammal, Mohamed A; Abdelsalam, Yasser M; Abolyosr, Ahmad

2013-08-01

To evaluate the safety and efficacy of percutaneous suprapubic stone extraction (PSPSE) for pediatric posterior urethral stones. Between July 2007 and June 2010, 54 boys presenting with acute urinary retention due to posterior urethral stones underwent PSPSE. Patients were a mean age of 66.4 months (range, 8-180 months). The stone size was 0.7-1.9 cm. Patients were placed under general anesthesia, and a 7F urethroscope was used to pushback the stone to the bladder. A 3-mm suprapubic puncture with a scalpel was performed, followed by insertion of a straight narrow hemostat through the puncture aided with cystoscopic guidance. The stone was grasped with the hemostat in its narrowest diameter and was extracted percutaneously or crushed if friable. The suprapubic puncture was closed with a single 4-0 Vicryl (Ethicon) suture. Intact stone retrieval was achieved in 45 patients, and the stone was crushed into minute fragments in 9 patients. Intraperitoneal extravasation developed in 1 patient that required open surgical intervention. Mean operative time was 22 minutes. Patients were monitored for up to 17 months, with complete resolution of symptoms and stone clearance. PSPSE provides a minimally invasive approach for the extraction of urethral and bladder stones in the pediatric population. The use of a straight hemostat for suprapubic stone extraction or crushing is a good alternative to suprapubic tract dilation, with minimal morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

Two speed factors of visual recognition independently correlated with fluid intelligence.

PubMed

Tachibana, Ryosuke; Namba, Yuri; Noguchi, Yasuki

2014-01-01

Growing evidence indicates a moderate but significant relationship between processing speed in visuo-cognitive tasks and general intelligence. On the other hand, findings from neuroscience proposed that the primate visual system consists of two major pathways, the ventral pathway for objects recognition and the dorsal pathway for spatial processing and attentive analysis. Previous studies seeking for visuo-cognitive factors of human intelligence indicated a significant correlation between fluid intelligence and the inspection time (IT), an index for a speed of object recognition performed in the ventral pathway. We thus presently examined a possibility that neural processing speed in the dorsal pathway also represented a factor of intelligence. Specifically, we used the mental rotation (MR) task, a popular psychometric measure for mental speed of spatial processing in the dorsal pathway. We found that the speed of MR was significantly correlated with intelligence scores, while it had no correlation with one's IT (recognition speed of visual objects). Our results support the new possibility that intelligence could be explained by two types of mental speed, one related to object recognition (IT) and another for manipulation of mental images (MR).

SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

PubMed Central

Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

2016-01-01

Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

Comparative Testing of Hemostatic Dressing in a Large Animal Model (Sus Scorofa) with Severe hepatic Injuries

DTIC Science & Technology

2013-12-02

applicable terms in EACH column) ___ Training: Live Animal ___ Medical Readiness ___ Prolonged Restraint ___ Training: non-Live Animal ... Health Promotion ___ Multiple Survival Surgery ___ Research: Survival (chronic) ___ Prevention ___ Behavioral Study _X__ Research

Clinical experience with fibrin glue in cardiac surgery.

PubMed

Köveker, G; de Vivie, E R; Hellberg, K D

1981-10-01

Cardiac surgery is often associated with hemostatic abnormalities leading to severe bleeding. Special problems are to be expected, if prosthetic material has to be implanted. Preclotting of Dacron prostheses with blood is well established but failures are sometimes encountered. Several years ago a new hemostatic sealing system (fibrin glue) was introduced into therapy. Since 1978 fibrin glue has been applied in 176 patients. The indications were: 1. sealing of woven Dacron prostheses, 2. bleeding from suture-holes (Gore-Tex), 3. diffuse myocardial bleeding and 4. prevention of kinking of coronary artery grafts. In 32 patients with an aortoventriculoplasty operation using Dacron the "blood preclotting" and "fibrin sealing" methods were compared. In the fibrin glue group there was a significant reduction in postoperative blood loss as well as a shortening of the operation time (period of protamin administration to skin closure). No fibrinolytic dissolution of the fibrin layer on the prostheses was observed.

Laser evaporation of the prostate: preliminary findings in canines

NASA Astrophysics Data System (ADS)

Kuntzman, R. S.; Malek, Reza S.; Barrett, David M.; Bostwick, David G.

1996-05-01

Purpose: We evaluated the ability of KTP laser to evaporate prostatic tissue in vivo and compared the results with historical Nd:YAG treated controls. Methods: Five dogs underwent anterograde transurethral evaporation of the prostate (TUEP) with KTP laser at 38 watts and were sacrificed 48 hours after surgery. Results: All procedures were hemostatic and without complications. Laser evaporation produced cavities within the prostate ranging from 2.5 to 3.2 cm in diameter (average equals 2.9 cm) that were free of necrotic tissue. Conclusions: Preliminary findings in this initial canine study of laser evaporation of the prostate, show that KTP laser produces large spherical cavities within the prostate in a hemostatic fashion. These cavities are free of necrotic tissue. In addition, these cavities are comparable in size to those that have been observed 4 to 8 weeks following Nd:YAG VLAP and are significantly larger than the acute cavities produced by Nd:YAG TUEP.

Hemostatic potential of natural/synthetic polymer based hydrogels crosslinked by gamma radiation

NASA Astrophysics Data System (ADS)

Barba, Bin Jeremiah D.; Tranquilan-Aranilla, Charito; Abad, Lucille V.

2016-01-01

Various raw materials and hydrogels prepared from their combination were assessed for hemostatic capability using swine whole blood clotting analysis. Initial screening showed efficient coagulative properties from κ-carrageenan and its carboxymethylated form, and α-chitosan, even compared to commercial products like QuikClot Zeolite Powder. Blending natural and synthetic polymers formed into hydrogels using gamma radiation produced materials with improved properties. KC and CMKC hydrogels were found to have the lowest blood clotting index in granulated form and had the higher capacity for platelet adhesion in foamed form compared to GelFoam. Possible mechanisms involved in the evident thrombogenicity of the materials include adsorption of platelets and related proteins that aid in platelet activation (primary hemostasis), absorption of water to concentrate protein factors that control the coagulation cascade, contact activation by its negatively charged surface and the formation of gel-blood clots.

The use of platelet-rich fibrin as a hemostatic material in oral soft tissues.

PubMed

de Almeida Barros Mourão, Carlos Fernando; Calasans-Maia, Mônica Diuana; de Mello Machado, Rafael Coutinho; de Brito Resende, Rodrigo Figueiredo; Alves, Gutemberg Gomes

2018-06-26

The control of postoperative bleeding represents one of the main intercurrent events associated with soft tissue surgical procedures in the oral cavity. In this context, platelet-rich fibrin (PRF) membranes are materials with great potential for optimizing soft tissue healing and induction of hemostasis. This interventional case series describes the treatment of 10 patients with excisional biopsy of benign oral cavity lesions, following a screening sequence at the surgery clinic of a Brazilian dental school between the years of 2015 and 2017. After treatment with PRF, patients presented mean time for postoperative hemostasis of 10.3 ± 2.5 s, requiring the average use of three membranes to cover the surgical area. The results suggest that the use of platelet-rich fibrin membranes may represent a feasible alternative hemostatic material for the treatment of oral lesions.

Myelofibrosis and acquired hemophilia A: a case report.

PubMed

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

Influence of stearic acid on postprandial lipemia and hemostatic function.

PubMed

Sanders, Thomas A B; Berry, Sarah E E

2005-12-01

It has been suggested that fats rich in stearic acid may result in exaggerated postprandial lipemia and have adverse effects on hemostatic function. The effects of test meals containing different saturated and monounsaturated FA were compared in healthy subjects in a series of studies to investigate this hypothesis. Stearic acid, when present as cocoa butter, resulted in similar postprandial lipemia and factor VII activation compared with a meal containing high-oleic sunflower oil. Stearic acid when presented as shea butter or as randomized stearate-rich TAG resulted in decreased postprandial lipemia and decreased postprandial activation of factor VII. Stearic acid-rich test meals did not result in impaired fibrinolytic activity compared with either a low-fat meal or a meal high in oleate. The difference in responses between the different stearic acid-rich fats appears to be due to varying solid fat contents of the fats at 37 degrees C.

Cardiovascular and Hemostatic Disorders: Role of STIM and Orai Proteins in Vascular Disorders.

PubMed

Tanwar, Jyoti; Trebak, Mohamed; Motiani, Rajender K

2017-01-01

Store-operated Ca 2+ entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca 2+ storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca 2+ levels and transmits the message to plasma membrane Ca 2+ channels constituted by Orai family members (Orai1/2/3) resulting in Ca 2+ influx into the cells. This increase in cytosolic Ca 2+ in turn activates a variety of signaling cascades to regulate a plethora of cellular functions. Evidence from the literature suggests that SOCE dysregulation is associated with several pathophysiologies, including vascular disorders. Interestingly, recent studies have suggested that STIM proteins may also regulate vascular functions independent of their contribution to SOCE. In this updated book chapter, we will focus on the physiological role of STIM and Orai proteins in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in vascular disease.

Threshold of microvascular occlusion: injury size defines the thrombosis scenario.

PubMed

Belyaev, Aleksey V; Panteleev, Mikhail A; Ataullakhanov, Fazly I

2015-07-21

Damage to the blood vessel triggers formation of a hemostatic plug, which is meant to prevent bleeding, yet the same phenomenon may result in a total blockade of a blood vessel by a thrombus, causing severe medical conditions. Here, we show that the physical interplay between platelet adhesion and hemodynamics in a microchannel manifests in a critical threshold behavior of a growing thrombus. Depending on the size of injury, two distinct dynamic pathways of thrombosis were found: the formation of a nonocclusive plug, if injury length does not exceed the critical value, and the total occlusion of the vessel by the thrombus otherwise. We develop a mathematical model that demonstrates that switching between these regimes occurs as a result of a saddle-node bifurcation. Our study reveals the mechanism of self-regulation of thrombosis in blood microvessels and explains experimentally observed distinctions between thrombi of different physical etiology. This also can be useful for the design of platelet-aggregation-inspired engineering solutions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Microchemical evidence for episodic growth of antitaxial veins during fracture-controlled fluid flow

NASA Astrophysics Data System (ADS)

Barker, Shaun L. L.; Cox, Stephen F.; Eggins, Stephen M.; Gagan, Michael K.

2006-10-01

The mechanism by which syntectonic hydrothermal veins form is widely debated, with some workers suggesting that certain vein textures are related to specific fluid flow regimes. Central to the debate is whether vein formation involves advective fluid flow, or occurs by local diffusion of material from the surrounding wall rock. To address this issue, we integrated textural observations and microchemical analyses of a hydrothermal vein from the Lachlan Orogen, southeast Australia, to reveal information about vein growth history, changes in fluid chemistry, and the evolution of fluid flow pathways during vein growth. The study area is part of a regional-scale fault-fracture network in an interbedded limestone-shale sequence, which formed at depths of ˜ 5-10 km (˜ 150-200 °C) during late Devonian crustal shortening. This integrated approach demonstrates that the zonation of textures, Sr isotopes, stable isotopes (C, O), and trace and rare earth elements is distinctly asymmetrical about the median growth-line of the vein. δ 18O values in vein calcite (17.0-18.8‰, VSMOW) are lower than those in surrounding unaltered limestones (23-25‰, VSMOW), and vary systematically across the vein. In contrast, δ 13C values are relatively constant across most of the vein, but become markedly depleted ( ca. 4‰) immediately adjacent to the wall rock. This strong depletion in δ 13C was probably caused by the influx of more oxidised fluids during the latest stages of vein growth. Strontium isotope ratios ( 87Sr/ 86Sr) vary between 0.70912 and 0.70931 across the vein. Abrubt changes in 87Sr/ 86Sr, δ 18O, Ce/Ce *, Eu/Eu * and trace element concentrations indicate that vein growth was accompanied by stepwise changes in the fluid flow pathway and consequent variations in fluid chemistry. Taken together, our findings are not consistent with growth of fibrous antitaxial veins by diffusional transfer of material from the surrounding wall rock. Instead, they suggest that externally sourced fluids migrated along episodically changing fracture-controlled flow pathways. This has implications for the dynamics of crustal permeability and mineralisation.

Computational reconstruction and fluid dynamics of in vivo thrombi from the microcirculation

NASA Astrophysics Data System (ADS)

Mirramezani, Mehran; Tomaiuolo, Maurizio; Stalker, Timothy; Shadden, Shawn

2016-11-01

Blood flow and mass transfer can have significant effects on clot growth, composition and stability during the hemostatic response. We integrate in vivo data with CFD to better understand transport processes during clot formation. By utilizing electron microscopy, we reconstructed the 3D thrombus structure formed after a penetrating laser injury in a mouse cremaster muscle. Random jammed packing is used to reconstruct the microenvironment of the platelet aggregate, with platelets modeled as ellipsoids. In our 3D model, Stokes flow is simulated to obtain the velocity field in the explicitly meshed gaps between platelets and the lumen surrounding the thrombus. Based on in vivo data, a clot is composed of a core of highly activated platelets covered by a shell of loosely adherent platelets. We studied the effects of clot size (thrombus growth), gap distribution (consolidation), and vessel blood flow rate on mean intrathrombus velocity. The results show that velocity is smaller in the core as compared to the shell, potentially enabling higher concentration of agonists in the core contributing to its activation. In addition, our results do not appear to be sensitive to the geometry of the platelets, but rather gap size plays more important role on intrathrombus velocity and transport.

Vascular, glial, and lymphatic immune gateways of the central nervous system.

PubMed

Engelhardt, Britta; Carare, Roxana O; Bechmann, Ingo; Flügel, Alexander; Laman, Jon D; Weller, Roy O

2016-09-01

Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

Massive transfusion and nonsurgical hemostatic agents.

PubMed

Perkins, Jeremy G; Cap, Andrew P; Weiss, Brendan M; Reid, Thomas J; Bolan, Charles D; Bolan, Charles E

2008-07-01

Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality. Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality. This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.

Effects of contamination by either blood or a hemostatic agent on the shear bond strength of orthodontic buttons

PubMed Central

Alkis, Huseyin; Turkkahraman, Hakan

2013-01-01

Objective To evaluate the effects of contamination by either blood or a hemostatic agent on the shear bond strength (SBS) of orthodontic buttons. Methods We used 45 freshly extracted, non-carious, impacted third molars that were divided into 3 groups of 15. Each tooth was etched with 37% phosphoric acid gel for 30 s. Human blood or the blood stopper agent was applied to the tooth surface in groups I and II, respectively. Group III teeth were untreated (controls). Orthodontic buttons were bonded to the teeth using light-curing composite resin. After bonding, the SBS of the button was determined using a Universal testing machine. Any adhesive remaining after debonding was assessed and scored according to the modified adhesive remnant index (ARI). ANOVA with post-hoc Tukey's test was used to determine significant differences in SBS and Fisher's exact test, to determine significant differences in ARI scores among groups. Results ANOVA indicated a significant difference between groups (p < 0.001). The highest SBS values were measured in group III (10.73 ± 0.96 MPa). The SBS values for teeth in groups I and II were significantly lower than that of group III (p < 0.001). The lowest SBS values were observed in group I teeth (4.17 ± 1.11 MPa) (p < 0.001). Conclusions Contamination of tooth surfaces with either blood or hemostatic agent significantly decreased the SBS of orthodontic buttons. When the contamination risk is high, it is recommended to use the blood stopper agent when bonding orthodontic buttons on impacted teeth. PMID:23671834

Pharmacologic Hemostatic Agents in Total Joint Arthroplasty-A Cost-Effectiveness Analysis.

PubMed

Ramkumar, Dipak B; Ramkumar, Niveditta; Tapp, Stephanie J; Moschetti, Wayne E

2018-03-03

Total knee and hip arthroplasties can be associated with substantial blood loss, affecting morbidity and even mortality. Two pharmacological antifibrinolytics, ε-aminocaproic acid (EACA) and tranexamic acid (TXA) have been used to minimize perioperative blood loss, but both have associated morbidity. Given the added cost of these medications and the risks associated with then, a cost-effectiveness analysis was undertaken to ascertain the best strategy. A cost-effectiveness model was constructed using the payoffs of cost (in United States dollars) and effectiveness (quality-adjusted life expectancy, in days). The medical literature was used to ascertain various complications, their probabilities, utility values, and direct medical costs associated with various health states. A time horizon of 10 years and a willingness to pay threshold of $100,000 was used. The total cost and effectiveness (quality-adjusted life expectancy, in days) was $459.77, $951.22, and $1174.87 and 3411.19, 3248.02, and 3342.69 for TXA, no pharmacologic hemostatic agent, and EACA, respectively. Because TXA is less expensive and more effective than the competing alternatives, it was the favored strategy. One-way sensitivity analyses for probability of transfusion and myocardial infarction for all 3 strategies revealed that TXA remains the dominant strategy across all clinically plausible values. TXA, when compared with no pharmacologic hemostatic agent and with EACA, is the most cost-effective strategy to minimize intraoperative blood loss in hip and knee total joint arthroplasties. These findings are robust to sensitivity analyses using clinically plausible probabilities. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-term results of laparoscopic treatment of esophageal achalasia in children: a multicentric survey.

PubMed

Esposito, Ciro; Riccipetitoni, Giovanna; Chiarenza, Salvatore Fabio; Roberti, Agnese; Vella, Claudio; Alicchio, Francesca; Fava, Giorgio; Escolino, Maria; De Pascale, Teresa; Settimi, Alessandro

2013-11-01

This report describes three Italian centers' experience in the treatment of children with esophageal achalasia. Between June 2000 and June 2012, 31 children (13 girls and 18 boys, with a median age of 8.4 years) affected by esophageal achalasia were treated in three different institutions with an esophagomyotomy according to Heller's procedure via laparoscopy associated with a Dor antireflux procedure. Between 2000 and 2005 (for 14 patients) we used mono- or bipolar coagulation to perform myotomy; after 2005 (for 17 patients) we used the new hemostatic devices to perform it. Median length of surgery was 120 minutes. Median hospital stay was 4 days. We recorded eight complications in our series: 3 patients (9.6%) had a mucosal perforation, and 5 children (16.1%) presented dysphagia after surgery. When comparing the data before and after 2005, it seems that the new hemostatic devices statistically shortened the length of surgery (P<.01, Student's t test). On the basis of our experience, laparoscopic Heller's myotomy associated with an antireflux procedure is a safe and effective method for the treatment of achalasia in the pediatric population. Intraoperative complications were <10%, and they occurred mostly at the beginning of our experience. Residual dysphagia occurred in about 16% of cases. The use of the new hemostatic devices seems to reduce the length of surgery and intraoperative bleeding. Considering the rarity of this pathology, we believe that patients with achalasia have to be treated only at centers with a strong experience in the treatment of this pathology.

Comparison of clinical and laboratory parameters in patients with end-stage renal failure in the outcome of chronic glomerulonephritis and patients with end-stage renal failure in the outcome of other diseases.

PubMed

Popova, J A; Yadrihinskaya, V N; Krylova, M I; Sleptsovа, S S; Borisovа, N V

frequent complications of hemodialysis treatments are coagulation disorders. This is due to activation of the coagulation of blood flow in the interaction with a dialysis membrane material vascular prostheses and extracorporeal circuit trunks. In addition, in hemodialysis patients receiving heparin for years, there is depletion of stocks in endothelial cells in tissue factor inhibitor, inhibits the activity of an external blood clotting mechanism. the aim of our study was to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure. to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure and hemodialysis treatment duration conducted a study that included 100 patients observed in the department of chronic hemodialysis and nephrology hospital №1 Republican National Medical Center in the period of 2013-2016. in patients with end-stage renal failure in the outcome of chronic glomerulonephritis, a great expression of activation of blood coagulation confirm increased the mean concentration of fibrinogen, whereas in the group, which included patients with end-stage renal failure in the outcome of other diseases, such is not different from the norm, and a higher rate of hyperfibrinogenemia, identified in 2/3 patients in this group. it was revealed that the state of homeostasis in patients with end-stage renal failure in increasingly characterizes the level of fibrinogen and the activation of the hemostatic markers: soluble fibrin monomer complexes, D-dimers.

[Comparison on Endoscopic Hemoclip and Hemoclip Combination Therapy in Non-variceal Upper Gastrointestinal Bleeding Patients Based on Clinical Practice Data: Is There Difference between Prospective Cohort Study and Randomized Study?].

PubMed

Lee, Su Hyun; Jung, Jin Tae; Lee, Dong Wook; Ha, Chang Yoon; Park, Kyung Sik; Lee, Si Hyung; Yang, Chang Heon; Park, Youn Sun; Jeon, Seong Woo

2015-08-01

Endoscopic hemoclip application is an effective and safe method of endoscopic hemostasis. We conducted a multicenter retrospective study on hemoclip and hemoclip combination therapy based on prospective cohort database in terms of hemostatic efficacy not in clinical trial but in real clinical practice. Data on endoscopic hemostasis for non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively collected from February 2011 to December 2013. Among 1,584 patients with NVUGIB, 186 patients treated with hemoclip were enrolled in this study. Subjects were divided into three groups: Group 1 (n = 62), hemoclipping only; group 2 (n = 88), hemoclipping plus epinephrine injection; and group 3 (n = 36), hemocliping and epinephrine injection plus other endoscopic hemostatic modalities. Primary outcomes included rebleeding, other therapeutic management, hospitalization period, fasting period and mortality. Secondary outcomes were bleeding associated mortality and overall mortality. Active bleeding and peptic ulcer bleeding were more common in group 3 than in group 1 and in group 2 (p <œ 0.001). However, primary outcomes (rebleeding, other management, morbidity, hospitalization period, fasting period and mortality) and secondary outcomes (bleeding associated mortality and total mortality) were not different among groups. Combination therapy of epinephrine injection and other modalities with hemoclips did not show advantage over hemoclipping alone in this prospective cohort study. However, there is a tendency to perform combination therapy in active bleeding which resulted in equivalent hemostatic success rate, and this reflects the role of combination therapy in clinical practice.

Coagulation monitoring during extracorporeal membrane oxygenation: the role of thrombelastography.

PubMed

Stammers, A H; Willett, L; Fristoe, L; Merrill, J; Stover, T; Hunt, A; Morrow, J; Newberry, J

1995-09-01

Patients undergoing extracorporeal membrane oxygenation (ECMO) are at an increased risk for developing coagulopathies due to the adverse effects of extracorporeal circulation on the hemostatic mechanism. Methods of determining causative factors of bleeding diathesis are often inconsistent and non-specific. ECMO patients require aggressive transfusion therapy with autogenic blood products to stabilize and maintain hemostasis. The present study evaluated the coagulation status of newborn patients undergoing ECMO therapy, using a viscoelastic monitor (Thrombelastograph -TEG) that measures functional aspects of clot development and stabilization. Seventeen neonatal patients undergoing ECMO for severe respiratory dysfunction were entered into this study. Serial blood samples were obtained and routine coagulation assessment including fibrinogen concentration, platelet count and ionized calcium was performed. In addition, fibrin(ogen) degradation products (FDP), d-Dimers, antithrombin III and plasma free hemoglobin were measured. Transfusion indicators were established and total transfusion requirements recorded. TEG profiles were determined with the use of heparinase, an enzyme that degrades heparin but has little effect on other coagulation factors. The most commonly encountered complication was hemorrhaging which was diagnosed by laboratory and clinical assessment in 11 of 17 patients. Transfusion requirements (measured in ml/kg/ECMO hour) were the following: packed red blood cells--1.34 +/- 0.5; platelets--0.71 +/- 0.57; fresh frozen plasma--0.09 +/- 0.12; cryoprecipitate 0.05 +/- 0.05. Thrombelastograph profiles reflected hemostatic conditions that ranged from severe coagulopathies (DIC) to hypercoagulability. Interpretation of TEG profiles identified hemostatic abnormalities in 57 of 101 profiles (46.5%), with the most common etiology related to platelet dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of hemostatic agents in preventing complications in laparoscopic partial nephrectomy

PubMed Central

y Gregorio, Sergio Alonso; Rivas, Juan Gómez; Bazán, Alfredo Aguilera; Sebastián, Jesús Díez; Martínez-Piñeiro, Luis

2017-01-01

Introduction Nephron-sparing surgery is currently the treatment of choice for renal cell carcinoma stage T1a. During the past years, several hemostatic agents (HA) have been developed in order to reduce surgical complications. We present the results of our series and the impact of the use of HA in the prevention of surgical complications in laparoscopic partial nephrectomies (LPNs). Material and methods We retrospectively analyzed all LPN performed in our center from 2005 to 2012. A total of 77 patients were included for analysis. Patients were divided into two groups: Group A (no use of HA) and Group B (use of HA). HA used included gelatin matrix thrombin (FloSeal) and oxidized regenerated cellulose (Surgicel). Demographics, perioperative variables, and complications were analyzed with a special interest in postoperative bleeding and urinary leakage. Results Median age was 57.17 years old (±12.1), 72.7% were male, most common comorbidities were hypertension (33.8%) and diabetes mellitus (18.2%). All patients had one solitary tumor, and 87% had a tumor ≤4 cm. Renal cell carcinoma was found in 79.2% of cases, and 78.7% were stage pT1a. and were used in 36 cases (46.8%). No differences were found in demographics, perioperative variables, and complications between groups. No conversions to open surgery or perioperative mortality were reported. Conclusions We conclude that in our series the use of a hemostatic agent did not offer benefit in reducing the complication rate over sutures over a bolster. PMID:29410886

Characterizing the O-glycosylation landscape of human plasma, platelets, and endothelial cells

PubMed Central

King, Sarah L.; Joshi, Hiren J.; Schjoldager, Katrine T.; Halim, Adnan; Madsen, Thomas D.; Dziegiel, Morten H.; Woetmann, Anders; Vakhrushev, Sergey Y.

2017-01-01

The hemostatic system comprises platelet aggregation, coagulation, and fibrinolysis, and is critical to the maintenance of vascular integrity. Multiple studies indicate that glycans play important roles in the hemostatic system; however, most investigations have focused on N-glycans because of the complexity of O-glycan analysis. Here we performed the first systematic analysis of native-O-glycosylation using lectin affinity chromatography coupled to liquid chromatography mass spectrometry (LC-MS)/MS to determine the precise location of O-glycans in human plasma, platelets, and endothelial cells, which coordinately regulate hemostasis. We identified the hitherto largest O-glycoproteome from native tissue with a total of 649 glycoproteins and 1123 nonambiguous O-glycosites, demonstrating that O-glycosylation is a ubiquitous modification of extracellular proteins. Investigation of the general properties of O-glycosylation established that it is a heterogeneous modification, frequently occurring at low density within disordered regions in a cell-dependent manner. Using an unbiased screen to identify associations between O-glycosites and protein annotations we found that O-glycans were over-represented close (± 15 amino acids) to tandem repeat regions, protease cleavage sites, within propeptides, and located on a select group of protein domains. The importance of O-glycosites in proximity to proteolytic cleavage sites was further supported by in vitro peptide assays demonstrating that proteolysis of key hemostatic proteins can be inhibited by the presence of O-glycans. Collectively, these data illustrate the global properties of native O-glycosylation and provide the requisite roadmap for future biomarker and structure-function studies. PMID:29296958

Mechanisms of Normal and Abnormal Endometrial Bleeding

PubMed Central

Lockwood, Charles J.

2011-01-01

Expression of tissue factor (TF), the primary initiator of coagulation, is enhanced in decidualized human endometrial stromal cells (HESC) during the progesterone-dominated luteal phase. Progesterone also augments a second HESC hemostatic factor, plasminogen activator inhibitor-1 (PAI-1). In contrast, progestins inhibit HESC matrix metalloproteinase (MMP)-1, 3 and 9 expression to stabilize endometrial stromal and vascular extracellular matrix. Through these mechanisms decidualized endometrium is rendered both hemostatic and resistant to excess trophoblast invasion in the mid-luteal phase and throughout gestation to prevent hemorrhage and accreta. In non-fertile cycles, progesterone withdrawal results in decreased HESC TF and PAI-expression and increased MMP activity and inflammatory cytokine production promoting the controlled hemorrhage of menstruation and related tissue sloughing. In contrast to these well ordered biochemical processes, unpredictable endometrial bleeding associated with anovulation reflects absence of progestational effects on TF, PAI-1 and MMP activity as well as unrestrained angiogenesis rendering the endometrium non-hemostatic, proteolytic and highly vascular. Abnormal bleeding associated with long-term progestin-only contraceptives results not from impaired hemostasis but from unrestrained angiogenesis leading to large fragile endometrial vessels. This abnormal angiogenesis reflects progestational inhibition of endometrial blood flow promoting local hypoxia and generation of reactive oxygen species that increase production of angiogenic factors such as vascular endothelial growth factor (VEGF) in HESCs and Angiopoietin-2 (Ang-2) in endometrial endothelial cells while decreasing HESC expression of angiostatic, Ang-1. The resulting vessel fragility promotes bleeding. Aberrant angiogenesis also underlies abnormal bleeding associated with myomas and endometrial polyps however there are gaps in our understanding of this pathology. PMID:21499503

Microwave coagulation therapy and drug injection to treat splenic injury.

PubMed

Zhang, Guoming; Sun, Yuanyuan; Yu, Jie; Dong, Lei; Mu, Nannan; Liu, Xiaohong; Liu, Lanfen; Zhang, Yan; Wang, Xiaofei; Liang, Ping

2014-01-01

The present study compares the efficacy of 915- and 2450-MHz contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave coagulation with that of CEUS-guided thrombin injection for the treatment of trauma-induced spleen hemorrhage. In a canine splenic artery hemorrhage model with two levels of arterial diameter (A, <1 mm and B, between 1 and 2 mm), hemostatic therapy was performed using 915- and 2450-MHz microwaves and drug injection. Therapy efficacy was measured by comparing bleeding rate, hemostatic time, bleeding index, bleeding volume, and pathology. The most efficient technique was CEUS-guided 915-MHz percutaneous microwave coagulation therapy in terms of action time and total blood loss. The success rate of the 915-MHz microwave group was higher than that of the 2450-MHz microwave and the drug injection groups (except A level, P < 0.05). Hemostatic time, bleeding index, and bleeding volume were significantly less in the 915-MHz microwave group than those in the 2450-MHz microwave and drug injection groups (P < 0.05). Obvious degeneration and necrosis of parenchyma and large intravascular thrombosis were observed in the cavity of larger vessels in the 915-MHz microwave group, but pathologic changes of light injury could be seen in the other groups. The present study provides evidence that microwave coagulation therapy is more efficient than thrombin injection for the treatment of splenic hemorrhage. Furthermore, treatment with 915-MHz microwaves stops bleeding more rapidly and generates a wider cauterization zone than does treatment with 2450-MHz microwaves. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative Study of the Effects of Combined Oral Contraceptives in Hemostatic Variables

PubMed Central

Stocco, Bianca; Fumagalli, Helen F.; Franceschini, Silvio A.; Martinez, Edson Z.; Marzocchi-Machado, Cleni M.; de Sá, Marcos Felipe S.; Toloi, Maria Regina T.

2015-01-01

Abstract Thrombotic risk is associated with the estrogen dose and type of progestin in combined oral contraceptives. Studies published since 1990 showed that third-generation progestins have larger risk to contribute to thrombosis development than the second-generation. However, there are conflicts in the literature regarding the thrombotic risk associated to the drospirenone progestin. So, this study aimed to evaluate the effects of 3 formulations of contraceptives containing ethinylestradiol (EE) (20 and 30 μg) combined with drospirenone versus levonorgestrel combined with EE (30 μg) in hemostatic parameters. This cross-sectional study included 70 healthy women between 18 and 30 years, BMI 19 to 30 kg/m2, not pregnant, non-smokers, and users or non-users (control) of contraceptives for a minimum period of 6 months. The following parameters were assessed: prothrombin time (PT), Factor VII, activated partial thromboplastin time (aPTT), Factor XII, fibrinogen, Factor 1 + 2, Protein C, Protein S, antithrombin, D-dimers, and plasminogen activator inhibitor-1. Significant alterations were found in PT, aPTT, fibrinogen, D-dimers, and protein S, all favoring a state of hypercoagulation for contraceptive containing DRSP/20EE. Both contraceptives containing DRSP/30EE and LNG/30EE promoted changes that favor the hypercoagulability in the coagulant variable PT and in the anticoagulant variables Protein S and Protein C, respectively. We suggest that the progestin drospirenone can contribute to an inadequate balance among procoagulant, anticoagulant, and fibrinolytic factors, since that the contraceptive containing the lowest dose of estrogen and drospirenone (DRSP/20EE) caused a higher number of hemostatic changes. PMID:25634167

Real-world surgical outcomes of a gelatin-hemostatic matrix in women requiring a hysterectomy: a matched case-control study.

PubMed

Obermair, Helena; Janda, Monika; Obermair, Andreas

2016-09-01

The aim of this study was to compare adverse events and surgical outcomes of hysterectomy with or without use of a gelatin-hemostatic matrix (SURGIFLO(®) ). Prospective case-control study (Canadian Task Force classification II2) of total hysterectomy (Piver Type 1) provided by surgeons in Australia between November 2005 and May 2015. Data were collected via SurgicalPerformance, a web-based data project which aims to provide confidential feedback to surgeons about their surgical outcomes. Of 2440 records of women who received a hysterectomy, 1351 were eligible for these analyses; 107 received SURGIFLO(®) hemostatic matrix to prevent postoperative blood loss and 1244 did not. Patients with or without SURGIFLO(®) differed in age, Charlson comorbidity index, and American Society of Anesthesiologists physical status classification system score (ASA), and also differed in clinical outcomes. After matching for patient's age and ASA at surgery, patients with and without SURGIFLO(®) had comparable baseline characteristics. Matched patients with and without SURGIFLO(®) had comparable clinical outcomes including risk of developing vault hematoma, return to the operating room, transfusion of red cells, surgical site infection (pelvis), readmission within 30 days and unplanned ICU admission. In a sample matched by age and ASA, SURGIFLO(®) neither prevented nor caused additional adverse events in women undergoing hysterectomy. Surgeons used SURGIFLO(®) more commonly among women who were older, had more comorbidities and a higher ASA score. This indicates that it may be most useful in complicated surgery or cases. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

PubMed

Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

2017-04-01

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients < 12 years of age with severe hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to < 6 years, n = 35; ≥ 6 to < 12 years, n = 49); 81 were assigned to prophylaxis and three to an on-demand regimen. Patients accumulated a total of 5239 exposure days (EDs), with 65 participants reaching > 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children < 12 years of age with severe hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Activated complement components and complement activator molecules on the surface of cell‐derived microparticles in patients with rheumatoid arthritis and healthy individuals

PubMed Central

Biró, Éva; Nieuwland, Rienk; Tak, Paul P; Pronk, Loes M; Schaap, Marianne C L; Sturk, Augueste; Hack, C Erik

2007-01-01

Objectives In vitro, microparticles can activate complement via the classical pathway. If demonstrable ex vivo, this mechanism may contribute to the pathogenesis of rheumatoid arthritis (RA). We therefore investigated the presence of activated complement components and complement activator molecules on the surface of cell‐derived microparticles of RA patients and healthy individuals. Methods Microparticles from synovial fluid (n = 8) and plasma (n = 9) of 10 RA patients and plasma of sex‐ and age‐matched healthy individuals (n = 10) were analysed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C‐reactive protein (CRP), serum amyloid P component (SAP), immunoglobulin (Ig) M, IgG). Results Microparticles with bound C1q, C4, and/or C3 were abundant in RA synovial fluid, while in RA and control plasma much lower levels were present. Microparticles with bound C1q correlated with those with bound C3 in synovial fluid (r = 0.961, p = 0.0001), and with those with bound C4 in plasma (RA: r = 0.908, p = 0.0007; control: r = 0.632, p = 0.0498), indicating classical pathway activation. In synovial fluid, microparticles with IgM and IgG correlated with those with C1q (r = 0.728, p = 0.0408; r = 0.952, p = 0.0003, respectively), and in plasma, microparticles with CRP correlated with those with C1q (RA: r = 0.903, p = 0.0021; control: r = 0.683, p = 0.0296), implicating IgG and IgM in the classical pathway activation in RA synovial fluid, and CRP in the low level classical pathway activation in plasma. Conclusions This study demonstrates the presence of bound complement components and activator molecules on microparticles ex vivo, and supports their role in low grade complement activation in plasma and increased complement activation in RA synovial fluid. PMID:17261534

Fluid inclusions in calcite filled opening fractures of the Serra Alta Formation reveal paleotemperatures and composition of diagenetic fluids percolating Permian shales of the Paraná Basin

NASA Astrophysics Data System (ADS)

Teixeira, C. A. S.; Sawakuchi, A. O.; Bello, R. M. S.; Nomura, S. F.; Bertassoli, D. J.; Chamani, M. A. C.

2018-07-01

The thermal and diagenetic evolution of shale units has received renewed focus because of their emergence as unconventional hydrocarbon reservoirs. The Serra Alta Formation (SAF) is a Permian shale unit of the Paraná Basin, which is the largest South American cratonic basin. The SAF stands out as a pathway for aqueous fluids and hydrocarbon migration from the Irati organic-rich shales to the Pirambóia fluvial-eolian sandstone reservoirs. Vertical NNW and NNE opening fractures would be the main pathways for the migration of buried pore waters and aqueous fluids, besides the input of meteoric water. These fractures would be associated to the reactivation of basement discontinuities such as the Jacutinga (NE) and Guapiara (NW) faults. Thus, vertical NNE and NNW associated fractures would represent the main pathways for fluid migration in the studied area. The vertical calcite filled opening fractures from SAF record moderately low salinity (0-4.5 wt % of NaCl eq.) aqueous fluids, suggesting the input of meteoric water in the buried fracture system. Eutectic melting temperatures at -52±5 °C indicate an H2O + NaCl + CaCl2 system with CaCl2 or MgCl2 in solution. Homogenization temperatures recorded in fluid inclusion assemblages (FIAs) of calcite filled opening fractures indicate that the SAF in the studied area reached temperatures above 200 °C, suitable for generation of gaseous hydrocarbons. The recorded paleotemperatures point to a thermal peak associated with Serra Geral volcanic event during the Early Cretaceous, with the thermal effect of volcanic rock cap possibly overcoming the effect of intrusive igneous bodies. The detection of methane in SAF shale pores indicates conditions for hydrocarbon generation. However, additionally studies are necessary to confirm the thermogenic and/or biogenic origin of the methane within the SAF.

Formation of magmatic brine lenses via focussed fluid-flow beneath volcanoes

NASA Astrophysics Data System (ADS)

Afanasyev, Andrey; Blundy, Jon; Melnik, Oleg; Sparks, Steve

2018-03-01

Many active or dormant volcanoes show regions of high electrical conductivity at depths of a few kilometres beneath the edifice. We explore the possibility that these regions represent lenses of high-salinity brine separated from a single-phase magmatic fluid containing H2O and NaCl. Since chloride-bearing fluids are highly conductive and have an exceptional capacity to transport metals, these regions can be an indication of an active hydrothermal ore-formation beneath volcanoes. To investigate this possibility we have performed hydrodynamic simulations of magma degassing into permeable rock. In our models the magma source is located at 7 km depth and the fluid salinity approximates that expected for fluids released from typical arc magmas. Our model differs from previous models of a similar process because it is (a) axisymmetric and (b) includes a static high-permeability pathway that links the magma source to the surface. This pathway simulates the presence of a volcanic conduit and/or plexus of feeder dykes that are typical of most volcanic systems. The presence of the conduit leads to a number of important hydrodynamic consequences, not observed in previous models. Importantly, we show that an annular brine lens capped by crystallised halite is likely to form above an actively degassing sub-volcanic magma body and can persist for more than 250 kyr after degassing ceases. Parametric analysis shows that brine lenses are more prevalent when the fluid is released at temperatures above the wet granite solidus, when magmatic fluid salinity is high, and when the high-permeability pathway is narrow. The calculated depth, form and electrical conductivity of our modelled system shares many features with published magnetotelluric images of volcano subsurfaces. The formation and persistence of sub-volcanic brine lenses has implications for geothermal systems and hydrothermal ore formation, although these features are not explored in the presented model.

Two Speed Factors of Visual Recognition Independently Correlated with Fluid Intelligence

PubMed Central

Tachibana, Ryosuke; Namba, Yuri; Noguchi, Yasuki

2014-01-01

Growing evidence indicates a moderate but significant relationship between processing speed in visuo-cognitive tasks and general intelligence. On the other hand, findings from neuroscience proposed that the primate visual system consists of two major pathways, the ventral pathway for objects recognition and the dorsal pathway for spatial processing and attentive analysis. Previous studies seeking for visuo-cognitive factors of human intelligence indicated a significant correlation between fluid intelligence and the inspection time (IT), an index for a speed of object recognition performed in the ventral pathway. We thus presently examined a possibility that neural processing speed in the dorsal pathway also represented a factor of intelligence. Specifically, we used the mental rotation (MR) task, a popular psychometric measure for mental speed of spatial processing in the dorsal pathway. We found that the speed of MR was significantly correlated with intelligence scores, while it had no correlation with one’s IT (recognition speed of visual objects). Our results support the new possibility that intelligence could be explained by two types of mental speed, one related to object recognition (IT) and another for manipulation of mental images (MR). PMID:24825574

Flow-induced protein kinase A–CREB pathway acts via BMP signaling to promote HSC emergence

PubMed Central

Kim, Peter Geon; Nakano, Haruko; Das, Partha P.; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Sakamoto, Kathleen M.; Zon, Leonard I.; Schlaeger, Thorsten M.; Orkin, Stuart H.; Nakano, Atsushi

2015-01-01

Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aorta–gonad–mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)–cAMP response element-binding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB. By chemical modulation of the PKA–CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA–CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP ligands through the type I BMP receptor. Finally, we observed blunting of this signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular flow. Collectively, we have identified a novel PKA–CREB–BMP signaling pathway downstream of shear stress that regulates HSC emergence in the AGM via the endothelial-to-hematopoietic transition. PMID:25870201

Evaluation of Yersinia pestis Transmission Pathways for Sylvatic Plague in Prairie Dog Populations in the Western U.S.

PubMed

Richgels, Katherine L D; Russell, Robin E; Bron, Gebbiena M; Rocke, Tonie E

2016-06-01

Sylvatic plague, caused by the bacterium Yersinia pestis, is periodically responsible for large die-offs in rodent populations that can spillover and cause human mortalities. In the western US, prairie dog populations experience nearly 100% mortality during plague outbreaks, suggesting that multiple transmission pathways combine to amplify plague dynamics. Several alternate pathways in addition to flea vectors have been proposed, such as transmission via direct contact with bodily fluids or inhalation of infectious droplets, consumption of carcasses, and environmental sources of plague bacteria, such as contaminated soil. However, evidence supporting the ability of these proposed alternate pathways to trigger large-scale epizootics remains elusive. Here we present a short review of potential plague transmission pathways and use an ordinary differential equation model to assess the contribution of each pathway to resulting plague dynamics in black-tailed prairie dogs (Cynomys ludovicianus) and their fleas (Oropsylla hirsuta). Using our model, we found little evidence to suggest that soil contamination was capable of producing plague epizootics in prairie dogs. However, in the absence of flea transmission, direct transmission, i.e., contact with bodily fluids or inhalation of infectious droplets, could produce enzootic dynamics, and transmission via contact with or consumption of carcasses could produce epizootics. This suggests that these pathways warrant further investigation.

Evaluation of Yersinia pestis transmission pathways for sylvatic plague in prairie dog populations in the western U.S.

USGS Publications Warehouse

Richgels, Katherine L. D.; Russell, Robin E.; Bron, Gebbiena; Rocke, Tonie E.

2016-01-01

Sylvatic plague, caused by the bacterium Yersinia pestis, is periodically responsible for large die-offs in rodent populations that can spillover and cause human mortalities. In the western US, prairie dog populations experience nearly 100% mortality during plague outbreaks, suggesting that multiple transmission pathways combine to amplify plague dynamics. Several alternate pathways in addition to flea vectors have been proposed, such as transmission via direct contact with bodily fluids or inhalation of infectious droplets, consumption of carcasses, and environmental sources of plague bacteria, such as contaminated soil. However, evidence supporting the ability of these proposed alternate pathways to trigger large-scale epizootics remains elusive. Here we present a short review of potential plague transmission pathways and use an ordinary differential equation model to assess the contribution of each pathway to resulting plague dynamics in black-tailed prairie dogs (Cynomys ludovicianus) and their fleas (Oropsylla hirsuta). Using our model, we found little evidence to suggest that soil contamination was capable of producing plague epizootics in prairie dogs. However, in the absence of flea transmission, direct transmission, i.e., contact with bodily fluids or inhalation of infectious droplets, could produce enzootic dynamics, and transmission via contact with or consumption of carcasses could produce epizootics. This suggests that these pathways warrant further investigation.

Could Fluid Seeps Originate from the Seismogenic Zone? Evidence from Southern Costa Rica

NASA Astrophysics Data System (ADS)

Silver, E. A.; Kluesner, J. W.; Nale, S. M.; Bangs, N. L.; McIntosh, K. D.; Ranero, C. R.; Tryon, M. D.; Spinelli, G. A.; Rathburn, T.; von Huene, R.

2013-12-01

The prevailing conceptual model of convergent margin hydrogeology is one in which fluid sourced from porosity loss and dehydration reactions seaward of the updip limit of the seismogenic zone reach the seafloor via relatively low angle splay faults that act as high permeability conduits through an otherwise nearly impermeable upper plate [e.g., Lauer and Saffer, GRL, 39:L13604, 2012; Saffer and Tobin, Ann. Rev. Earth Planet. Sci., 39:157-186, 2011]. Interpretation of newly acquired 3D seismic reflection data and high resolvability multibeam and backscatter data, showing evidence for abundant potential fluid seeps sourced beneath the sediment cover and farther landward than previously thought possible, may require reevaluation of this concept. Kluesner et al. [2013, G3, doi:10.1002/ggge.20058], identified 160 potential fluid seeps in an 11 km wide swath off southern Costa Rica, based on pockmarks and high backscatter mounds, each showing subsurface indicators of fluid migration in the seismic data. Approximately half of these potential seeps are on the outer continental shelf; these are landward of the updip limit of the seismogenic zone, as estimated by both the transition from high to low reflectivity of the plate boundary and the intersection of the 150°C isotherm with the plate boundary [Ranero et al., 2008, G3, doi:10.1029/2007GC001679; Bangs et al., 2012, AGU Fall Meeting, T13A-2587; Bangs et al., this meeting]. We have mapped high probability fluid pathways beneath these potential seeps, based on seismic meta-attribute volumes calculated using user-trained neural network algorithms [Kluesner et al., this meeting]. The mapped fluid pathways are high-angle through the sedimentary section, and they root into basement highs and basement faults. Fluids could originate along the plate interface, where potential sources and pathways are known (Mid-slope sites: Hensen et al., 2004, Geology, 32:201-204), or above or below the interface, although sources from these regions have not been reported. They could travel near vertical paths through the crustal rocks, or along a landward-dipping path, because the seismic data show landward dips but not seaward dips. If the fluids do come from the plate interface, they originate in the seismogenic zone. This inference can be tested by geochemical study of the outer shelf fluid seeps, where such sampling has not yet occurred.

Protein kinases as mediators of fluid shear stress stimulated signal transduction in endothelial cells: a hypothesis for calcium-dependent and calcium-independent events activated by flow.

PubMed

Berk, B C; Corson, M A; Peterson, T E; Tseng, H

1995-12-01

Fluid shear stress regulates endothelial cell function, but the signal transduction mechanisms involved in mechanotransduction remain unclear. Recent findings demonstrate that several intracellular kinases are activated by mechanical forces. In particular, members of the mitogen-activated protein (MAP) kinase family are stimulated by hyperosmolarity, stretch, and stress such as heat shock. We propose a model for mechanotransduction in endothelial cells involving calcium-dependent and calcium-independent protein kinase pathways. The calcium-dependent pathway involves activation of phospholipase C, hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), increases in intracellular calcium and stimulation of kinases such as calcium-calmodulin and C kinases (PKC). The calcium-independent pathway involves activation of a small GTP-binding protein and stimulation of calcium-independent PKC and MAP kinases. The calcium-dependent pathway mediates the rapid, transient response to fluid shear stress including activation of nitric oxide synthase (NOS) and ion transport. In contrast, the calcium-independent pathway mediates a slower response including the sustained activation of NOS and changes in cell morphology and gene expression. We propose that focal adhesion complexes link the calcium-dependent and calcium-independent pathways by regulating activity of phosphatidylinositol 4-phosphate (PIP) 5-kinase (which regulates PIP2 levels) and p125 focal adhesion kinase (FAK, which phosphorylates paxillin and interacts with cytoskeletal proteins). This model predicts that dynamic interactions between integrin molecules present in focal adhesion complexes and membrane events involved in mechanotransduction will be integrated by calcium-dependent and calcium-independent kinases to generate intracellular signals involved in the endothelial cell response to flow.

LC-MS/MS-based quantification of kynurenine metabolites, tryptophan, monoamines and neopterin in plasma, cerebrospinal fluid and brain.

PubMed

Fuertig, René; Ceci, Angelo; Camus, Sandrine M; Bezard, Erwan; Luippold, Andreas H; Hengerer, Bastian

2016-09-01

The kynurenine (KYN) pathway is implicated in diseases such as cancer, psychiatric, neurodegenerative and autoimmune disorders. Measurement of KYN metabolite levels will help elucidating the involvement of the KYN pathway in the disease pathology and inform drug development. Samples of plasma, cerebrospinal fluid or brain tissue were spiked with deuterated internal standards, processed and analyzed by LC-MS/MS; analytes were chromatographically separated by gradient elution on a C18 reversed phase analytical column without derivatization. We established an LC-MS/MS method to measure 11 molecules, namely tryptophan, KYN, 3-OH-KYN, 3-OH-anthranilic acid, quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, serotonin, dopamine and neopterin within 5.5 min, with sufficient sensitivity to quantify these molecules in small sample volumes of plasma, cerebrospinal fluid and brain tissue.

Drilling into a present-day migration pathway for hydrocarbons within a fault zone conduit in the Eugene Island 330 field, offshore Louisiana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, R.N.

1995-11-01

Within the Global Basins Research Network, we have developed 4-D seismic analysis techniques that, when integrated with pressure and temperature mapping, production history, geochemical monitoring, and finite element modeling, allow for the imaging of active fluid migration in the subsurface. We have imaged fluid flow pathways that are actively recharging shallower hydrocarbon reservoirs in the Eugene Island 330 field, offshore Louisiana. The hydrocarbons appear to be sourcing from turbidite stacks within the salt-withdrawal mini-basin buried deep within geopressure. Fault zone conduits provide transient migration pathways out of geopressure. To accomplish this 4-D imaging, we use multiple 3-D seismic surveys donemore » several years apart over the same blocks. 3-D volume processing and attribute analysis algorithms are used to identify significant seismic amplitude interconnectivity and changes over time that result from active fluid migration. Pressures and temperatures are then mapped and modeled to pro- vide rate and timing constraints for the fluid movement. Geochemical variability observed in the shallow reservoirs is attributed to the mixing of new with old oils. The Department of Energy has funded an industry cost-sharing project to drill into one of these active conduits in Eugene Island Block 330. Active fluid flow was encountered within the fault zone in the field demonstration experiment, and hydrocarbons were recovered. The active migration events connecting shallow reservoirs to deep sourcing regions imply that large, heretofore undiscovered hydrocarbon reserves exist deep within geopressures along the deep continental shelf of the northern Gulf of Mexico.« less

Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-15-1-0419 TITLE: Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease...COVERED 1 Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal...inappropriate cell growth, fluid secretion, and dysregulation of cellular energy metabolism. The enzyme AMPK regulates a number of cellular pathways, including

Sys-BodyFluid: a systematical database for human body fluid proteome research

PubMed Central

Li, Su-Jun; Peng, Mao; Li, Hong; Liu, Bo-Shu; Wang, Chuan; Wu, Jia-Rui; Li, Yi-Xue; Zeng, Rong

2009-01-01

Recently, body fluids have widely become an important target for proteomic research and proteomic study has produced more and more body fluid related protein data. A database is needed to collect and analyze these proteome data. Thus, we developed this web-based body fluid proteome database Sys-BodyFluid. It contains eleven kinds of body fluid proteomes, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, seminal fluid, human milk and amniotic fluid. Over 10 000 proteins are presented in the Sys-BodyFluid. Sys-BodyFluid provides the detailed protein annotations, including protein description, Gene Ontology, domain information, protein sequence and involved pathways. These proteome data can be retrieved by using protein name, protein accession number and sequence similarity. In addition, users can query between these different body fluids to get the different proteins identification information. Sys-BodyFluid database can facilitate the body fluid proteomics and disease proteomics research as a reference database. It is available at http://www.biosino.org/bodyfluid/. PMID:18978022

Sys-BodyFluid: a systematical database for human body fluid proteome research.

PubMed

Li, Su-Jun; Peng, Mao; Li, Hong; Liu, Bo-Shu; Wang, Chuan; Wu, Jia-Rui; Li, Yi-Xue; Zeng, Rong

2009-01-01

Recently, body fluids have widely become an important target for proteomic research and proteomic study has produced more and more body fluid related protein data. A database is needed to collect and analyze these proteome data. Thus, we developed this web-based body fluid proteome database Sys-BodyFluid. It contains eleven kinds of body fluid proteomes, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, seminal fluid, human milk and amniotic fluid. Over 10,000 proteins are presented in the Sys-BodyFluid. Sys-BodyFluid provides the detailed protein annotations, including protein description, Gene Ontology, domain information, protein sequence and involved pathways. These proteome data can be retrieved by using protein name, protein accession number and sequence similarity. In addition, users can query between these different body fluids to get the different proteins identification information. Sys-BodyFluid database can facilitate the body fluid proteomics and disease proteomics research as a reference database. It is available at http://www.biosino.org/bodyfluid/.

Fluid mechanics in the perivascular space.

PubMed

Wang, Peng; Olbricht, William L

2011-04-07

Perivascular space (PVS) within the brain is an important pathway for interstitial fluid (ISF) and solute transport. Fluid flowing in the PVS can affect these transport processes and has significant impacts on physiology. In this paper, we carry out a theoretical analysis to investigate the fluid mechanics in the PVS. With certain assumptions and approximations, we are able to find an analytical solution to the problem. We discuss the physical meanings of the solution and particularly examine the consequences of the induced fluid flow in the context of convection-enhanced delivery (CED). We conclude that peristaltic motions of the blood vessel walls can facilitate fluid and solute transport in the PVS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evidence For Different Reaction Pathways For Liquid And Granular Micronutrients In A Calcareous Soil

EPA Science Inventory

The benefits of Mn and Zn fluid fertilizers over conventional granular products in calcareous sandy loam soils have been agronomically demonstrated. We hypothesized that the differences in the effectiveness between granular and fluid Mn and Zn fertilizers is due to different Mn ...

Influences of growth parameters on the reaction pathway during GaN synthesis

NASA Astrophysics Data System (ADS)

Zhang, Zhi; Liu, Zhongyi; Fang, Haisheng

2018-01-01

Gallium nitride (GaN) film growth is a complicated physical and chemical process including fluid flow, heat transfer, species transport and chemical reaction. Study of the reaction mechanism, i.e., the reaction pathway, is important for optimizing the growth process in the actual manufacture. In the paper, the growth pathway of GaN in a closed-coupled showerhead metal-organic chemical vapor deposition (CCS-MOCVD) reactor is investigated in detail using computational fluid dynamics (CFD). Influences of the process parameters, such as the chamber pressure, the inlet temperature, the susceptor temperature and the pre-exponential factor, on the reaction pathway are examined. The results show that increases of the chamber pressure or the inlet temperature, as well as reductions of the susceptor temperature or the pre-exponential factor lead to the adduct route dominating the growth. The deposition rate contributed by the decomposition route, however, can be enhanced dramatically by increasing the inlet temperature, the susceptor temperature and the pre-exponential factor.

The role of grain boundaries and transient porosity increase as fluid pathways for reaction front propagation

NASA Astrophysics Data System (ADS)

Jonas, Laura; John, Timm; Geisler, Thorsten; Putnis, Andrew

2013-04-01

The pseudomorphic replacement of Carrara marble by calcium phosphates was studied as a model system to examine the influence of different fluid pathways for reaction front propagation induced by fluid-rock interaction. In this model system, the grain boundaries present in the rock and the transient porosity structures developing throughout the replacement reaction enable the reaction front to progress further into the rock as well as to the center of each single grain until complete transformation. Hydrothermal treatment of the marble using phosphate bearing solutions at temperature levels of 150° C and 200° C for different durations lead to the formation of two product phases which were identified as hydroxyapatite [Ca5(PO4)3OH] as well as β-tricalcium phosphate [β-Ca3(PO4)2] (β-TCP). The formation of β-TCP was probably favored by the presence of ~0.6wt.% of Mg in the parent phase. Completely transformed single grains show a distinctive zoning, both in composition and texture. Whereas areas next to the grain boundary consist of nearly pure hydroxyapatite and show a coarse porosity, areas close to the center of the single grains show a high amount of β-TCP and a very fine porous microstructure. If F was added as an additional solution component, the formation of β-TCP was avoided and up to 3wt.% of F were incorporated into the product apatite. The use of the isotope 18O as a chronometer for the replacement reaction makes it possible to reconstruct the chronological development of the calcium phosphate reaction front. Raman analysis revealed that the incorporation of 18O in the PO4 tetrahedron of hydroxyapatite results in the development of distinct profiles in the calcium phosphate reaction front perpendicular to the grain boundaries of the marble. Through the use of the 18O chronometer, it is possible to estimate and compare the time effectiveness of the different fluid pathways in this model system. The results show that the grain boundaries serve as a very effective pathway that enable the fluid to penetrate the rock more than one order of magnitude faster compared to the newly developing channel-like porosity structures which act as pathways towards the center of single mineral grains. Thus, it may be possible for the fluid to progress relatively large distances along the grain boundaries after only short reaction durations without producing broad reaction fronts along the path.

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

PubMed Central

Fox, D A; Millard, J A; Kan, L; Zeldes, W S; Davis, W; Higgs, J; Emmrich, F; Kinne, R W

1990-01-01

Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis. Images PMID:2212003

A long-distance fluid transport pathway within fibrous connective tissues in patients with ankle edema.

PubMed

Li, Hongyi; Yang, Chongqing; Lu, Kuiyuan; Zhang, Liyang; Yang, Jiefu; Wang, Fang; Liu, Dongge; Cui, Di; Sun, Mingjun; Pang, Jianxin; Dai, Luru; Han, Dong; Liao, Fulong

2016-10-05

Although the microcirculatory dysfunctions of edema formation are well documented, the draining pattern of dermal edema lacks information. This study was to assess the potential drainage pathways of the interstitial fluid in patients with ankle edema using the anatomical and histological methods. Four amputees of lower leg participated in this study. Fluorescent imaging agent was injected into lateral ankle dermis in one volunteered patient before the amputation and three lower legs after the amputation. Physiologically in the volunteer or enhanced by cyclical compression on three amputated limbs, several fluorescent longitudinal pathways from ankle dermis to the broken end of the amputated legs were subsequently visualized and studied using histological methods, laser confocal microscopy and electron microscopy methods respectively. Interestingly, the fluorescent pathways confirmed to be fibrous connective tissues and the presence of two types: those of the cutaneous pathway (located in dermis or the interlobular septum among adipose tissues within the hypodermis) and those of the perivascular pathway (located in connective tissues surrounding the veins and the arteries). The intrinsic three-dimensional architecture of each fluorescent pathway was the longitudinally running and interconnected fibril bundles, upon which, an interfacial transport pathway within connective tissues was visualized by fluorescein. The current anatomical data suggested that a unique long-distance transport pathway composed of oriented fibrous connective tissues might play a pathophysiological role in draining dermal edema besides vascular circulations and provide novel understandings of general fibrous connective tissues in life science.

Trafficking of glucose, lactate, and amyloid-β from the inferior colliculus through perivascular routes

PubMed Central

Ball, Kelly K; Cruz, Nancy F; Mrak, Robert E; Dienel, Gerald A

2010-01-01

Metabolic brain imaging is widely used to evaluate brain function and disease, and quantitative assays require local retention of compounds used to register changes in cellular activity. As labeled metabolites of [1- and 6-14C]glucose are rapidly released in large quantities during brain activation, this study evaluated release of metabolites and proteins through perivascular fluid flow, a pathway that carries solutes from brain to peripheral lymphatic drainage sites. Assays with [3,4-14C]glucose ruled out local oxidation of glucose-derived lactate as a major contributor of label loss. Brief infusion of [1-14C]glucose and -[14C]lactate into the inferior colliculus of conscious rats during acoustic stimulation labeled the meninges, consistent with perivascular clearance of [14C]metabolites from interstitial fluid. Microinfusion of Evans blue albumin and amyloid-β1−40 (Aβ) caused perivascular labeling in the inferior colliculus, labeled the surrounding meninges, and Aβ-labeled-specific blood vessels in the caudate and olfactory bulb and was deposited in cervical lymph nodes. Efflux of extracellular glucose, lactate, and Aβ into perivascular fluid pathways is a normal route for clearance of material from the inferior colliculus that contributes to underestimates of brain energetics. Convergence of ‘watershed' drainage to common pathways may facilitate perivascular amyloid plaque formation and pathway obstruction in Alzheimer's disease. PMID:19794399

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain.

PubMed

Grinevich, Valery; Knobloch-Bollmann, H Sophie; Eliava, Marina; Busnelli, Marta; Chini, Bice

2016-02-01

Oxytocin (OT) is a neuropeptide, which can be seen to be one of the molecules of the decade due to its profound prosocial effects in nonvertebrate and vertebrate species, including humans. Although OT can be detected in various physiological fluids (blood, saliva, urine, cerebrospinal fluid) and brain tissue, it is unclear whether peripheral and central OT releases match and synergize. Moreover, the pathways of OT delivery to brain regions involved in specific behaviors are far from clear. Here, we discuss the evolutionarily and ontogenetically determined pathways of OT delivery and OT signaling, which orchestrate activity of the mesolimbic social decision-making network. Furthermore, we speculate that both the alteration in OT delivery and OT receptor expression may cause behavioral abnormalities in patients afflicted with psychosocial diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A deep crustal fluid channel into the San Andreas Fault system near Parkfield, California

USGS Publications Warehouse

Becken, M.; Ritter, O.; Park, S.K.; Bedrosian, P.A.; Weckmann, U.; Weber, M.

2008-01-01

Magnetotelluric (MT) data from 66 sites along a 45-km-long profile across the San Andreas Fault (SAF) were inverted to obtain the 2-D electrical resistivity structure of the crust near the San Andreas Fault Observatory at Depth (SAFOD). The most intriguing feature of the resistivity model is a steeply dipping upper crustal high-conductivity zone flanking the seismically defined SAF to the NE, that widens into the lower crust and appears to be connected to a broad conductivity anomaly in the upper mantle. Hypothesis tests of the inversion model suggest that upper and lower crustal and upper-mantle anomalies may be interconnected. We speculate that the high conductivities are caused by fluids and may represent a deep-rooted channel for crustal and/or mantle fluid ascent. Based on the chemical analysis of well waters, it was previously suggested that fluids can enter the brittle regime of the SAF system from the lower crust and mantle. At high pressures, these fluids can contribute to fault-weakening at seismogenic depths. These geochemical studies predicted the existence of a deep fluid source and a permeable pathway through the crust. Our resistivity model images a conductive pathway, which penetrates the entire crust, in agreement with the geochemical interpretation. However, the resistivity model also shows that the upper crustal branch of the high-conductivity zone is located NE of the seismically defined SAF, suggesting that the SAF does not itself act as a major fluid pathway. This interpretation is supported by both, the location of the upper crustal high-conductivity zone and recent studies within the SAFOD main hole, which indicate that pore pressures within the core of the SAF zone are not anomalously high, that mantle-derived fluids are minor constituents to the fault-zone fluid composition and that both the volume of mantle fluids and the fluid pressure increase to the NE of the SAF. We further infer from the MT model that the resistive Salinian block basement to the SW of the SAFOD represents an isolated body, being 5-8km wide and reaching to depths >7km, in agreement with aeromagnetic data. This body is separated from a massive block of Salinian crust farther to the SW. The NE terminus of resistive Salinian crust has a spatial relationship with a near-vertical zone of increased seismic reflectivity ???15km SW of the SAF and likely represents a deep-reaching fault zone. ?? 2008 The Authors Journal compilation ?? 2008 RAS.

Blood Hemostatic Changes During an Ultraendurance Road Cycling Event in a Hot Environment.

PubMed

Kupchak, Brian R; Kazman, Josh B; Vingren, Jakob L; Levitt, Danielle E; Lee, Elaine C; Williamson, Keith H; Armstrong, Lawrence E; Deuster, Patricia A

2017-09-01

This study aims to examine blood hemostatic responses to completing a 164-km road cycling event in a hot environment. Thirty-seven subjects (28 men and 9 women; 51.8±9.5 [mean±SD] y) completed the ride in 6.6±1.1 hours. Anthropometrics (height, body mass [taken also during morning of the ride], percent body fat [%]) were collected the day before the ride. Blood samples were collected on the morning of the ride (PRE) and immediately after (IP) the subject completed the ride. Concentrations of platelet, platelet activation, coagulation, and fibrinolytic markers (platelet factor 4, β-thromboglobulin, von Willebrand factor antigen, thrombin-antithrombin complex, thrombomodulin, and D-Dimer) were measured. Associations between changes from PRE- to IP-ride were examined as a function of event completion time and subject characteristics (demographics and anthropometrics). All blood hemostatic markers increased significantly (P < .001) from PRE to IP. After controlling for PRE values, finishing time was negatively correlated with platelet factor 4 (r = 0.40; P = .017), while percent body fat (%BF) was negatively correlated with thrombin-antithrombin complex (r = -0.35; P = .038) and to thrombomodulin (r = -0.36; P = .036). In addition, male subjects had greater concentrations of thrombin-antithrombin complex (d = 0.63; P < .05) and natural logarithm thrombomodulin (d = 6.42; P < .05) than female subjects. Completing the 164-km road cycling event in hot conditions resulted in increased concentrations of platelet, platelet activation, coagulation, and fibrinolytic markers in both men and women. Although platelet activation and coagulation occurred, the fibrinolytic system markers also increased, which appears to balance blood hemostasis and may prevent clot formation during exercise in a hot environment. Published by Elsevier Inc.

Effect of Ankaferd Blood Stopper on Skin Superoxide Dismutase and Catalase Activities in Warfarin-Treated Rats.

PubMed

Aktop, Sertaç; Emekli-Alturfan, Ebru; Gönül, Onur; Göçmen, Gökhan; Garip, Hasan; Yarat, Ayşen; Göker, Kamil

2017-03-01

Ankaferd Blood Stopper (ABS) is a new promising local hemostatic agent, and its mechanism on hemostasis has been shown by many studies. However, the effects of ABS on skin superoxide dismutase (SOD) and catalase (CAT) activities have not been investigated before. The aim of this study was to evaluate the effects of this new generation local hemostatic agent on warfarin-treated rats focusing on its the antioxidant potential in short-term soft tissue healing. Twelve systemically warfarin treated (warfarin group) and 12 none treated Wistar Albino rats (control group) were selected for the trial. Rats in the warfarin group were treated intraperitonally with 0.1 mg/kg warfarin, and rats in the control group were given 1 mL/kg saline 3 days earlier to surgical procedure and continued until killing. All rats had incisions on dorsal dermal tissue, which was applied ABS or no hemostatic agent before suturing. Six of each group were killed on day 4, and the other 6 were killed on day 8. Blood and skin samples were taken. Prothrombin time (PT) in blood samples, CAT, and SOD activities in skin samples were determined. Warfarin treatment dose was found to be convenient and warfarin treatment increased the PT levels as expected. Warfarin treatment decreased CAT activity significantly compared to the control group. The ABS treatment significantly increased SOD activities in the warfarin group at the end of the eighth day. Ankaferd Blood Stopper acted positively in short-term tissue healing by increasing SOD activity in warfarin-treated rats. Therefore, ABS may be suggeted as a promoting factor in tissue healing.

Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy.

PubMed

Baumgartner, Bernhard; Draxler, Wolfgang; Lewis, Kevin M

2016-12-01

The perioperative management of patients on antithrombotic therapy is currently an unresolved problem as these therapies pose a considerable risk for perioperative hemorrhagic complications. The presented studies investigated the efficacy of a new collagen technology to achieve hemostasis. A polyethylene glycol-coated collagen pad (PCC) was compared to a marketed fibrinogen-thrombin coated collagen pad (FTC) for the treatment of an aortotomy incision in heparinized swine on dual antiplatelet therapy. Twenty-eight 3-mm aortotomy incisions were created in nine heparinized pigs without antiplatelet therapy and treated with PCC. Sixty-eight aortotomy incisions were created in ten heparinized pigs that received clopidogrel (10-11 mg/kg) and acetylsalicylic acid (8-11 mg/kg) orally for 5 days, and treated with either PCC or FTC (N = 34/group). Dual antiplatelet therapy resulted in significantly reduced platelet function. Aortotomy incisions resulted in life-threatening bleeding of 35-292 ml/min. In animals without antiplatelet treatment, PCC provided 96% immediate hemostatic success. In animals with antiplatelet treatment, FTC provided 18% immediate hemostatic success increasing to 74% after 10 min. Strikingly, PCC provided 94% immediate success increasing to 100% after 10 min. Controlling for differences in pretreatment bleeding rates, statistical model-estimated time to hemostasis was 12 times shorter in PCC-treated lesions (p < .02). The combination of a procoagulant collagen pad with a synthetic sealing component provides excellent hemostatic properties under a worst-case scenario. PCC rapidly and firmly adheres to tissue, thereby controlling severe arterial bleeding, even when platelet function is significantly reduced. Treatment with PCC provided superior time to hemostasis compared to FTC.

Hemostatic and toxinological diversities in venom of Micrurus tener tener, Micrurus fulvius fulvius and Micrurus isozonus coral snakes.

PubMed

Salazar, Ana M; Vivas, Jeilyn; Sánchez, Elda E; Rodríguez-Acosta, Alexis; Ibarra, Carlos; Gil, Amparo; Carvajal, Zoila; Girón, María E; Estrella, Amalid; Navarrete, Luis F; Guerrero, Belsy

2011-07-01

The coral snake Micrurus tener tener (Mtt) from the Elapidae family inhabits the southwestern United States and produces severe cases of envenomations. Although the majority of Mtt venom components are neurotoxins and phospholipase A₂s, this study demonstrated, by SDS-PAGE and molecular exclusion chromatography (MEC), that these venoms also contain high-molecular-weight proteins between 50 and 150 kDa that target the hemostatic system. The biological aspects of other Micrurus venoms were also studied, such as the LD₅₀s of Micrurus isozonus (from 0.52 to 0.61 mg/kg). A pool from these venoms presented a LD₅₀ of 0.57 mg/kg, Micrurus f. fulvius (Mff) and Mtt had LD₅₀s of 0.32 and 0.78 mg/kg, respectively. These venoms contained fibrino(geno)lytic activity, they inhibited platelet aggregation, as well as factor Xa and/or plasmin-like activities. M. isozonus venoms from different Venezuelan geographical regions inhibited ADP-induced platelet aggregation (from 50 to 68%). Micrurus tener tener venom from the United States was the most active with a 95.2% inhibitory effect. This venom showed thrombin-like activity on fibrinogen and human plasma. Fractions of Mtt showed fibrino(geno)lytic activity and inhibition on plasmin amidolytic activity. Several fractions degraded the fibrinogen Aα chains, and fractions F2 and F7 completely degraded both fibrinogen Aα and Bβ chains. To our knowledge, this is the first report on thrombin-like and fibrino(geno)lytic activity and plasmin or factor Xa inhibitors described in Micrurus venoms. Further purification and characterization of these Micrurus venom components could be of therapeutic use in the treatment of hemostatic disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

New alternatives for laser vaporization of the prostate: experimental evaluation of a 980-, 1,318- and 1,470-nm diode laser device.

PubMed

Wezel, Felix; Wendt-Nordahl, Gunnar; Huck, Nina; Bach, Thorsten; Weiss, Christel; Michel, Maurice Stephan; Häcker, Axel

2010-04-01

Several diode laser systems were introduced in recent years for the minimal-invasive surgical therapy of benign prostate enlargement. We investigated the ablation capacities, hemostatic properties and extend of tissue necrosis of different diode lasers at wavelengths of 980, 1,318 and 1,470 nm and compared the results to the 120 W GreenLight HPS laser. The laser devices were evaluated in an ex vivo model using isolated porcine kidneys. The weight difference of the porcine kidneys after 10 min of laser vaporization defined the amount of ablated tissue. Blood loss was measured in blood-perfused kidneys following laser vaporization. Histological examination was performed to assess the tissue effects. The side-firing 980 and 1,470 nm diode lasers displayed similar ablative capacities compared to the GreenLight HPS laser (n.s.). The 1,318-nm laser, equipped with a bare-ended fiber, reached a higher ablation rate compared to the other laser devices (each P < 0.05). A calculated 'output power efficiency per watt' revealed that the 1,318-nm laser with a bare-ended fiber reached the highest rate compared to the side-firing devices (each P < 0.0001). All three diode lasers showed superior hemostatic properties compared to the GreenLight HPS laser (each P < 0.01). The extend of morphological tissue necrosis was 4.62 mm (1,318 nm), 1.30 mm (1,470 nm), 4.18 mm (980 nm) and 0.84 mm (GreenLight HPS laser), respectively. The diode lasers offered similar ablative capacities and improved hemostatic properties compared to the 120 W GreenLight HPS laser in this experimental ex vivo setting. The higher tissue penetration of the diode lasers compared to the GreenLight HPS laser may explain improved hemostasis.

Comparison of polyurethane with cyanoacrylate in hemostasis of vascular injury in guinea pigs.

PubMed

Kubrusly, Luiz Fernando; Formighieri, Marina Simões; Lago, José Vitor Martins; Graça, Yorgos Luiz Santos de Salles; Sobral, Ana Cristina Lira; Lago, Marianna Martins

2015-01-01

To evaluate the behavior of castor oil-derived polyurethane as a hemostatic agent and tissue response after abdominal aortic injury and to compare it with 2-octyl-cyanoacrylate. Twenty-four Guinea Pigs were randomly divided into three groups of eight animals (I, II, and III). The infrarenal abdominal aorta was dissected, clamped proximally and distally to the vascular puncture site. In group I (control), hemostasis was achieved with digital pressure; in group II (polyurethane) castor oil-derived polyurethane was applied, and in group III (cyanoacrylate), 2-octyl-cyanoacrylate was used. Group II was subdivided into IIA and IIB according to the time of preparation of the hemostatic agent. Mean blood loss in groups IIA, IIB and III was 0.002 grams (g), 0.008 g, and 0.170 g, with standard deviation of 0.005 g, 0.005 g, and 0.424 g, respectively (P=0.069). The drying time for cyanoacrylate averaged 81.5 seconds (s) (standard deviation: 51.5 seconds) and 126.1 s (standard deviation: 23.0 s) for polyurethane B (P=0.046). However, there was a trend (P=0.069) for cyanoacrylate to dry more slowly than polyurethane A (mean: 40.5 s; SD: 8.6 s). Furthermore, polyurethane A had a shorter drying time than polyurethane B (P=0.003), mean IIA of 40.5 s (standard deviation: 8.6 s). In group III, 100% of the animals had mild/severe fibrosis, while in group II only 12.5% showed this degree of fibrosis (P=0.001). Polyurethane derived from castor oil showed similar hemostatic behavior to octyl-2-cyanoacrylate. There was less perivascular tissue response with polyurethane when compared with cyanoacrylate.

Evaluation of the hemostatic and histopathological effects of Ankaferd Blood Stopper in experimental liver injury in rats.

PubMed

Satar, Nihal Y Gul; Akkoc, Ahmet; Oktay, Ayberk; Topal, Ayse; Inan, Kivanc

2013-07-01

We studied the hemostatic and histopathological effects, and intra-abdominal adhesion scores of a new hemostatic agent, Ankaferd Blood Stopper (ABS), in an experimental liver injury model and compared it with regenerated oxidized cellulose. Thirty-six rats were randomly assigned to ABS, oxidized cellulose (Surgicel), and control groups (n=12, each). A wedge resection was performed on the left medial lobe of the liver. In the ABS group the liver surface was sprayed with ABS, whereas in the Surgicel group the liver was covered with double-layered oxidized cellulose. In the control group, saline solution was sprayed on the cut surface. The mean bleeding time was shorter in the ABS (23.08±6.99s) and Surgicel groups (47.91±8.21s) than in the control group (223.42±57.83s). No significant difference was found in the ABS and Surgicel groups in terms of preoperative and postoperative hematocrit (hct) values (P>0.05). Whereas there was no significant difference on day 7 (P>0.05), total adhesion score of ABS group was lower than both Surgicel (P<0.05) and control groups (P<0.01) on day 14. Liver sections from ABS group displayed more favorable histopathological changes when compared with Surgicel group on day 7 and day 14. All livers in the ABS group completed their regeneration process with minimal signs of inflammation. Our findings suggest that ABS is more effective than Surgicel and control groups in achieving hemostasis and in reducing blood loss. Apart from this, ABS causes more encouraging histopathological changes and better intra-abdominal adhesion scores in rat experimental liver trauma model.

Hemostats, sealants, and adhesives: components of the surgical toolbox.

PubMed

Spotnitz, William D; Burks, Sandra

2008-07-01

The surgical toolbox is expanding, and newer products are being developed to improve results. Reducing blood loss so that bloodless surgery can be performed may help minimize morbidity and length of stay. As patients, hospital administrators, and government regulators desire less invasive procedures, the surgical technical challenge is increasing. More operations are being performed through minimally invasive incisions with laparoscopic, endoscopic, and robotic approaches. In this setting, tools that can reduce bleeding by causing blood to clot, sealing vessels, or gluing tissues are gaining an increasing importance. Thus, hemostats, sealants, and adhesives are becoming a more important element of surgical practice. This review is designed to facilitate the reader's basic knowledge of these tools so that informed choices are made for controlling bleeding in specific clinical situations. Such information is useful for all members of the operative team. The team includes surgeons, anesthesiologists, residents, and nurses as well as hematologists and other medical specialists who may be involved in the perioperative care of surgical patients. An understanding of these therapeutic options may also be helpful to the transfusion service. In some cases, these materials may be stored in the blood bank, and their appropriate use may reduce demand for other transfusion components. The product classification used in this review includes hemostats as represented by product categories that include mechanical agents, active agents, flowables, and fibrin sealants; sealants as represented by fibrin sealants and polyethylene glycol hydrogels; and adhesives as represented by cyanoacrylates and albumin cross-linked with glutaraldehyde. Only those agents approved by the Food and Drug Administration (FDA) and presently available (February 2008) for sale in the United States are discussed in this review.

Predicting the severity of systemic inflammatory response syndrome (SIRS)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers.

PubMed

Iba, Toshiaki; Gando, Satoshi; Murata, Atsuo; Kushimoto, Shigeki; Saitoh, Daizoh; Eguchi, Yutaka; Ohtomo, Yasuhiro; Okamoto, Kohji; Koseki, Kazuhide; Mayumi, Toshihiko; Ikeda, Toshiaki; Ishhikura, Hiroyasu; Ueyama, Masashi; Ogura, Yuji; Endo, Shigeatsu; Shimazaki, Shuji

2007-11-01

The changes in biomarkers of coagulation or fibrinolysis, anticoagulation, inflammation, and endothelial damage occur in patients with systemic inflammatory response syndrome (SIRS). The purpose of this study is to assess the prognostic value of these markers in patients with SIRS-associated hypercoagulopathy. Sixty-six SIRS patients with a platelet count less than 15.0 x 10(4)/mm3 in three university hospital intensive care units were enrolled in this prospective, comparative study. Blood samples were obtained on day 0 and day 2. Twelve hemostatic, inflammatory, and vascular endothelial indices were measured and the data were compared between the severe group (patients with a total maximum Sequential Organ Failure Assessment score of 10 or more and nonsurvivors; n = 25) and the less-severe group (Sequential Organ Failure Assessment score <10; n = 41). Significant changes between the groups were observed in platelet count, fibrin or fibrinogen degradation products, interleukin-6, soluble thrombomodulin, antithrombin (AT) activity, and protein C activity, both on day 0 and on day 2. In contrast, the d-dimer, soluble fibrin, plasmin-[alpha]2-antiplasmin complex, and E-selectin levels were higher in the severe group only on day 2. No significant difference was seen regarding the thrombin-AT complex and total plasminogen activator inhibitor on both days. A comparison of the areas under the receiver operating characteristic curve revealed the AT activity to be the best predictor of a progression of organ dysfunction. The changes in some hemostatic molecular markers and vascular endothelial markers were conspicuous in patients with organ dysfunction. The AT activity is considered to be the most useful predictor of organ dysfunction.

Comparison of polyurethane with cyanoacrylate in hemostasis of vascular injury in guinea pigs

PubMed Central

Kubrusly, Luiz Fernando; Formighieri, Marina Simões; Lago, José Vitor Martins; Graça, Yorgos Luiz Santos de Salles; Sobral, Ana Cristina Lira; Lago, Marianna Martins

2015-01-01

Objective To evaluate the behavior of castor oil-derived polyurethane as a hemostatic agent and tissue response after abdominal aortic injury and to compare it with 2-octyl-cyanoacrylate. Methods Twenty-four Guinea Pigs were randomly divided into three groups of eight animals (I, II, and III). The infrarenal abdominal aorta was dissected, clamped proximally and distally to the vascular puncture site. In group I (control), hemostasis was achieved with digital pressure; in group II (polyurethane) castor oil-derived polyurethane was applied, and in group III (cyanoacrylate), 2-octyl-cyanoacrylate was used. Group II was subdivided into IIA and IIB according to the time of preparation of the hemostatic agent. Results Mean blood loss in groups IIA, IIB and III was 0.002 grams (g), 0.008 g, and 0.170 g, with standard deviation of 0.005 g, 0.005 g, and 0.424 g, respectively (P=0.069). The drying time for cyanoacrylate averaged 81.5 seconds (s) (standard deviation: 51.5 seconds) and 126.1 s (standard deviation: 23.0 s) for polyurethane B (P=0.046). However, there was a trend (P=0.069) for cyanoacrylate to dry more slowly than polyurethane A (mean: 40.5 s; SD: 8.6 s). Furthermore, polyurethane A had a shorter drying time than polyurethane B (P=0.003), mean IIA of 40.5 s (standard deviation: 8.6 s). In group III, 100% of the animals had mild/severe fibrosis, while in group II only 12.5% showed this degree of fibrosis (P=0.001). Conclusion Polyurethane derived from castor oil showed similar hemostatic behavior to octyl-2-cyanoacrylate. There was less perivascular tissue response with polyurethane when compared with cyanoacrylate. PMID:25859876

Numerical modeling of fracking fluid migration through fault zones and fractures in the North German Basin

NASA Astrophysics Data System (ADS)

Pfunt, Helena; Houben, Georg; Himmelsbach, Thomas

2016-09-01

Gas production from shale formations by hydraulic fracturing has raised concerns about the effects on the quality of fresh groundwater. The migration of injected fracking fluids towards the surface was investigated in the North German Basin, based on the known standard lithology. This included cases with natural preferential pathways such as permeable fault zones and fracture networks. Conservative assumptions were applied in the simulation of flow and mass transport triggered by a high pressure boundary of up to 50 MPa excess pressure. The results show no significant fluid migration for a case with undisturbed cap rocks and a maximum of 41 m vertical transport within a permeable fault zone during the pressurization. Open fractures, if present, strongly control the flow field and migration; here vertical transport of fracking fluids reaches up to 200 m during hydraulic fracturing simulation. Long-term transport of the injected water was simulated for 300 years. The fracking fluid rises vertically within the fault zone up to 485 m due to buoyancy. Progressively, it is transported horizontally into sandstone layers, following the natural groundwater flow direction. In the long-term, the injected fluids are diluted to minor concentrations. Despite the presence of permeable pathways, the injected fracking fluids in the reported model did not reach near-surface aquifers, either during the hydraulic fracturing or in the long term. Therefore, the probability of impacts on shallow groundwater by the rise of fracking fluids from a deep shale-gas formation through the geological underground to the surface is small.

Influence of mantle viscosity structure and mineral grain size on fluid migration pathways in the mantle wedge.

NASA Astrophysics Data System (ADS)

Cerpa, N. G.; Wada, I.; Wilson, C. R.; Spiegelman, M. W.

2016-12-01

We develop a 2D numerical porous flow model that incorporates both grain size distribution and matrix compaction to explore the fluid migration (FM) pathways in the mantle wedge. Melt generation for arc volcanism is thought to be triggered by slab-derived fluids that migrate into the hot overlying mantle and reduce its melting temperature. While the narrow location of the arcs relative to the top of the slab ( 100±30 km) is a robust observation, the release of fluids is predicted to occur over a wide range of depth. Reconciling such observations and predictions remains a challenge for the geodynamic community. Fluid transport by porous flow depends on the permeability of the medium which in turn depends on fluid fraction and mineral grain size. The grain size distribution in the mantle wedge predicted by laboratory derived laws was found to be a possible mechanism to focusing of fluids beneath the arcs [Wada and Behn, 2015]. The viscous resistance of the matrix to the volumetric strain generates compaction pressure that affects fluid flow and can also focus fluids towards the arc [Wilson et al, 2014]. We thus have developed a 2D one-way coupled Darcy's-Stokes flow model (solid flow independent of fluid flow) for the mantle wedge that combines both effects. For the solid flow calculation, we use a kinematic-dynamic approach where the system is driven by the prescribed slab velocity. The solid rheology accounts for both dislocation and diffusion creep and we calculate the grain size distribution following Wada and Behn [2015]. In our fluid flow model, the permeability of the medium is grain size dependent and the matrix bulk viscosity depends on solid shear viscosity and fluid fraction. The fluid influx from the slab is imposed as a boundary condition at the base of the mantle wedge. We solve the discretized governing equations using the software package TerraFERMA. Applying a range of model parameter values, including slab age, slab dip, subduction rate, and fluid influx, we quantify the combined effects of grain size and compaction on fluid flow paths.

Proteomic analysis of Bombyx mori molting fluid: Insights into the molting process.

PubMed

Liu, Hua-Wei; Wang, Luo-Ling; Tang, Xin; Dong, Zhao-Ming; Guo, Peng-Chao; Zhao, Dong-Chao; Xia, Qing-You; Zhao, Ping

2018-02-20

Molting is an essential biological process occurring multiple times throughout the life cycle of most Ecdysozoa. Molting fluids accumulate and function in the exuvial space during the molting process. In this study, we used liquid chromatography-tandem mass spectrometry to investigate the molting fluids to analyze the molecular mechanisms of molting in the silkworm, Bombyx mori. In total, 375 proteins were identified in molting fluids from the silkworm at 14-16h before pupation and eclosion, including 12 chitin metabolism-related enzymes, 35 serine proteases, 15 peptidases, and 38 protease inhibitors. Gene ontology analysis indicated that "catalytic" constitutes the most enriched function in the molting fluid. Gene expression patterns and bioinformatic analyses suggested that numerous enzymes are involved in the degradation of cuticle proteins and chitin. Protein-protein interaction network and activity analyses showed that protease inhibitors are involved in the regulation of multiple pathways in molting fluid. Additionally, many immune-related proteins may be involved in the immune defense during molting. These results provide a comprehensive proteomic insight into proteolytic enzymes and protease inhibitors in molting fluid, and will likely improve the current understanding of physiological processes in insect molting. Insect molting constitutes a dynamic physiological process. To better understand this process, we used LC-MS/MS to investigate the proteome of silkworm molting fluids and identified key proteins involved in silkworm molting. The biological processes of the old cuticle degradation pathway and immune defense response were analyzed in the proteome of silkworm molting fluid. We report that protease inhibitors serve as key factors in the regulation of the molting process. The proteomic results provide new insight into biological molting processes in insects. Copyright © 2017 Elsevier B.V. All rights reserved.

Absorbable Antimicrobial Battlefield Hemostat

DTIC Science & Technology

2013-04-01

to graphene sheet and carbon nanotubes . Coupled with ABTS, the GQDs can be used for the detection of hydrogen peroxide with the limit of detection......dressing could be made of any material that is compatible to our coating solvent. Examples include gelatin based and cellulose based substrates. The

The effects of BleedArrest on hemorrhage control in a porcine model.

PubMed

Gegel, Brian; Burgert, James; Loughren, Michael; Johnson, Don

2012-01-01

The purpose of this study was to examine the effectiveness of the hemostatic agent BleedArrest compared to control. This was a prospective, experimental design employing an established porcine model of uncontrolled hemorrhage. The minimum number of animals (n=10 per group) was used to obtain a statistically valid result. There were no statistically significant differences between the groups (P>.05) indicating that the groups were equivalent on the following parameters: activating clotting time, the subject weights, core body temperatures, amount of one minute hemorrhage, arterial blood pressures, and the amount and percentage of total blood volume. There were significant differences in the amount of hemorrhage (P=.033) between the BleedArrest (mean=72, SD±72 mL) and control (mean=317.30, SD±112.02 mL). BleedArrest is statistically and clinically superior at controlling hemorrhage compared to the standard pressure dressing control group. In conclusion, BleedArrest is an effective hemostatic agent for use in civilian and military trauma management.

Adhesive and robust multilayered poly(lactic acid) nanosheets for hemostatic dressing in liver injury model.

PubMed

Komachi, Takuya; Sumiyoshi, Hideaki; Inagaki, Yutaka; Takeoka, Shinji; Nagase, Yu; Okamura, Yosuke

2017-10-01

Freestanding biodegradable nanosheets composed of poly(l-lactic acid) (PLLA) have been developed for various biomedical applications. These nanosheets exhibit unique properties such as high adhesiveness and exquisite flexibility; however, they burst easily due to their nanometer thickness. We herein describe a freestanding, multilayered nanosheet composed of PLLA fabricated using a simple combination procedure: (i) multilayering of PLLA and alginate, (ii) gelation of the alginate layers, (iii) fusion-cut sealing, and (iv) elution of the alginate layers. The multilayered nanosheets not only reinforced the bursting strength but also provided a high level of adhesive strength. In fact, they were found to show potential as a hemostatic dressing, and they tended to show reduced tissue adhesion that accompanies liver injury. Therefore, we propose this biomaterial as a candidate for an alternative to conventional therapy in hemorrhage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1747-1757, 2017. © 2016 Wiley Periodicals, Inc.

Comparative Evaluation of Biological Performance, Biosecurity, and Availability of Cellulose-Based Absorbable Hemostats.

PubMed

Wu, Yadong; Wang, Fang; Huang, Yudong

2018-05-01

Hemorrhage remains a leading cause of death after trauma, and developing a hemostat with excellent performance and good biosecurity is an extremely active area of research and commercial product development. Although oxidized regenerated cellulose (ORC) has been developed to address these problems, it is not always efficient and its biosecurity is not perfect. We aimed to refine ORC via a simple and mild neutralization method. The prepared neutralized oxidized regenerated cellulose (NORC) showed a superior gel property due to its chemical structure. The biological performance of both ORC and NORC was systematically evaluated; the results showed that ORC would induce erythema and edema in the irritation test, whereas NORC did not cause any adverse inflammation, indicating NORC had desirable biocompatibility. We further demonstrated that NORC confirmed to the toxicity requirements of International Organization for Standardization (ISO) standards; however, ORC showed an unacceptable cytotoxicity. The rabbit hepatic defect model stated that NORC exhibited better ability of hemostasis, which was attributed to its significant gel performance in physiological environment.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

PubMed

Iliff, Jeffrey J; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-03-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

PubMed Central

Iliff, Jeffrey J.; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-01-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer’s disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer’s disease susceptibility and progression in the live human brain. PMID:23434588

Quantification and Control of Wall Effects in Porous Media Experiments

NASA Astrophysics Data System (ADS)

Roth, E. J.; Mays, D. C.; Neupauer, R.; Crimaldi, J. P.

2017-12-01

Fluid flow dynamics in porous media are dominated by media heterogeneity. This heterogeneity can create preferential pathways in which local seepage velocities dwarf system seepage velocities, further complicating an already incomplete understanding of dispersive processes. In physical models of porous media flows, apparatus walls introduce preferential flow paths (i.e., wall effects) that may overwhelm other naturally occurring preferential pathways within the apparatus, leading to deceptive results. We used planar laser-induced fluorescence (PLIF) in conjunction with refractive index matched (RIM) porous media and pore fluid to observe fluid dynamics in the porous media, with particular attention to the region near the apparatus walls in a 17 cm x 8 cm x 7 cm uniform flow cell. Hexagonal close packed spheres were used to create an isotropic, homogenous porous media field in the interior of the apparatus. Visualization of the movement of a fluorescent dye revealed the influence of the wall in creating higher permeability preferential flow paths in an otherwise homogenous media packing. These preferential flow paths extended approximately one half of one sphere diameter from the wall for homogenously packed regions, with a quickly diminishing effect on flow dynamics for homogenous media adjacent to the preferential pathway, but with major influence on flow dynamics for adjoining heterogeneous regions. Multiple approaches to mitigate wall effects were investigated, and a modified wall was created such that the fluid dynamics near the wall mimics the fluid dynamics within the homogenous porous media. This research supports the design of a two-dimensional experimental apparatus that will simulate engineered pumping schemes for use in contaminant remediation. However, this research could benefit the design of fixed bed reactors or other engineering challenges in which vessel walls contribute to unwanted preferential flow.

Iron Transformation Pathways and Redox Micro-Environments in Seafloor Sulfide-Mineral Deposits: Spatially Resolved Fe XAS and δ(57/54)Fe Observations.

PubMed

Toner, Brandy M; Rouxel, Olivier J; Santelli, Cara M; Bach, Wolfgang; Edwards, Katrina J

2016-01-01

Hydrothermal sulfide chimneys located along the global system of oceanic spreading centers are habitats for microbial life during active venting. Hydrothermally extinct, or inactive, sulfide deposits also host microbial communities at globally distributed sites. The main goal of this study is to describe Fe transformation pathways, through precipitation and oxidation-reduction (redox) reactions, and examine transformation products for signatures of biological activity using Fe mineralogy and stable isotope approaches. The study includes active and inactive sulfides from the East Pacific Rise 9°50'N vent field. First, the mineralogy of Fe(III)-bearing precipitates is investigated using microprobe X-ray absorption spectroscopy (μXAS) and X-ray diffraction (μXRD). Second, laser-ablation (LA) and micro-drilling (MD) are used to obtain spatially-resolved Fe stable isotope analysis by multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS). Eight Fe-bearing minerals representing three mineralogical classes are present in the samples: oxyhydroxides, secondary phyllosilicates, and sulfides. For Fe oxyhydroxides within chimney walls and layers of Si-rich material, enrichments in both heavy and light Fe isotopes relative to pyrite are observed, yielding a range of δ(57)Fe values up to 6‰. Overall, several pathways for Fe transformation are observed. Pathway 1 is characterized by precipitation of primary sulfide minerals from Fe(II)aq-rich fluids in zones of mixing between vent fluids and seawater. Pathway 2 is also consistent with zones of mixing but involves precipitation of sulfide minerals from Fe(II)aq generated by Fe(III) reduction. Pathway 3 is direct oxidation of Fe(II) aq from hydrothermal fluids to form Fe(III) precipitates. Finally, Pathway 4 involves oxidative alteration of pre-existing sulfide minerals to form Fe(III). The Fe mineralogy and isotope data do not support or refute a unique biological role in sulfide alteration. The findings reveal a dynamic range of Fe transformation pathways consistent with a continuum of micro-environments having variable redox conditions. These micro-environments likely support redox cycling of Fe and S and are consistent with culture-dependent and -independent assessments of microbial physiology and genetic diversity of hydrothermal sulfide deposits.

CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt pathway by regulating the proliferation and invasion of ESCs.

PubMed

Diao, Ruiying; Wei, Weixia; Zhao, Jinghui; Tian, Fuying; Cai, Xueyong; Duan, Yong-Gang

2017-11-01

The level of CCL19 increased in the peritoneal fluid of women with endometriosis, but the precise mechanism of CCL19/CCR7 in the pathogenesis of endometriosis remains unknown. ELISA and immunohistochemistry were performed to analyze CCL19/CCR7 expressions in peritoneal fluid and endometrium from women with endometriosis (n = 38) and controls (n = 32). Cell proliferation and transwell invasion assays were applied to detect proliferation and invasion of human endometrial stromal cells (ESCs). Expressions of Bcl2, MMP2, MMP9, and p-AKT/AKT were analyzed by Western blot. Peritoneal fluid concentration of CCL19 in patients with endometriosis was higher than that in controls. Those patients with moderate/severe endometriosis had significantly higher peritoneal fluid concentrations of CCL19 compared to those with minimal/mild endometriosis. Higher CCL19 and CCR7 were found in the endometrium with endometriosis compared to control. CCL19 significantly enhanced ESC proliferation and invasion through CCR7 via activating PI3K/Akt signal pathways. CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, Bcl2, MMP2, and MMP9 in ESCs. These data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evidence for natural molecular hydrogen seepage associated with Carolina bays (surficial, ovoid depressions on the Atlantic Coastal Plain, Province of the USA)

NASA Astrophysics Data System (ADS)

Zgonnik, Viacheslav; Beaumont, Valérie; Deville, Eric; Larin, Nikolay; Pillot, Daniel; Farrell, Kathleen M.

2015-12-01

A study of soil gases was made in North Carolina (USA) in and around morphological depressions called "Carolina bays." This type of depression is observed over the Atlantic coastal plains of the USA, but their origin remains debated. Significant concentrations of molecular hydrogen (H2) were detected, notably around the bays. These measurements suggest that Carolina bays are the surficial expression of fluid flow pathways for hydrogen gas moving from depth to the surface. The potential mechanisms of H2 production and transport and the geological controls on the fluid migration pathways are discussed, with reference to the hypothesis that Carolina bays are the result of local collapses caused by the alteration of rock along the deep pathways of H2 migrating towards the surface. The present H2 seepages are comparable to those in similar structures previously observed in the East European craton.

Absorbable Antimicrobial Battlefield Hemostat

DTIC Science & Technology

2012-10-01

image of SiNFs after reation with GA The SiNFs were sonicated for 5mins to achieve homogenous dispersion in water, and then mixed with gentamicin...of coagulation (typical activated clotting times of whole pigs blood using a kaolin clay activator are approximately 90 seconds, in the absence of

Acute Traumatic Coagulopathy

DTIC Science & Technology

2014-12-01

therapeutic approaches are discussed, including viscoelastic coagulation monitoring and the role of tranexamic acid and blood products. Summary...and tranexamic acid in addition to red cell units in order to reduce bleeding and improve clinical outcomes. Keywords acute traumatic coagulopathy...endothelial activation, fibrinolysis, hemostatic resuscitation, hypoperfusion, microparticles, platelet dysfunction, tranexamic acid , viscoelastic

Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways

PubMed Central

Bedussi, Beatrice; van der Wel, Nicole N; de Vos, Judith; van Veen, Henk; Siebes, Maria; VanBavel, Ed

2016-01-01

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid. PMID:27306753

Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways.

PubMed

Bedussi, Beatrice; van der Wel, Nicole N; de Vos, Judith; van Veen, Henk; Siebes, Maria; VanBavel, Ed; Bakker, Erik Ntp

2017-04-01

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid.

Mapping the Fluid Pathways and Permeability Barriers of a Large Gas Hydrate Reservoir

NASA Astrophysics Data System (ADS)

Campbell, A.; Zhang, Y. L.; Sun, L. F.; Saleh, R.; Pun, W.; Bellefleur, G.; Milkereit, B.

2012-12-01

An understanding of the relationship between the physical properties of gas hydrate saturated sedimentary basins aids in the detection, exploration and monitoring one of the world's upcoming energy resources. A large gas hydrate reservoir is located in the MacKenzie Delta of the Canadian Arctic and geophysical logs from the Mallik test site are available for the gas hydrate stability zone (GHSZ) between depths of approximately 850 m to 1100 m. The geophysical data sets from two neighboring boreholes at the Mallik test site are analyzed. Commonly used porosity logs, as well as nuclear magnetic resonance, compressional and Stoneley wave velocity dispersion logs are used to map zones of elevated and severely reduced porosity and permeability respectively. The lateral continuity of horizontal permeability barriers can be further understood with the aid of surface seismic modeling studies. In this integrated study, the behavior of compressional and Stoneley wave velocity dispersion and surface seismic modeling studies are used to identify the fluid pathways and permeability barriers of the gas hydrate reservoir. The results are compared with known nuclear magnetic resonance-derived permeability values. The aim of investigating this heterogeneous medium is to map the fluid pathways and the associated permeability barriers throughout the gas hydrate stability zone. This provides a framework for an understanding of the long-term dissociation of gas hydrates along vertical and horizontal pathways, and will improve the knowledge pertaining to the production of such a promising energy source.

Report on von Willebrand Disease in Malaysia

PubMed Central

Periayah, Mercy Halleluyah; Halim, Ahmad Sukari; Saad, Arman Zaharil Mat; Yaacob, Nik Soriani; Karim, Faraizah Abdul

2016-01-01

BACKGROUND: Von Willebrand disease (vWD) is an inherited hemostatic disorder that affects the hemostasis pathway. The worldwide prevalence of vWD is estimated to be 1% of the general population but only 0.002% in Malaysia. AIM: Our present paper has been written to disclose the statistical counts on the number of vWD cases reported from 2011 to 2013. MATERIAL AND METHODS: This article is based on sociodemographic data, diagnoses and laboratory findings of vWD in Malaysia. A total of 92 patients were reported to have vWD in Malaysia from 2011 to 2013. RESULTS: Sociodemographic-analysis revealed that 60% were females, 63% were of the Malay ethnicity, 41.3% were in the 19-44 year old age group and 15.2% were from Sabah, with the East region having the highest registered number of vWD cases. In Malaysia, most patients are predominately affected by vWD type 1 (77.2%). Factor 8, von Willebrand factor: Antigen and vWF: Collagen-Binding was the strongest determinants in the laboratory profiles of vWD. CONCLUSION: This report has been done with great interest to provide an immense contribution from Malaysia, by revealing the statistical counts on vWD from 2011-2013. PMID:27275342

The origin and function of platelet glycosyltransferases

PubMed Central

Rumjantseva, Viktoria; Sørensen, Anne Louise Tølbøll; Patel-Hett, Sunita; Josefsson, Emma C.; Bennett, Eric P.; Italiano, Joseph E.; Clausen, Henrik; Hartwig, John H.; Hoffmeister, Karin M.

2012-01-01

Platelets are megakaryocyte subfragments that participate in hemostatic and host defense reactions and deliver pro- and antiangiogenic factors throughout the vascular system. Although they are anucleated cells that lack a complex secretory apparatus with distinct Golgi/endoplasmic reticulum compartments, past studies have shown that platelets have glycosyltransferase activities. In the present study, we show that members of 3 distinct glycosyltransferase families are found within and on the surface of platelets. Immunocytology and flow cytometry results indicated that megakaryocytes package these Golgi-derived glycosyltransferases into vesicles that are sent via proplatelets to nascent platelets, where they accumulate. These glycosyltransferases are active, and intact platelets glycosylate large exogenous substrates. Furthermore, we show that activation of platelets results in the release of soluble glycosyltransferase activities and that platelets contain sufficient levels of sugar nucleotides for detection of glycosylation of exogenously added substrates. Therefore, the results of the present study show that blood platelets are a rich source of both glycosyltransferases and donor sugar substrates that can be released to function in the extracellular space. This platelet-glycosylation machinery offers a pathway to a simple glycoengineering strategy improving storage of platelets and may serve hitherto unknown biologic functions. PMID:22613794

Self-organizing maps in geothermal exploration-A new approach for understanding geochemical processes and fluid evolution

NASA Astrophysics Data System (ADS)

Brehme, Maren; Bauer, Klaus; Nukman, Mochamad; Regenspurg, Simona

2017-04-01

Understanding geochemical processes is an important part of geothermal exploration to get information about the source and evolution of geothermal fluids. However, in most cases knowledge of fluid properties is based on few parameters determined in samples from the shallow subsurface. This study presents a new approach that allows to conclude from the combination of a variety of these data on processes occurring at depth in a geothermal reservoir. The neural network clustering technique called "self-organizing maps" (SOMs) successfully distinguished two different geothermal settings based on a hydrochemical database and disclosed the source, evolution and flow pathways of geothermal fluids. Scatter plots, as shown in this study, are appropriate presentations of element concentrations and the chemical interaction of water and rock at depth. One geological setting presented here is marked by fault dominated fluid pathways and minor influence of volcanic affected fluids with high concentrations of HCO3, Ca and Sr. The second is a magmatically dominated setting showing strong alteration features in volcanic rocks and accommodates acidic fluids with high SO4 and Si concentrations. Former studies, i.e., Giggenbach (1988), suggested Cl, HCO3 and SO4 to be generally the most important elements for understanding hydrochemical processes in geothermal reservoirs. Their relation has been widely used to classify different water types in geothermal fields. However, this study showed that non-standard elements are at least of same importance to reveal different fluid types in geothermal systems. Therefore, this study is an extended water classification approach using SOM for element correlations. SOM have been proven to be a successful method for analyzing even relatively small hydrochemical datasets in geothermal applications.

Disruption of estrogen receptor signaling and similar pathways in the efferent ductules and initial segment of the epididymis

PubMed Central

Hess, Rex A

2014-01-01

Abstract: Seminiferous tubular atrophy may involve indirectly the disruption of estrogen receptor-α (ESR1) function in efferent ductules of the testis. ESR1 helps to maintain fluid resorption by the ductal epithelium and the inhibition or stimulation of this activity in rodent species will lead to fluid accumulation in the lumen. If not resolved, the abnormal buildup of fluid in the head of the epididymis and efferent ductules becomes a serious problem for the testis, as it leads to an increase in testis weight, tubular dilation and seminiferous epithelial degeneration, as well as testicular atrophy. The same sequence of pathogenesis occurs if the efferent ductule lumen becomes occluded. This review provides an introduction to the role of estrogen in the male reproductive tract but focuses on the various overlapping mechanisms that could induce efferent ductule dysfunction and fluid backpressure histopathology. Although efferent ductules are difficult to find, their inclusion in routine histological evaluations is recommended, as morphological images of these delicate tubules may be essential for understanding the mechanism of testicular injury, especially if dilations are observed in the rete testis and/or seminiferous tubules. Signature Lesion: The rete testis and efferent ductules can appear dilated, as if the lumens were greatly expanded with excess fluid or the accumulation of sperm. Because the efferent ductules resorb most of the fluid arriving from the rete testis lumen, one of two mechanisms is likely to be involved: a) reduced fluid uptake, which has been caused by the disruption in estrogen receptor signaling or associated pathways; or b) an increased rate of fluid resorption, which results in luminal occlusion. Both mechanisms can lead to a temporary increase in testicular weight, tubular dilation and atrophy of the seminiferous tubules. PMID:26413389

Disruption of estrogen receptor signaling and similar pathways in the efferent ductules and initial segment of the epididymis.

PubMed

Hess, Rex A

2014-01-01

Seminiferous tubular atrophy may involve indirectly the disruption of estrogen receptor-α (ESR1) function in efferent ductules of the testis. ESR1 helps to maintain fluid resorption by the ductal epithelium and the inhibition or stimulation of this activity in rodent species will lead to fluid accumulation in the lumen. If not resolved, the abnormal buildup of fluid in the head of the epididymis and efferent ductules becomes a serious problem for the testis, as it leads to an increase in testis weight, tubular dilation and seminiferous epithelial degeneration, as well as testicular atrophy. The same sequence of pathogenesis occurs if the efferent ductule lumen becomes occluded. This review provides an introduction to the role of estrogen in the male reproductive tract but focuses on the various overlapping mechanisms that could induce efferent ductule dysfunction and fluid backpressure histopathology. Although efferent ductules are difficult to find, their inclusion in routine histological evaluations is recommended, as morphological images of these delicate tubules may be essential for understanding the mechanism of testicular injury, especially if dilations are observed in the rete testis and/or seminiferous tubules. Signature Lesion : The rete testis and efferent ductules can appear dilated, as if the lumens were greatly expanded with excess fluid or the accumulation of sperm. Because the efferent ductules resorb most of the fluid arriving from the rete testis lumen, one of two mechanisms is likely to be involved: a) reduced fluid uptake, which has been caused by the disruption in estrogen receptor signaling or associated pathways; or b) an increased rate of fluid resorption, which results in luminal occlusion. Both mechanisms can lead to a temporary increase in testicular weight, tubular dilation and atrophy of the seminiferous tubules.

Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury.

PubMed

Deng, Wang; Li, Chang-Yi; Tong, Jin; Zhang, Wei; Wang, Dao-Xin

2012-03-30

Stimulation of epithelial sodium channel (ENaC) increases Na(+) transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.

Syn-metamorphic interconnected porosity during blueschist facies reactive fluid fluxes at the slab-mantle interface

NASA Astrophysics Data System (ADS)

Konrad-Schmolke, Matthias; Klitscher, Nicolai; Halama, Ralf; Wirth, Richard; Morales, Luiz

2017-04-01

At the slab-mantle interface in subdution zones fluids released from the downgoing plate infiltrate into a mechanical mixture of rocks with different chemical compositions, different hydration states and different rheological behaviour resulting in a highly reactive mélange within a steep temperature gradient. Fluid pathways, reaction mechanisms and reaction rates of such fluxes, however, are poorly known, although these parameters are thought to be crucial for several seismic phenomena, such as those commonly referred to as slow earthquakes (e.g., episodic tremor and slip (ETS)). We discovered syn-metamorphic fluid-pathways in the form of interconnected metamorphic porosity in eclogite and blueschist facies mélange rocks from the Franciscan Complex near Jenner, CA. The sampled rocks occur as rigid mafic blocks of different sizes (cm to decametre) in a weak chlorite-serpentine matrix interpreted to be an exhumed slab-mantle interface. Some of these mafic blocks record reactive fluid infiltration that transforms dry eclogite into hydrous blueschist with a sharp reaction front clearly preserved and visible from outcrop- down to µm-scale. We can show that a number of interconnected fluid pathways, such as interconnected metamorphic porosity between reacting omphacite and newly formed sodic amphibole enabled fluid infiltration and interface coupled solution-reprecipitation reactions at blueschist facies conditions. We investigated the different types of fluid pathways with TEM and visualized their interconnectivity with 3D focused ion beam (FIB) sections. The eclogitic parts of the samples preserve porous primary omphacite as a product of amphibole and epidote breakdown during subduction. This primary porosity in omphacite I results from a negative volume change in the solids during amphibole and epidote dehydration. The resulting pores appear as (fluid filled) elongated inclusions the orientations of which are controlled by the omphacite lattice. During decompression of the rocks these inclusions became interconnected by brittle fractures that allowed a first fluid influx and the precipitation of new omphacite (II) within the fracture network and along the rims of the primary omphacite. The (second) metamorphic/metasomatic porosity occurs along the reaction surfaces between omphacite and sodic amphibole as well as within omphacite grains where new omphacite (III) is formed. This interconnected pore network associated with the re-hydration reaction is up to 1µm but mostly between 50 and 200nm wide. Reacting omphacite is preferentially consumed in 00-1 direction and has a rugged, often needle-like surface. In contrast, product surfaces (omphacite III and sodic amphibole) are relatively smooth indicating dissolution of older omphacite (I and II) and re-precipitation of omphacite III as well as the formation of sodic amphibole. Within some of the pores amorphous silica-rich material containing smaller amounts of Al, Ca, Fe and Mg, can be found as worm-like precipitates and as coatings on top of the needle-like omphacite surface. Phase relations, textures as well as overprinting relations clearly show that the porosity is syn-metamorphic under blueschist-facies conditions. Although difficult to constrain in the samples porosity is likely between 1-5 volume%.

Can serpentinization induce fracturing? Fluid pathway development and the volume increase enigma

NASA Astrophysics Data System (ADS)

Plümper, Oliver; Jamtveit, Bjørn; Røyne, Anja

2013-04-01

Serpentinization of ultramafic rocks has first-order effects on global element cycles, the rheology of the oceanic lithosphere, plays a key role in plate tectonics by lubricating subduction zones and has been linked to the origin of life due to the creation of abiogenic hydrocarbons. In addition, the capability of ultramafic rocks to safely store enormous amounts of carbon dioxide through mineral reactions may provide a unique solution to fight global warming. However, all the aforementioned processes are reliant on the creation and maintenance of fluid pathways to alter an originally impermeable rock. Although the forces that move tectonic plates can produce these fluid pathways by mechanical fracturing, there is ample evidence that serpentinization reactions can 'eat' their way through a rock. This process is facilitated by solid volume changes during mineral reactions that cause expansion, fracturing the rock to generate fluid pathways. Natural observations of serpentinization/carbonation in ultramafic rocks indicate that the associated positive solid volume change alone exerts enough stress on the surrounding rock to build up a fracture network and that the influence of external tectonic forces is not necessary. Through various feedbacks these systems can either become self-sustaining, when an interconnected fracture network is formed, or self-limiting due to fluid pathway obstruction. However, extensively serpentinized outcrops suggest that although crystal growth in newly opened spaces would reduce permeability, serpentinization is not always self-limiting as porosity generation can occur concomitantly, maintaining or even increasing permeability. This is consistent with theory and demonstrates that fluids transported through fracture networks can alter vast amounts of originally impermeable rock. Nevertheless, whether serpentinization can actually generate these fracture networks is still a matter of debate and only a few scientific investigations have focused on this topic so far. Here, we investigate the feasibility of reaction-induced fracturing and pore space evolution during serpentinization by combining microstructural investigations using scanning/transmission electron microscopy and synchrotron micro-tomography of natural samples with theoretical considerations on the forces exerted during solid volume increasing reactions. We particularly focus on the interface-scale mechanism of reaction-induced fracturing (Plümper et al. 2012) and the establishment of microstructural markers (e.g., inert exsolutions in olivine) to identify volume changes and estimate crystallization pressures (Kelemen and Hirth 2012). Our investigations suggest that reaction-induced fracturing during serpentinization is possible and during certain physico-chemical circumstances a positive feedback to alter vast amounts of originally impermeable rock is established. Plümper O., Røyne A., Magraso A., Jamtveit B. (2012) The interface-scale mechanism of reaction-induced fracturing during serpentinization. Geology. 40, 1103-1106. Kelemen, P. B. & Hirth, G. (2012) Reaction-driven cracking during retrograde metamorphism: Olivine hydration and carbonation. Earth and Planetary Science Letters 345, 81-89.

77 FR 8271 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... Institute Special Emphasis Panel; Planning Studies for Rare Thrombotic and Hemostatic Disorders. Date: March... Nos. 93.233, National Center for Sleep Disorders Research; 93.837, Heart and Vascular Diseases Research; 93.838, Lung Diseases Research; 93.839, Blood Diseases and Resources Research, National...

Management of External Hemorrhage in Tactical Combat Casualty Care: Chitosan-Based Hemostatic Gauze Dressings. TCCC Guidelines Change 13-05

DTIC Science & Technology

2014-09-23

dramatically decreased. Coagulation parameters improved significantly over the next 36 hours. Muzzi et al./2012 CEG Acute prosthetic endocarditis ; 4 months...prosthetic endocarditis ; 4 months post aortic dissection surgery Preoperative IV heparin with impaired coagulation state. Yes; discharged

Improving on Army Field Gauze for Lethal Vascular Injuries: Challenges in Dressing Development

USDA-ARS?s Scientific Manuscript database

Accounting for half of all deaths, uncontrolled hemorrhage remains the leading cause of death on the battlefield. Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model compared a...

Electrokinetic and hemostatic profiles of nonwoven cellulosic/ synthetic fiber blends with unbleached cotton

USDA-ARS?s Scientific Manuscript database

Greige cotton contains waxes and pectin on the outer surface of the fiber that are removed from bleached cotton, but present added potential for wound dressing functionality. Innovations to mechanically clean and sterilize greige cotton (or non-bleached cotton) do not remove these exterior componen...

A Novel Swine Model for Evaluation of Potential Intravascular Hemostatic Agents

DTIC Science & Technology

2007-06-01

bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock 24:145–152. 2. Bellamy RF. 1984. The causes of death in...WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. 2005. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J

In vitro hemostatic, hydrogen peroxide production and elastase sequestration properties of nonwoven ultra clean greige cotton dressing

USDA-ARS?s Scientific Manuscript database

Nonwoven UltraCleanTM Cotton (highly cleaned and hydroentangled, greige cotton) retains the native wax and pectin content (~2%) of the cotton fiber traditionally removed from scoured and bleached cotton gauze, yet potentially affording wound healing properties. In vitro thromboelastography, hydrog...

Holmium: yttrium aluminum garnet laser-assisted endoscopic sinus surgery: laboratory experience.

PubMed

Shapshay, S M; Rebeiz, E E; Bohigian, R K; Hybels, R L; Aretz, H T; Pankratov, M M

1991-02-01

Endoscopic sinus surgery has gained wide acceptance since its introduction into the United States. Complex sinus anatomy and troublesome bleeding have been associated with complications, which vary in severity from synechia to blindness and leakage of cerebrospinal fluid. Endoscopic sinus surgery using a holmium: yttrium aluminum garnet pulsed solid-state laser oscillating at 2.1 microns with fiberoptic delivery was performed in the laboratory, and the results were compared with those of conventional endoscopic sinus surgery. Three beagle dogs, six human cadaver heads, and one calf head were used in the in vivo and in vitro studies to evaluate the bone ablation, tissue coagulation, and hemostatic properties of the holmium: yttrium aluminum garnet laser. Modified endoscopic telescopes for sinus surgery, a newly developed handpiece for fiberoptic delivery, and other surgical instruments were used. The results indicate that the holmium: yttrium aluminum garnet laser and new delivery instrumentation provide good hemostasis and controlled soft-tissue ablation and bone removal. The access to all sinuses in the human cadaver model was very good. The canine in vivo study showed delayed but complete healing on the laser-treated side. Clinical evaluation of the holmium: yttrium aluminum garnet laser is warranted to increase the precision and safety of endoscopic sinus surgery.

Ruptured renal arteriovenous malformation successfully treated by catheter embolization: a case report.

PubMed

Takeuchi, Nobuhiro; Nomura, Yusuke

2014-01-09

Renal arteriovenous fistula (RAVF) is a comparatively rare malformation. Here, we report a case of ruptured RAVF that was successfully treated by catheter embolization. An 89-year-old female was transferred to our institution with massive gross hematuria in March 2011. Plain abdominal computed tomography (CT) revealed dilated left renal pelvis with high-density contents. Hematoma was suspected. Subsequent plain abdominal magnetic resonance imaging revealed left hydronephrosis and blood retention in the dilated left renal pelvis. No renal or ureteral cancer was evident. Hematuria was conservatively treated using hemostatic agents but hematuria persisted. Repeated urinary cytology revealed no malignant cells. On day 9, the patient went into septic and/or hemorrhagic shock. Fluid and catecholamine infusion, blood transfusion, and antibacterial drugs were rapidly initiated, and the patient's general condition gradually improved. Contrast-enhanced abdominal CT revealed marked expansion of the hematoma in the renal pelvis and microaneurysms in the segmental arteries of the left kidney. Inflammation improved, and a left double-J stent was inserted. Selective renal angiography revealed RAVF with microaneurysms in the left segmental arteries; therefore, catheter embolization using metallic coils was performed, which resolved hematuria. We report a case of ruptured renal arteriovenous malformation, which was successfully treated by catheter embolization.

Water pollution risk associated with natural gas extraction from the Marcellus Shale.

PubMed

Rozell, Daniel J; Reaven, Sheldon J

2012-08-01

In recent years, shale gas formations have become economically viable through the use of horizontal drilling and hydraulic fracturing. These techniques carry potential environmental risk due to their high water use and substantial risk for water pollution. Using probability bounds analysis, we assessed the likelihood of water contamination from natural gas extraction in the Marcellus Shale. Probability bounds analysis is well suited when data are sparse and parameters highly uncertain. The study model identified five pathways of water contamination: transportation spills, well casing leaks, leaks through fractured rock, drilling site discharge, and wastewater disposal. Probability boxes were generated for each pathway. The potential contamination risk and epistemic uncertainty associated with hydraulic fracturing wastewater disposal was several orders of magnitude larger than the other pathways. Even in a best-case scenario, it was very likely that an individual well would release at least 200 m³ of contaminated fluids. Because the total number of wells in the Marcellus Shale region could range into the tens of thousands, this substantial potential risk suggested that additional steps be taken to reduce the potential for contaminated fluid leaks. To reduce the considerable epistemic uncertainty, more data should be collected on the ability of industrial and municipal wastewater treatment facilities to remove contaminants from used hydraulic fracturing fluid. © 2012 Society for Risk Analysis.

Pulsatile Fluid Shear in Bone Remodeling

NASA Technical Reports Server (NTRS)

Frangos, John A.

1997-01-01

The objective of this investigation was to elucidate the sensitivity to transients in fluid shear stress in bone remodeling. Bone remodeling is clearly a function of the local mechanical environment which includes interstitial fluid flow. Traditionally, load-induced remodeling has been associated with low frequency (1-2 Hz) signals attributed to normal locomotion. McLeod and Rubin, however, demonstrated in vivo remodeling events associated with high frequency (15-30 Hz) loading. Likewise, other in vivo studies demonstrated that slowly applied strains did not trigger remodeling events. We therefore hypothesized that the mechanosensitive pathways which control bone maintenance and remodeling are differentially sensitive to varying rates of applied fluid shear stress.

Freeform Fluidics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Love, Lonnie J; Richardson, Bradley S; Lind, Randall F

This work explores the integration of miniaturized fluid power and additive manufacturing. Oak Ridge National Laboratory (ORNL) has been developing an approach to miniaturized fluidic actuation and control that enables high dexterity, low cost and a pathway towards energy efficiency. Previous work focused on mesoscale digital control valves (high pressure, low flow) and the integration of actuation and fluid passages directly with the structure. The primary application being fluid powered robotics. The fundamental challenge was part complexity. Additive manufacturing technologies (E-Beam, Laser and Ultrasonic deposition) enable freeform manufacturing using conventional metal alloys with excellent mechanical properties. The combination of thesemore » two technologies (miniaturized fluid power and additive manufacturing) can enable a paradigm shift in fluid power, increasing efficiency while simultaneously reducing weight, size, complexity and cost.« less

Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

PubMed Central

Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

2013-01-01

Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toner, Brandy M.; Rouxel, Olivier J.; Santelli, Cara M.

Hydrothermal sulfide chimneys located along the global system of oceanic spreading centers are habitats for microbial life during active venting. Hydrothermally extinct, or inactive, sulfide deposits also host microbial communities at globally distributed sites. The main goal of this study is to describe Fe transformation pathways, through precipitation and oxidation-reduction (redox) reactions, and examine transformation products for signatures of biological activity using Fe mineralogy and stable isotope approaches. The study includes active and inactive sulfides from the East Pacific Rise 9°50'N vent field. First, the mineralogy of Fe(III)-bearing precipitates is investigated using microprobe X-ray absorption spectroscopy (μXAS) and X-ray diffractionmore » (μXRD). Second, laser-ablation (LA) and micro-drilling (MD) are used to obtain spatially-resolved Fe stable isotope analysis by multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS). Eight Fe-bearing minerals representing three mineralogical classes are present in the samples: oxyhydroxides, secondary phyllosilicates, and sulfides. For Fe oxyhydroxides within chimney walls and layers of Si-rich material, enrichments in both heavy and light Fe isotopes relative to pyrite are observed, yielding a range of δ 57Fe values up to 6‰. Overall, several pathways for Fe transformation are observed. Pathway 1 is characterized by precipitation of primary sulfide minerals from Fe(II)aq-rich fluids in zones of mixing between vent fluids and seawater. Pathway 2 is also consistent with zones of mixing but involves precipitation of sulfide minerals from Fe(II)aq generated by Fe(III) reduction. Pathway 3 is direct oxidation of Fe(II) aq from hydrothermal fluids to form Fe(III) precipitates. Finally, Pathway 4 involves oxidative alteration of pre-existing sulfide minerals to form Fe(III). The Fe mineralogy and isotope data do not support or refute a unique biological role in sulfide alteration. The findings reveal a dynamic range of Fe transformation pathways consistent with a continuum of micro-environments having variable redox conditions. Lastly, these micro-environments likely support redox cycling of Fe and S and are consistent with culture-dependent and -independent assessments of microbial physiology and genetic diversity of hydrothermal sulfide deposits.« less

Application of the amniotic fluid metabolome to the study of fetal malformations, using Down syndrome as a specific model.

PubMed

Huang, Jun; Mo, Jinhua; Zhao, Guili; Lin, Qiyin; Wei, Guanhui; Deng, Weinan; Chen, Dunjin; Yu, Bolan

2017-11-01

Although monitoring and diagnosis of fetal diseases in utero remains a challenge, metabolomics may provide an additional tool to study the etiology and pathophysiology of fetal diseases at a functional level. In order to explore specific markers of fetal disease, metabolites were analyzed in two separate sets of experiments using amniotic fluid from fetuses with Down syndrome (DS) as a model. Both sets included 10‑15 pairs of controls and cases, and amniotic fluid samples were processed separately; metabolomic fingerprinting was then conducted using UPLC‑MS. Significantly altered metabolites involved in respective metabolic pathways were compared in the two experimental sets. In addition, significantly altered metabolic pathways were further compared with the genomic characters of the DS fetuses. The data suggested that metabolic profiles varied across different experiments, however alterations in the 4 metabolic pathways of the porphyrin metabolism, bile acid metabolism, hormone metabolism and amino acid metabolism, were validated for the two experimental sets. Significant changes in metabolites of coproporphyrin III, glycocholic acid, taurochenodeoxycholate, taurocholate, hydrocortisone, pregnenolone sulfate, L‑histidine, L‑arginine, L‑glutamate and L‑glutamine were further confirmed. Analysis of these metabolic alterations was linked to aberrant gene expression at chromosome 21 of the DS fetus. The decrease in coproporphyrin III in the DS fetus may portend abnormal erythropoiesis, and unbalanced glutamine‑glutamate concentration was observed to be closely associated with abnormal brain development in the DS fetus. Therefore, alterations in amniotic fluid metabolites may provide important clues to understanding the etiology of fetal disease and help to develop diagnostic testing for clinical applications.

Non-invasive, transdermal, path-selective and specific glucose monitoring via a graphene-based platform

NASA Astrophysics Data System (ADS)

Lipani, Luca; Dupont, Bertrand G. R.; Doungmene, Floriant; Marken, Frank; Tyrrell, Rex M.; Guy, Richard H.; Ilie, Adelina

2018-06-01

Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and `quantized' glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.

Physical Activity in Older Men: Longitudinal Associations with Inflammatory and Hemostatic Biomarkers, N-Terminal Pro-Brain Natriuretic Peptide, and Onset of Coronary Heart Disease and Mortality

PubMed Central

Jefferis, Barbara J; Whincup, Peter H; Lennon, Lucy T; Papacosta, Olia; Goya Wannamethee, S

2014-01-01

Objectives To examine associations between habitual physical activity (PA) and changes in PA and onset of coronary heart disease (CHD) and the pathways linking PA to CHD. Design British Regional Heart Study population-based cohort; men completed questionnaires in 1996 and 1998 to 2000, attended rescreen in 1998 to 2000, and were followed up to June 2010. Setting Community. Participants Of 4,252 men recruited from primary care centers (77% of those invited and eligible) who were rescreened in 1998 to 2000, 3,320 were ambulatory and free from CHD, stroke, and heart failure and participated in the current study. Measurements Usual PA (regular walking and cycling, recreational activity and sport). Outcome was first fatal or nonfatal myocardial infarction. Results In 3,320 ambulatory men, 303 first and 184 fatal CHD events occurred during a median of 11 years of follow-up; 9% reported no usual PA, 23% occasional PA, and 68% light or more-intense PA. PA was inversely associated with novel risk markers C-reactive protein, D-dimer, von Willebrand Factor and N-terminal pro-brain natriuretic peptide (NT-proBNP). Compared with no usual PA, hazard ratios (HRs) for CHD events, adjusted for age and region, were 0.52 (95% confidence interval (CI) = 0.34–0.79) for occasional PA, 0.47 (95% CI = 0.30–0.74) for light PA, 0.51 (95% CI = 0.32–0.82) for moderate PA, and 0.44 (95% CI = 0.29–0.65) for moderately vigorous or vigorous PA (P for linear trend = .004). Adjustment for established and novel risk markers somewhat attenuated HRs and abolished linear trends. Compared with men who remained inactive, men who maintained at least light PA had an HR for CHD events of 0.73 (95% CI = 0.53–1.02) and men whose PA level increased had an HR of 0.86 (95% CI = 0.55–1.35). Conclusion Even light PA was associated with significantly lower risk of CHD events in healthy older men, partly through inflammatory and hemostatic mechanisms and cardiac function (NT-proBNP). PMID:24635212

Leptospira Immunoglobulin-Like Protein B (LigB) Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking.

PubMed

Hsieh, Ching-Lin; Chang, Eric; Tseng, Andrew; Ptak, Christopher; Wu, Li-Chen; Su, Chun-Li; McDonough, Sean P; Lin, Yi-Pin; Chang, Yung-Fu

2016-09-01

The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.

Leptospira Immunoglobulin-Like Protein B (LigB) Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking

PubMed Central

Hsieh, Ching-Lin; Chang, Eric; Tseng, Andrew; Ptak, Christopher; Wu, Li-Chen; Su, Chun-Li; McDonough, Sean P.; Lin, Yi-Pin; Chang, Yung-Fu

2016-01-01

The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis. PMID:27622634

Postoperative nausea and vomiting after unrestricted clear fluids before day surgery: A retrospective analysis.

PubMed

McCracken, Graham C; Montgomery, Jane

2018-05-01

Guidance on pre-operative fluids fasting policy continues to evolve. Current European guidelines encourage the intake of oral fluids up to 2 h before the induction of general anaesthesia. From October 2014, Torbay Hospital Day Surgery Unit commenced an unrestricted fluid policy, encouraging patients to drink clear fluids up until the time of transfer to theatre. The aim of this study was to assess the incidence of postoperative nausea and vomiting before and after the change to the unrestricted pre-operative clear oral fluids. Retrospective, before and after study. Single district general hospital between November 2013 and February 2016. A total of 11 500 patients on the day case pathway who were receiving either sedation, general anaesthesia, regional anaesthesia or their combination. The data from these patients were collected routinely. This number of patients represents approximately 78% of all patients before the change in fluids policy and 74% after the change. Exclusions were patients undergoing a termination of pregnancy, or patients undergoing community dental procedures, from whom patient experience data are not collected. Introduction of a change to the day surgery pathway policy permitting unrestricted clear oral fluids preoperatively until transfer to theatre (from October 2014). Incidence of postoperative nausea and vomiting. The rates of nausea within 24 h postoperatively were 270/5192 (5.2%) when patients could not drink within 2 h of surgery, and 179/4724 (3.8%) when patients could drink up until surgery, a relative rate (95% confidence interval) of 0.73 (0.61 to 0.88), P = 0.00074. The corresponding rates of vomiting were 146/5186 (2.8%) and 104/4716 (2.2%), a relative rate (95% confidence interval) of 0.78 (0.61 to 1.00), P = 0.053. Our data suggest that the liberal consumption of clear fluids before the induction of scheduled day case anaesthesia reduced the rates of postoperative nausea and vomiting.

Determination of Efficacy of New Hemostatic Dressings in a Model of Extremity Arterial Hemorrhage in Swine

DTIC Science & Technology

2009-09-01

a few milliliters of 2% lidocaine to relax vasospasm and dilate the artery to its normal size. To measure wound temperature, a microelectrode was...clotting function than the untreated samples. The other chitosan product, Celox-D was also found to be ineffective despite successful results with this

Investigating the role of charge on cotton materials designed to intervene in the hemostatic and inflammatory stages of wound healing

USDA-ARS?s Scientific Manuscript database

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and haemostatic phases of wound healing. Hemostasis and inflammation comprise two overlap...

Positively and Negatively Charged Ionic Modifications to Cellulose Assessed as Cotton-Based Protease-Lowering and Haemostatic Wound Agents

USDA-ARS?s Scientific Manuscript database

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and hemostatic phases of wound healing. Hemostasis and inflammation comprise two overlapp...

Bioresponsive Materials for Drug Delivery Based on Carboxymethyl Chitosan/Poly(γ-Glutamic Acid) Composite Microparticles

PubMed Central

Yan, Xiaoting; Tong, Zongrui; Chen, Yu; Mo, Yanghe; Feng, Huaiyu; Li, Peng; Qu, Xiaosai; Jin, Shaohua

2017-01-01

Carboxymethyl chitosan (CMCS) microparticles are a potential candidate for hemostatic wound dressing. However, its low swelling property limits its hemostatic performance. Poly(γ-glutamic acid) (PGA) is a natural polymer with excellent hydrophilicity. In the current study, a novel CMCS/PGA composite microparticles with a dual-network structure was prepared by the emulsification/internal gelation method. The structure and thermal stability of the composite were determined by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The effects of preparation conditions on the swelling behavior of the composite were investigated. The results indicate that the swelling property of CMCS/PGA composite microparticles is pH sensitive. Levofloxacin (LFX) was immobilized in the composite microparticles as a model drug to evaluate the drug delivery performance of the composite. The release kinetics of LFX from the composite microparticles with different structures was determined. The results suggest that the CMCS/PGA composite microparticles are an excellent candidate carrier for drug delivery. PMID:28452963

[Topical hemostatic devices in surgery: between science and marketing].

PubMed

González, Héctor Daniel; Figueras Felip, Joan

2009-06-01

Topical hemostatic agents have been used in surgery with varying degrees of success. These agents include oxidized cellulose, absorbable gelatin sponges, microfibrillar collagen and fibrin seals. Fibrin seals have become widely used as they improve perioperative hemostasis, reduce the need for red blood cell transfusions and prevent biliary leaks. Their widespread use, however, contrasts with the scarcity of data from controlled studies to support their clinical effectiveness. Therefore, a prospective, randomized, controlled, single-center study was performed in 300 patients who underwent elective hepatectomy, with and without application of fibrin seal on the raw liver surface. None of the variables evaluated (blood loss, transfusions, biliary fistulas and postoperative results) differed between the two groups. We conclude that the application of fibrin seal does not seem justified and that discontinuing its routine use would substantially reduce costs. The use of a new agent, Tachosil, is supported by a single multicenter, prospective, randomized, controlled trial, which is limited by the small number of patients and by the fact that the variable analyzed--time from application to hemostasis--may not be clinically relevant.

Providing Hemostatic and Blood Conservation Options for Jehovah's Witness Patients in a Large Medical System.

PubMed

Bai, Yu; Castillo, Brian S; Tchakarov, Amanda; Escobar, Miguel A; Cotton, Bryan A; Holcomb, John B; Brown, Robert E

2016-12-01

People of the Jehovah's Witness faith believe that they shall "abstain from blood." Because of this belief, we encounter the challenges from Jehovah's Witness patients who actively seek medical care for themselves and their children, but refuse the transfusion of blood products, which may result in increased morbidity and mortality in this patient population. With the development/availability of new hemostatic/coagulation products and the advances in medical technology, we, in collaboration with our clinical colleagues and our local Jehovah's Witness leadership, have developed a clinical guideline comprising medical protocol and surgical strategy for patients refusing blood products. Included in the medical protocol is an informative handout on related details to help treating physicians and patients make informed decisions about transfusion alternatives. Together, we have entered the medical protocol into the entire Memorial Hermann Hospital's electronic system. We report the detailed development and implementation process in order to share our experience and encourage others to develop their own management plan for this patient population. © 2016 by the Association of Clinical Scientists, Inc.

A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots.

PubMed

Seo, Junyoung; Al-Hilal, Taslim A; Jee, Jun-Goo; Kim, Yong-Lim; Kim, Ha-Jeong; Lee, Byung-Heon; Kim, Soyoun; Kim, In-San

2018-04-01

The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin-fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors. Importantly, activated CLT-sFt-μPn thrombolytic nanocage showed a prolonged circulatory life over activated-μPn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-μPn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

DIFFERENTIAL EFFECTS OF EPSILON-AMINOCAPROIC ACID AND APROTININ ON MATRIX METALLOPROTEINASE RELEASE IN PATIENTS FOLLOWING CARDIOPULMONARY BYPASS

PubMed Central

Dorman, Bruce H.; Stroud, Robert E.; Wyckoff, Michael M.; Zellner, James L.; Botta, Don; Leonardi, Amy H.; Ikonomidis, John S.; Spinale, Francis G.

2009-01-01

This study examined whether differential effects of two agents commonly used for hemostatic purposes during cardiac surgery, aprotinin or epsilon-aminocaproic acid (EACA), exist with respect to elevations in proinflammatory interleukins (ILs) and matrix metalloproteinases (MMPs) in patients undergoing coronary artery bypass surgery. Sixty patients were prospectively randomized to receive either aprotinin (1×106 KIU;n=30) or EACA (5gIV;n=30) and blood samples were obtained for IL and MMP levels just before induction of anesthesia (Baseline), 10 minutes after separation from cardiopulmonary bypass (Post) and 6 Hours after surgery (6 Hours). IL-6 was increased at Post in the EACA group and increased further at 6 hours. In the aprotinin group, IL-6 was significantly increased only at 6 Hours. MMP subtypes associated with inflammation, MMP-8 and -9 were increased in the EACA group at Post and remained elevated at 6 Hours. Thus, differential effects on IL and MMP release occurred between aprotinin and EACA, indicative of different mechanisms of action independent of hemostatic effects. PMID:18427286

Modulation of Interleukins in Sepsis-Associated Clotting Disorders: Interplay With Hemostatic Derangement.

PubMed

Low, Christopher; Syed, Daneyal; Khan, Daniel; Tetik, Sermin; Walborn, Amanda; Hoppensteadt, Debra; Mosier, Michael; Fareed, Jawed

2017-01-01

Interleukins play a central role in the immune system and are involved in a variety of immunological, inflammatory, and infectious disease states including sepsis syndrome. Levels of interleukins may correlate with overall survival and may directly or indirectly affect some of the regulators of coagulation and fibrinolysis, thereby disrupting hemostasis and thrombosis. Our hypothesis is that in sepsis-associated coagulopathies (SACs), interleukins may be upregulated, leading to hemostatic imbalance by generating thrombogenic mediators. We profiled the levels of interleukins IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10 in addition to d-dimer (DD) in patients with SAC and in normal donors. We observed the highest increase in interleukins IL-6 (322-fold), IL-8 (48-fold), IL-10 (72-fold), and DD (18-fold). This suggests that interleukins such as IL-6 and IL-10 have a close association with coagulopathy and fibrinolytic dysregulation in sepsis and can be considered as candidates for potential therapeutic targets in SAC. © The Author(s) 2016.

Impact of surgery for endometriomas on pregnancy outcomes following in vitro fertilization-intracytoplasmic sperm injection. Who should be the preferred laparoscopists: gynecologists or reproductive surgeons?

PubMed

Cai, He; Guan, Jing; Shen, Huan; Han, Hongjing; Yu, Xiaoming

2017-08-01

To investigate whether laparoscopic excision of ovarian endometriomas pretreated with operation by gynecologists or reproductive surgeons exerts different effects on in vitro fertilization-intracytoplasmic sperm injection results. Retrospective case control study. Relevant information was collected from the electronic records of women who underwent IVF/ICSI from 01/01/2013 to 30/12/2015 in our unit. The study group consisted of 35 women who previously had laparoscopic endometrioma excision by reproductive surgeons in our unit; the control group included 36 patients who underwent surgery for endometriomas by gynecologists in our hospital. There were slightly higher numbers of AFC and higher pregnancy rate in the study group, although differences did not reach statistical significance. For patients over 35 years old, there were more oocyte retrieved, mature oocytes and two pronucei (2PN) in the study group than the control group although observed differences did not reach statistical significance. Electrocautery is more deleterious on ovarian reserve than hemostatic suture. In procedure of patients who wish to conceive, surgeons should use hemostatic suturing technique preferentially.

Novel thrombin and factor Xa inhibitors: challenges to reversal of their anticoagulation effects.

PubMed

Yates, Sean; Sarode, Ravi

2013-11-01

Warfarin has been the sole oral anticoagulant used in the management of thromboembolic disorders for over 60 years. Target-specific oral anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because they do not require laboratory monitoring. Nevertheless, with the rising use of TSOAs, there is growing concern among clinicians regarding management of bleeding in patients taking them. Unlike warfarin, there is no antidote or reversal agent for TSOAs. This review summarizes recent developments and attempts to provide a systematic approach to patients on TSOAs presenting with bleeding complications. Currently, data involving clinical management of TSOAs are limited and primarily based on ex-vivo or animal models using hemostatic agents with uncertain implications in bleeding patients. There is a pressing need for randomized clinical trials evaluating the safety and efficacy of hemostatic agents. Without evidence-based guidelines for TSOA management, appropriate patient care requires an understanding of TSOA pharmacology, their effect on coagulation tests and, hence, a correct interpretation of test results, as well as a systematic approach to bleeding complications.

Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress.

PubMed

Triacca, Valentina; Güç, Esra; Kilarski, Witold W; Pisano, Marco; Swartz, Melody A

2017-04-28

The transport of interstitial fluid and solutes into lymphatic vessels is important for maintaining interstitial homeostasis and delivering antigens and soluble factors to the lymph node for immune surveillance. Transendothelial transport across lymphatic endothelial cells (LECs) is commonly considered to occur paracellularly, or between cell-cell junctions, and driven by local pressure and concentration gradients. However, emerging evidence suggests that LECs also play active roles in regulating interstitial solute balance and can scavenge and store antigens, raising the possibility that vesicular or transcellular pathways may be important in lymphatic solute transport. The aim of this study was to determine the relative importance of transcellular (vesicular) versus paracellular transport pathways by LECs and how mechanical stress (ie, fluid flow conditioning) alters either pathway. We demonstrate that transcellular transport mechanisms substantially contribute to lymphatic solute transport and that solute uptake occurs in both caveolae- and clathrin-coated vesicles. In vivo, intracelluar uptake of fluorescently labeled albumin after intradermal injection by LECs was similar to that of dermal dendritic cells. In vitro, we developed a method to differentially quantify intracellular solute uptake versus transendothelial transport by LECs. LECs preconditioned to 1 µm/s transmural flow demonstrated increased uptake and basal-to-apical solute transport, which could be substantially reversed by blocking dynamin-dependent vesicle formation. These findings reveal the importance of intracellular transport in steady-state lymph formation and suggest that LECs use transcellular mechanisms in parallel to the well-described paracellular route to modulate solute transport from the interstitium according to biomechanical cues. © 2017 American Heart Association, Inc.

Exosomal and Non-Exosomal Transport of Extra-Cellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence

PubMed Central

Sohel, Md. Mahmodul Hasan; Hoelker, Michael; Noferesti, Sina Seifi; Salilew-Wondim, Dessie; Tholen, Ernst; Looft, Christian; Rings, Franca; Uddin, Muhammad Jasim; Spencer, Thomas E.; Schellander, Karl; Tesfaye, Dawit

2013-01-01

Cell-cell communication within the follicle involves many signaling molecules, and this process may be mediated by secretion and uptake of exosomes that contain several bioactive molecules including extra-cellular miRNAs. Follicular fluid and cells from individual follicles of cattle were grouped based on Brilliant Cresyl Blue (BCB) staining of the corresponding oocytes. Both Exoquick precipitation and differential ultracentrifugation were used to separate the exosome and non-exosomal fraction of follicular fluid. Following miRNA isolation from both fractions, the human miRCURY LNA™ Universal RT miRNA PCR array system was used to profile miRNA expression. This analysis found that miRNAs were present in both exosomal and non-exosomal fraction of bovine follicular fluid. We found 25 miRNAs differentially expressed (16 up and 9 down) in exosomes and 30 miRNAs differentially expressed (21 up and 9 down) in non-exosomal fraction of follicular fluid in comparison of BCB- versus BCB+ oocyte groups. Expression of selected miRNAs was detected in theca, granulosa and cumulus oocyte complex. To further explore the potential roles of these follicular fluid derived extra-cellular miRNAs, the potential target genes were predicted, and functional annotation and pathway analysis revealed most of these pathways are known regulators of follicular development and oocyte growth. In order to validate exosome mediated cell-cell communication within follicular microenvironment, we demonstrated uptake of exosomes and resulting increase of endogenous miRNA level and subsequent alteration of mRNA levels in follicular cells in vitro. This study demonstrates for the first time, the presence of exosome or non-exosome mediated transfer of miRNA in the bovine follicular fluid, and oocyte growth dependent variation in extra-cellular miRNA signatures in the follicular environment. PMID:24223816

Iron Transformation Pathways and Redox Micro-Environments in Seafloor Sulfide-Mineral Deposits: Spatially Resolved Fe XAS and δ57/54Fe Observations

PubMed Central

Toner, Brandy M.; Rouxel, Olivier J.; Santelli, Cara M.; Bach, Wolfgang; Edwards, Katrina J.

2016-01-01

Hydrothermal sulfide chimneys located along the global system of oceanic spreading centers are habitats for microbial life during active venting. Hydrothermally extinct, or inactive, sulfide deposits also host microbial communities at globally distributed sites. The main goal of this study is to describe Fe transformation pathways, through precipitation and oxidation-reduction (redox) reactions, and examine transformation products for signatures of biological activity using Fe mineralogy and stable isotope approaches. The study includes active and inactive sulfides from the East Pacific Rise 9°50′N vent field. First, the mineralogy of Fe(III)-bearing precipitates is investigated using microprobe X-ray absorption spectroscopy (μXAS) and X-ray diffraction (μXRD). Second, laser-ablation (LA) and micro-drilling (MD) are used to obtain spatially-resolved Fe stable isotope analysis by multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS). Eight Fe-bearing minerals representing three mineralogical classes are present in the samples: oxyhydroxides, secondary phyllosilicates, and sulfides. For Fe oxyhydroxides within chimney walls and layers of Si-rich material, enrichments in both heavy and light Fe isotopes relative to pyrite are observed, yielding a range of δ57Fe values up to 6‰. Overall, several pathways for Fe transformation are observed. Pathway 1 is characterized by precipitation of primary sulfide minerals from Fe(II)aq-rich fluids in zones of mixing between vent fluids and seawater. Pathway 2 is also consistent with zones of mixing but involves precipitation of sulfide minerals from Fe(II)aq generated by Fe(III) reduction. Pathway 3 is direct oxidation of Fe(II) aq from hydrothermal fluids to form Fe(III) precipitates. Finally, Pathway 4 involves oxidative alteration of pre-existing sulfide minerals to form Fe(III). The Fe mineralogy and isotope data do not support or refute a unique biological role in sulfide alteration. The findings reveal a dynamic range of Fe transformation pathways consistent with a continuum of micro-environments having variable redox conditions. These micro-environments likely support redox cycling of Fe and S and are consistent with culture-dependent and -independent assessments of microbial physiology and genetic diversity of hydrothermal sulfide deposits. PMID:27242685

Iron transformation pathways and redox micro-environments in seafloor sulfide-mineral deposits: Spatially resolved Fe XAS and δ 57/54Fe observations

DOE PAGES

Toner, Brandy M.; Rouxel, Olivier J.; Santelli, Cara M.; ...

2016-05-10

Hydrothermal sulfide chimneys located along the global system of oceanic spreading centers are habitats for microbial life during active venting. Hydrothermally extinct, or inactive, sulfide deposits also host microbial communities at globally distributed sites. The main goal of this study is to describe Fe transformation pathways, through precipitation and oxidation-reduction (redox) reactions, and examine transformation products for signatures of biological activity using Fe mineralogy and stable isotope approaches. The study includes active and inactive sulfides from the East Pacific Rise 9°50'N vent field. First, the mineralogy of Fe(III)-bearing precipitates is investigated using microprobe X-ray absorption spectroscopy (μXAS) and X-ray diffractionmore » (μXRD). Second, laser-ablation (LA) and micro-drilling (MD) are used to obtain spatially-resolved Fe stable isotope analysis by multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS). Eight Fe-bearing minerals representing three mineralogical classes are present in the samples: oxyhydroxides, secondary phyllosilicates, and sulfides. For Fe oxyhydroxides within chimney walls and layers of Si-rich material, enrichments in both heavy and light Fe isotopes relative to pyrite are observed, yielding a range of δ 57Fe values up to 6‰. Overall, several pathways for Fe transformation are observed. Pathway 1 is characterized by precipitation of primary sulfide minerals from Fe(II)aq-rich fluids in zones of mixing between vent fluids and seawater. Pathway 2 is also consistent with zones of mixing but involves precipitation of sulfide minerals from Fe(II)aq generated by Fe(III) reduction. Pathway 3 is direct oxidation of Fe(II) aq from hydrothermal fluids to form Fe(III) precipitates. Finally, Pathway 4 involves oxidative alteration of pre-existing sulfide minerals to form Fe(III). The Fe mineralogy and isotope data do not support or refute a unique biological role in sulfide alteration. The findings reveal a dynamic range of Fe transformation pathways consistent with a continuum of micro-environments having variable redox conditions. Lastly, these micro-environments likely support redox cycling of Fe and S and are consistent with culture-dependent and -independent assessments of microbial physiology and genetic diversity of hydrothermal sulfide deposits.« less

Heart rate variability, hemostatic and acute inflammatory blood parameters in healthy adults after short-term exposure to welding fume.

PubMed

Scharrer, E; Hessel, H; Kronseder, A; Guth, W; Rolinski, B; Jörres, R A; Radon, K; Schierl, R; Angerer, P; Nowak, D

2007-02-01

The present study aimed to investigate, whether short-term experimental exposure to high levels of welding fumes would be capable of exerting acute effects in healthy subjects. Specifically, we assessed cardiovascular function in terms of heart rate variability (HRV) as well as the concentrations of inflammatory mediators and hemostatic proteins in blood as outcome measures. Twenty subjects without a history of airway and cardiovascular diseases were exposed to either control air or welding fume for 1 h on 2 separate days under standardized conditions. The median concentration of the alveolar particle fraction during welding was 3.5 mg/m(3 )(quartiles: 1.4-6.3 mg/m(3); range 1.0-25.3 mg/m(3)). Five hours later a panel of clinical assessments was performed, including HRV measurement and drawing of blood samples. There were no changes in symptom ratings or lung function after welding fume exposure. Exposures did also not differ regarding effects on time- and frequency-domain parameters of HRV. Similarly, blood leukocyte numbers, cell differentials and the blood levels of fibrinogen, C-reactive protein, antithrombin III, factor VIII, von Willebrand factor, ristocetin cofactor, sICAM-1, tumor necrosis factor alpha, interleukin 6, interleukin 8 and epithelial neutrophil activating peptide 78 were not altered by welding fume inhalation. However, there was a significant fall in the level of endothelin-1 (P < 0.01). In conclusion, the data did not indicate effects of clinical significance of a short-term high-level exposure to welding fumes on HRV or a set of blood hemostatic and acute inflammatory parameters in healthy subjects. The small but statistically significant effect on endothelin levels demonstrated that measurable effects could be elicited even in these individuals. Overall, welding fumes are not likely to exert acute cardiovascular effects in healthy individuals.

Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation.

PubMed

Mutlak, Haitham; Reyher, Christian; Meybohm, Patrick; Papadopoulos, Nestoras; Hanke, Alexander Alfons; Zacharowski, Kai; Weber, Christian Friedrich

2015-02-01

There have been many reports on how the usage of extracorporeal circulation (ECC) is independently associated with the induction of platelet dysfunctions. The aim of the present investigation was to study the capability of the multiple electrode aggregometry (MEA) using the Multiplate (Roche AG, Grenzach, Germany) device to reflect the extent of ECC-associated platelet dysfunctions. The study population consisted of patients who were treated with either hypothermic (cardiopulmonary bypass [CPB]) or normothermic (extracorporeal membrane oxygenation) ECC. Hemostatic analyses included conventional laboratory coagulation tests and aggregometric measures following stimulation with different agonists using MEA. The area under the aggregation curve in the ADPtest (ex vivo adenosine diphosphate induced platelet aggregation) of the MEA was defined as the primary end point. The analyses were performed before the usage of ECC (baseline) and 90 minutes (T1), 120 minutes (T2), 150 minutes (T3), and 180 minutes (T4) after the usage of ECC. In the hypothermic ECC group, additional hemostatic analyses were performed after the patient's postoperative admission to the intensive care unit (T5). Periprocedural data and results of other hemostatic testing were defined as secondary end points. A total of n = 40 patients were assessed for eligibility and n = 25 patients were finally enrolled into the study (hypothermic ECC group: n = 20; normothermic ECC group: n = 5). The extent of ADP-induced platelet aggregation decreased significantly between baseline and consecutive measuring points during hypothermic ECC and remained unchanged between T4 and T5. In the normothermic ECC group, ADP-induced aggregability was significantly lower at T1 compared with baseline and remained unchanged from T1 onward. Data from the present study indicate that ex vivo ADP-induced platelet aggregation in MEA reflects the time-dependent extent of ECC-induced platelet dysfunction. Georg Thieme Verlag KG Stuttgart · New York.

A novel hemostatic powder for upper gastrointestinal bleeding: a multicenter study (the "GRAPHE" registry).

PubMed

Haddara, Sami; Jacques, Jeremie; Lecleire, Stéphane; Branche, Julien; Leblanc, Sarah; Le Baleur, Yann; Privat, Jocelyn; Heyries, Laurent; Bichard, Philippe; Granval, Philippe; Chaput, Ulriikka; Koch, Stephane; Levy, Jonathan; Godart, Bruno; Charachon, Antoine; Bourgaux, Jean-François; Metivier-Cesbron, Elodie; Chabrun, Edouard; Quentin, Vincent; Perrot, Bastien; Vanbiervliet, Geoffroy; Coron, Emmanuel

2016-12-01

Background and study aims: The hemostatic powder TC-325 (Hemospray; Cook Medical, Winston-Salem, North Carolina, USA) has shown promising results in the treatment of upper gastrointestinal bleeding (UGIB) in expert centers in pilot studies. The aim of this study was to evaluate the feasibility and efficacy of TC-325 in a large prospective registry of use in routine practice. Patients and methods: The data of all patients treated with TC-325 were prospectively collected through a national registry. Outcomes were the immediate feasibility and efficacy of TC-325 application, as well as the rates of rebleeding at Day 8 and Day 30. Multivariate analysis was performed to determine predictive factors of rebleeding. Results: A total of 202 patients were enrolled and 64 endoscopists participated from 20 centers. TC-325 was used as salvage therapy in 108 patients (53.5 %). The etiology of bleeding was an ulcer in 75 patients (37.1 %), tumor in 61 (30.2 %), postendoscopic therapy in 35 (17.3 %), or other in 31 (15.3 %). Application of the hemostatic powder was found to be very easy or easy in 31.7 % and 55.4 %, respectively. The immediate efficacy rate was 96.5 %. Recurrence of UGIB was noted at Day 8 and Day 30 in 26.7 % and 33.5 %, respectively. Predictive factors of recurrence at Day 8 were melena at initial presentation and use of TC-325 as salvage therapy. Conclusion: These multicenter data confirmed the high rate of immediate hemostasis, excellent feasibility, and good safety profile of TC-325, which could become the treatment of choice in bleeding tumors or postendoscopic bleeding but not in bleeding ulcers where randomized studies are needed. ClinicalTrials.gov (NCT02595853). © Georg Thieme Verlag KG Stuttgart · New York.

Risk of Hemorrhage Attributed to Underlying Chronic Diseases and Uninterrupted Aspirin Therapy of Patients Undergoing Minor Oral Surgical Procedures: A Retrospective Cohort Study.

PubMed

Rojanaworarit, Chanapong; Limsawan, Soontaree

2017-01-01

This study aimed to estimate the risk of bleeding following minor oral surgical procedures and uninterrupted aspirin therapy in high-risk patients or patients with existing chronic diseases compared to patients who did not use aspirin during minor oral surgery at a public hospital. This retrospective cohort study analyzed the data of 2912 patients, aged 20 years or older, who underwent 5251 minor oral surgical procedures at a district hospital in Thailand. The aspirin group was comprised of patients continuing aspirin therapy during oral surgery. The non-aspirin group (reference) included all those who did not use aspirin during surgery. Immediate and late-onset bleeding was evaluated in each procedure. The risk ratio of bleeding was estimated using a multilevel Poisson regression. The overall cumulative incidence of immediate bleeding was 1.3% of total procedures. No late-onset bleeding was found. A significantly greater incidence of bleeding was found in the aspirin group (5.8% of procedures, p<0.001). After adjusting for covariates, a multilevel Poisson regression model estimated that the bleeding risk in the aspirin group was 4.5 times higher than that of the non-aspirin group (95% confidence interval, 2.0 to 10.0; p<0.001). However, all bleeding events were controlled by simple hemostatic measures. High-risk patients or patients with existing chronic diseases who continued aspirin therapy following minor oral surgery were at a higher risk of hemorrhage than general patients who had not used aspirin. Nonetheless, bleeding complications were not life-threatening and could be promptly managed by simple hemostatic measures. The procedures could therefore be provided with an awareness of increased bleeding risk, prepared hemostatic measures, and postoperative monitoring, without the need for discontinuing aspirin, which could lead to more serious complications.

Systemic and Topical Use of Tranexamic Acid in Spinal Surgery: A Systematic Review

PubMed Central

Winter, Sebastian F.; Santaguida, Carlo; Wong, Jean; Fehlings, Michael G.

2015-01-01

Study Design Combination of narrative and systematic literature reviews. Objectives Massive perioperative blood loss in complex spinal surgery often requires blood transfusions and can negatively affect patient outcome. Systemic use of the antifibrinolytic agent tranexamic acid (TXA) has become widely used in the management of surgical bleeding. We review the clinical evidence for the use of intravenous TXA as a hemostatic agent in spinal surgery and discuss the emerging role for its complementary use as a topical agent to reduce perioperative blood loss from the surgical site. Through a systematic review of published and ongoing investigations on topical TXA for spinal surgery, we wish to make spine practitioners aware of this option and to suggest opportunities for further investigation in the field. Methods A narrative review of systemic TXA in spinal surgery and topical TXA in surgery was conducted. Furthermore, a systematic search (using PRISMA guidelines) of PubMed (MEDLINE), EMBASE, and Cochrane CENTRAL databases as well as World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov (National Institutes of Health), and International Standard Randomized Controlled Trial Number registries was conducted to identify both published literature and ongoing clinical trials on topical TXA in spinal surgery. Results Of 1,631 preliminary search results, 2 published studies were included in the systematic review. Out of 285 ongoing clinical trials matching the search criteria, a total of 4 relevant studies were included and reviewed. Conclusion Intravenous TXA is established as an efficacious hemostatic agent in spinal surgery. Use of topical TXA in surgery suggests similar hemostatic efficacy and potentially improved safety as compared with intravenous TXA. For spinal surgery, the literature on topical TXA is sparse but promising, warranting further clinical investigation and consideration as a clinical option in cases with significant anticipated surgical site blood loss. PMID:27099820

A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-γ and IFN-λ) and Type 2 Inflammation (IL-5 and IL-13).

PubMed

Hansel, Trevor T; Tunstall, Tanushree; Trujillo-Torralbo, Maria-Belen; Shamji, Betty; Del-Rosario, Ajerico; Dhariwal, Jaideep; Kirk, Paul D W; Stumpf, Michael P H; Koopmann, Jens; Telcian, Aurica; Aniscenko, Julia; Gogsadze, Leila; Bakhsoliani, Eteri; Stanciu, Luminita; Bartlett, Nathan; Edwards, Michael; Walton, Ross; Mallia, Patrick; Hunt, Toby M; Hunt, Trevor L; Hunt, Duncan G; Westwick, John; Edwards, Matthew; Kon, Onn Min; Jackson, David J; Johnston, Sebastian L

2017-05-01

Rhinovirus infection is a major cause of asthma exacerbations. We studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations. We used nasosorption on days 0, 2-5 and 7 and bronchosorption at baseline and day 4 to sample mucosal lining fluid to investigate airway mucosal responses to rhinovirus infection in patients with allergic asthma (n=28) and healthy non-atopic controls (n=11), by using a synthetic absorptive matrix and measuring levels of 34 cytokines and chemokines using a sensitive multiplex assay. Following rhinovirus infection asthmatics developed more upper and lower respiratory symptoms and lower peak expiratory flows compared to controls (all P<0.05). Asthmatics also developed higher nasal lining fluid levels of an anti-viral pathway (including IFN-γ, IFN-λ/IL-29, CXCL11/ITAC, CXCL10/IP10 and IL-15) and a type 2 inflammatory pathway (IL-4, IL-5, IL-13, CCL17/TARC, CCL11/eotaxin, CCL26/eotaxin-3) (area under curve day 0-7, all P<0.05). Nasal IL-5 and IL-13 were higher in asthmatics at day 0 (P<0.01) and levels increased by days 3 and 4 (P<0.01). A hierarchical correlation matrix of 24 nasal lining fluid cytokine and chemokine levels over 7days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-γ, CXCL10/IP10, CXCL11/ITAC, IL-15 and IL-5 increased in bronchial lining fluid following viral infection (all P<0.05). Precision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis.

PubMed

Anzinger, Joshua J; Chang, Janet; Xu, Qing; Buono, Chiara; Li, Yifu; Leyva, Francisco J; Park, Bum-Chan; Greene, Lois E; Kruth, Howard S

2010-10-01

To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells.

3D Chirp Sonar Images on Fluid Migration Pathways and Their Implications on Seafloor Stability East of the Fangliao Submarine Canyon Offshore SW Taiwan

NASA Astrophysics Data System (ADS)

Lu, Y. W.; Liu, C. S.; Su, C. C.; Hsu, H. H.; Chen, Y. H.

2015-12-01

This study utilizes both chirp sonar images and coring results to investigate the unstable seafloor strata east of the Fangliao Submarine Canyon offshore southwestern Taiwan. We have constructed 3D chirp sonar images from a densely surveyed block to trace the attitude of an acoustic transparent layer and features caused by fluid activities. Based on the distribution of this transparent layer and fluid-related features, we suggest that this transparent layer forms a pathway for fluid migration which induces fluid-related characters such as acoustic blanking and fluid chimneys in the 3D chirp sonar images. Cored seafloor samples are used in this study to investigate the sediment compositions. The 210Pb activity profiles of the cores show oscillating and unsteady values at about 20~25 cm from core top. The bulk densities of the core samples in the same section (about 20~25 cm from core top) give values lower than those at deeper parts of the cores. These results indicate that the water content is much higher in the shallow sediments than in the deeper strata. From core sample analyses, we deduce that the local sediments are disturbed by liquefaction. From the analyses of 3D chirp sonar images and core data, we suggest that the seafloor east of the Fangliao Submarine Canyon is in an unstable condition, if disturbed by earthquakes, submarine landslides and gravity flows could be easily triggered and cause some geohazards, like breaking submarine cables during the 2006 Pingtung earthquake event.

Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer.

PubMed

Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

2013-05-01

Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer

PubMed Central

2013-01-01

Background Neurodegenerative diseases such as Alzheimer’s are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Methods Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30–180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Results Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Conclusion Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans. PMID:23635358

Yield-stress fluids foams: flow patterns and controlled production in T-junction and flow-focusing devices.

PubMed

Laborie, Benoit; Rouyer, Florence; Angelescu, Dan E; Lorenceau, Elise

2016-11-23

We study the formation of yield-stress fluid foams in millifluidic flow-focusing and T-junction devices. First, we provide a phase diagram for the unsteady operating regimes of bubble production when the gas pressure and the yield-stress fluid flow rate are imposed. Three regimes are identified: a co-flow of gas and yield-stress fluid, a transient production of bubble and a flow of yield-stress fluid only. Taking wall slip into account, we provide a model for the pressure at the onset of bubble formation. Then, we detail and compare two simple methods to ensure steady bubble production: regulation of the gas pressure or flow-rate. These techniques, which are easy to implement, thus open pathways for controlled production of dry yield-stress fluid foams as shown at the end of this article.

Identification of microRNAs and genes associated with hyperandrogenism in the follicular fluid of women with polycystic ovary syndrome.

PubMed

Xue, Yunping; Lv, Juan; Xu, Pengfei; Gu, Lin; Cao, Jian; Xu, Lingling; Xue, Kai; Li, Qian

2018-05-01

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which is characterized by hyperandrogenism (HA), chronic anovulation, polycystic ovaries, insulin resistance, and obesity. At present, the mechanism by which PCOS/HA occurs has not been fully elucidated, thus, the mechanisms behind and interventions for HA in PCOS are current hot topics in research. MiRNAs have recently been shown to serve as diagnostic or prognostic biomarkers in patients with cancer. Thus, we are currently focused on studying the altered expression of miRNAs in follicular fluid and their correlation with HA in PCOS. Illumina deep sequencing technology was used to explore different miRNAs in the follicular fluid of women with PCOS/HA and in the follicular fluid of women in a control group. Target prediction databases were then used to analyse the target genes of different expressed miRNAs, and GO analysis and the KEGG pathway database were used to identify the functions and the main biochemical and signalling pathways of differentially expressed target genes. The expression levels of 263 miRNAs were significantly different (>2-fold up-regulated or <0.5-fold down-regulated, P < 0.05) between the two groups of women. For example, the expression levels of miRNA (200a-3p, 10b-3p, 200b-3p, 29c-3p, 99a-3p, and 125a-5p) were significantly increased, while there was a decreased expression of miR-105-3p in PCOS patients with respect to the control. Literature has shown that the above seven miRNAs were associated with HA in PCOS. Furthermore, 31 770 genes were predicted to be targets of the 263 differentially expressed microRNAs. GO analysis and the KEGG pathway database showed involvement of these target genes in HA in PCOS. These results suggest the presence of differentially expressed miRNAs in the follicular fluid of women with PCOS/HA versus women in the control group. The potential role of these microRNAs was elucidated using bioinformatics tools and was found to be involved in the regulation of different pathways, biological functions, and cellular components underlying PCOS. The results of this research may reveal new mechanisms of PCOS/HA and suggest potential treatment targets. © 2017 Wiley Periodicals, Inc.

Fluid flow in deforming media: interpreting stable isotope signatures of marbles

NASA Astrophysics Data System (ADS)

Bond, C. E.

2016-12-01

Fluid flow in the crust is controlled by permeable networks. These networks can be created and destroyed dynamically during rock deformation. Rock deformation is therefore critical in controlling fluid pathways in the crust and hence the location of mineral and other resources. Here, evidence for deformation-enhanced fluid infiltration shows that a range of deformation mechanisms control fluid flow and chemical and isotopic equilibration. The results attest to localised fluid infiltration within a single metamorphic terrain (12km) over a range of metamorphic grades; ecologite- blueschist to greenschist. For fluid infiltrating marbles during ductile deformation, chemical and isotopic signatures are now homogenous; whilst fluid infiltration associated with brittle deformation results in chemical and isotopic heterogeneity at a microscale. The findings demonstrate how ductile deformation enhances equilibration of δ18O at a grain scale whilst brittle deformation does not. The control of deformation mechanisms in equilibrating isotopic and chemical heterogeneities have implications for the understanding of fluid-rock interaction in the crust. Interpretation of bulk stable isotope data, particularly in the use of isotope profiles to determine fluid fluxes into relatively impermeable units that have been deformed need to be used with care when trying to determine fluid fluxes and infiltration mechanisms.

A new glaucoma hypothesis: a role of glymphatic system dysfunction.

PubMed

Wostyn, Peter; Van Dam, Debby; Audenaert, Kurt; Killer, Hanspeter Esriel; De Deyn, Peter Paul; De Groot, Veva

2015-06-29

In a recent review article titled "A new look at cerebrospinal fluid circulation", Brinker et al. comprehensively described novel insights from molecular and cellular biology as well as neuroimaging research, which indicate that cerebrospinal fluid (CSF) physiology is much more complex than previously believed. The glymphatic system is a recently defined brain-wide paravascular pathway for CSF and interstitial fluid exchange that facilitates efficient clearance of interstitial solutes, including amyloid-β, from the brain. Although further studies are needed to substantiate the functional significance of the glymphatic concept, one implication is that glymphatic pathway dysfunction may contribute to the deficient amyloid-β clearance in Alzheimer's disease. In this paper, we review several lines of evidence suggesting that the glymphatic system may also have potential clinical relevance for the understanding of glaucoma. As a clinically acceptable MRI-based approach to evaluate glymphatic pathway function in humans has recently been developed, a unique opportunity now exists to investigate whether suppression of the glymphatic system contributes to the development of glaucoma. The observation of a dysfunctional glymphatic system in patients with glaucoma would provide support for the hypothesis recently proposed by our group that CSF circulatory dysfunction may play a contributory role in the pathogenesis of glaucomatous damage. This would suggest a new hypothesis for glaucoma, which, just like Alzheimer's disease, might be considered then as an imbalance between production and clearance of neurotoxins, including amyloid-β.

Tracking Hydrothermal Fluid Pathways from Surface Alteration Mineralogy: The Case of Licancura Geothermal Field, Northern Chile

NASA Astrophysics Data System (ADS)

Camus, E.; Elizalde, J. D.; Morata, D.; Wechsler, C.

2017-12-01

In geothermal systems alteration minerals are evidence of hot fluid flow, being present even in absence of other surface manifestations. Because these minerals result from the interaction between geothermal fluids and surrounding host rocks, they will provide information about features of thermal fluids as temperature, composition and pH, allowing tracking their changes and evolution. In this work, we study the Licancura Geothermal field located in the Andean Cordillera in Northern Chile. The combination of Principal Components Analysis on ASTER-L1T imagery and X Ray Diffraction (XRD) allow us to interpret fluid conditions and the areas where fluid flow took place. Results from red, green, blue color composite imagery show the presence of three types of secondary paragenesis. The first one corresponds to hematite and goethite, mainly at the east of the area, in the zone of eroded Pliocene volcanic edifices. The second one, mainly at the center of the area, highlighting propylitic alteration, includes minerals such as chlorite, illite, calcite, zeolites, and epidote. The third paragenesis, spatially related to the intersection between faults, represents advanced argillic alteration, includes minerals as alunite, kaolinite, and jarosite. XRD analysis support results from remote sensing techniques. These results suggest an acid pH hydrothermal fluid reaching temperatures at surface up to 80-100°C, which used faults as a conduit, originating advanced argillic minerals. The same fluid was, probably, responsible for propylitic paragenesis. However, iron oxides paragenesis identified in the area of eroded volcanoes probably corresponds to other processes associated with weathering rather than geothermal activity. In this work, we propose the applicability of remote sensing techniques as a first level exploration tool useful for high-altitude geothermal fields. Detailed clay mineral studies (XRD and SEM) would allow us to a better characterization of the geothermal fluid flow and the defining fluid pathways in the Licancura geothermal field. This work is a contribution to the FONDAP-CONICYT 15090013 Project. E.C. thanks CONICYT for her Ph.D. grant.

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

PubMed

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

2017-07-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

A simple technic for repeated collection of blood samples from mice.

PubMed

Stoltz, D R; Bendall, R D

1975-06-01

A device for repeated collection of small blood samples from mice was constructed from a plastic syringe. Blood was collected into a 3.33 lambda capillary tube. Bleeding was stopped by a hemostat made from a rubber stopper. This technic allows easy collection of approximately 20 serial samples within an 8-hr period.

Science, Technology and Requirements - Forum

DTIC Science & Technology

2012-10-18

Visable Absorbing and Electrostatically Adhesive Taggants •2008 Removal of CBRN Materials from Soil & Water using Nanosize Hydroxyapaptite •2009...Ribbon Composite for Optically Transparent Armor Windows •2010 UV Retroreflector Covert Taggants •2013 Proposed Warfighter Bandaging System Company... Bandaging System - Proposed Properties: •Bioactive fiber tissue scaffolding (bonds to both hard and soft tissue) •Hemostatic and Bioresorbable

Application of a Granular Mineral-Based Hemostatic Agent (QuikClot) to Reduce Blood Loss After Grade V Liver Injury in Swine

DTIC Science & Technology

2004-09-01

tion of tiletamine hydrochloride (HCl) and zolazepam HCl (Telazol, Fort Dodge Laboratories, Fort Dodge, IA), anesthe- sia was induced by mask using...Demceva M, Vournakis J, Finkielsztein S, Connolly RJ. Comparison of poly-N-acetyl glucosamine (P-GlcNAc) with absorbable collagen (Actifoam) and fibrin

Platelet aggregating material from equine arterial tissue

DOEpatents

Schneider, Morris D.

1983-02-22

Novel hemostatic agent comprises equine arterial fibrillar collagen in a carrier. The agent is useful for the aggregation of platelets for clinical diagnostic tests and for the clotting of blood, such as for controlling bleeding in warm blooded species. The fibrillar collagen is obtained by extracting homogenized equine arterial tissue with aqueous solutions followed by extensive dialysis.

Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality

DTIC Science & Technology

1994-10-27

paraformaidehyde in 500 mM Trehalose stored desiccated at RT, 4* C, or at -70,° C. Neither prep maintained good morphology at any temperature, and there...platelets, or para-platelets dried in Trehalose are as susceptible to loss of integrity over time as other preps. Our platelet handling techniques have

Out-of-Hospital Combat Casualty Care in the Current War in Iraq

DTIC Science & Technology

2009-02-01

could not be cleared with available suction equipment (3). There were 10 instances of chitosan hemostatic dressing use (3% of wounded in action). A...Eagle: MAJ David Mathias, MD, CPT Tommy Laird, MPAS, EMPA-C, CPT Scott G. Sullivan, MPAS, PA-C, and CPT Anthony Freiler, PA-C. We also express our

Fluids in crustal deformation: Fluid flow, fluid-rock interactions, rheology, melting and resources

NASA Astrophysics Data System (ADS)

Lacombe, Olivier; Rolland, Yann

2016-11-01

Fluids exert a first-order control on the structural, petrological and rheological evolution of the continental crust. Fluids interact with rocks from the earliest stages of sedimentation and diagenesis in basins until these rocks are deformed and/or buried and metamorphosed in orogens, then possibly exhumed. Fluid-rock interactions lead to the evolution of rock physical properties and rock strength. Fractures and faults are preferred pathways for fluids, and in turn physical and chemical interactions between fluid flow and tectonic structures, such as fault zones, strongly influence the mechanical behaviour of the crust at different space and time scales. Fluid (over)pressure is associated with a variety of geological phenomena, such as seismic cycle in various P-T conditions, hydrofracturing (including formation of sub-horizontal, bedding-parallel veins), fault (re)activation or gravitational sliding of rocks, among others. Fluid (over)pressure is a governing factor for the evolution of permeability and porosity of rocks and controls the generation, maturation and migration of economic fluids like hydrocarbons or ore forming hydrothermal fluids, and is therefore a key parameter in reservoir studies and basin modeling. Fluids may also help the crust partially melt, and in turn the resulting melt may dramatically change the rheology of the crust.

Fructose synthesis and transport at the uterine-placental interface of pigs: cell-specific localization of SLC2A5, SLC2A8, and components of the polyol pathway

USDA-ARS?s Scientific Manuscript database

The fetal fluids and uterine flushings of pigs contain higher concentrations of fructose than glucose, but fructose is not detected in maternal blood. Fructose can be synthesized from glucose via enzymes of the polyol pathway, aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD), transported ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buce, W.F.

Heretofore methods of preventing lost circulation in a formation zone during drilling operations, for example, involve pumping loss circulation material into the zone. These materials were wedged into the pores and indices of the formation with fluid pressure. In large pathways, these methods were often unsuccessful owing to the fact that the material could not be maintained at their desired location. By this method, a polymerizable material capable of forming hard, porous relatively insoluble popcorn polymers is placed in the formation zone desired to be sealed. The material is there maintained under polymerization conditions for a time sufficient to polymerizemore » in situ at least a portion of the material and restrict fluid pathways through the zone without exerting a force on the formation zone of a magnitude sufficient for fracturing it. (10 claims)« less

Selective Insulin-like Growth Factor Resistance Associated with Heart Hemorrhages and Poor Prognosis in a Novel Preclinical Model of the Hematopoietic Acute Radiation Syndrome.

PubMed

Kenchegowda, Doreswamy; Legesse, Betre; Hritzo, Bernadette; Olsen, Cara; Aghdam, Saeed; Kaur, Amandeep; Culp, William; Derrien-Colemyn, Alexandrine; Severson, Grant; Moroni, Maria

2018-05-29

Although bone marrow aplasia has been considered for the past decades as the major contributor of radiation-induced blood disorders, cytopenias alone are insufficient to explain differences in the prevalence of bleeding. In this study, the minipig was used as a novel preclinical model of hematopoietic acute radiation syndrome to assess if factors other than platelet counts correlated with bleeding and survival. We sought to determine whether radiation affected the insulin-like growth factor-1 (IGF-1) pathway, a growth hormone with cardiovascular and radioprotective features. Gottingen and Sinclair minipigs were exposed to ionizing radiation at hematopoietic doses. The smaller Gottingen minipig strain was more sensitive to radiation; differences in IGF-1 levels were minimal, suggesting that increased sensitivity could depend on weak response to the hormone. Radiation caused IGF-1 selective resistance by inhibiting the anti-inflammatory anti-oxidative stress IRS/PI3K/Akt but not the pro-inflammatory MAPK kinase pathway, shifting IGF-1 signaling towards a pro-oxidant, pro-inflammatory environment. Selective IGF-1 resistance associated with hemorrhages in the heart, poor prognosis, increase in C-reactive protein and NADPH oxidase 2, uncoupling of endothelial nitric oxide synthase, inhibition of nitric oxide (NO) synthesis and imbalance between the vasodilator NO and the vasoconstrictor endothelin-1 molecules. Selective IGF-1 resistance is a novel mechanism of radiation injury, associated with a vicious cycle amplifying reactive oxygen species-induced damage, inflammation and endothelial dysfunction. In the presence of thrombocytopenia, selective inhibition of IGF-1 cardioprotective function may contribute to the development of hemostatic disorders. This finding may be particularly relevant for individuals with low IGF-1 activity, such as the elderly or those with cardiometabolic dysfunctions.

Determinants of the Thrombogenic Potential of Multiwalled Carbon Nanotubes

PubMed Central

Burke, Andrew; Singh, Ravi; Carroll, David L.; Owen, John; Kock, Nancy D.; D’Agostino, Ralph; Torti, Frank M.; Torti, Suzy V.

2011-01-01

Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionalization of MWCNTs on thrombotic activity. In vitro, MWCNT activate the intrinsic pathway of coagulation as measured by activated partial thromboplastin time (aPTT) assays. Functionalization by amidation or carboxylation enhances this procoagulant activity. Mechanistic studies demonstrate that MWCNTs enhance propagation of the intrinsic pathway via a non-classical mechanism strongly dependent on factor IX. MWCNTs preferentially associate with factor IXa and may provide a platform for its activation. In addition to their effects on the coagulation cascade, MWCNTs activate platelets in vitro, with amidated MWCNTs exhibiting greater platelet activation than carboxylated or pristine MWCNTs. However, contrasting trends are obtained in vivo, where functionalization tends to diminish rather than enhance pro-coagulant activity. Thus, following systemic injection of MWCNTs in mice, pristine MWCNTs decreased platelet counts, increased vWF, and increased D-dimers. In contrast, carboxylated MWCNTS exhibited little procoagulant tendency in vivo, eliciting only a mild and transient decrease in platelets. Amidated MWCNTs elicited no statistically significant change in platelet count. Further, neither carboxylated nor amidated MWCNTs increased vWF or D-dimers in mouse plasma. We conclude that the pro-coagulant tendencies of MWCNTs observed in vitro are not necessarily recapitulated in vivo. Further, functionalization can markedly attenuate the procoagulant activity of MWCNTs in vivo. This work will inform the rational development of biocompatible MWCNTs for systemic delivery. PMID:21663954

Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice

PubMed Central

Shaw, Maureen A.; Kombrinck, Keith W.; McElhinney, Kathryn E.; Sweet, David R.; Flick, Matthew J.; Palumbo, Joseph S.; Cheng, Mei; Esmon, Naomi L.; Esmon, Charles T.; Brill, Alexander; Wagner, Denisa D.; Degen, Jay L.

2016-01-01

Thrombin-mediated proteolysis is central to hemostatic function but also plays a prominent role in multiple disease processes. The proteolytic conversion of fII to α-thrombin (fIIa) by the prothrombinase complex occurs through 2 parallel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermediate, meizothrombin (fIIaMZ). FIIaMZ has distinct catalytic properties relative to fIIa, including diminished fibrinogen cleavage and increased protein C activation. Thus, fII activation may differentially influence hemostasis and disease depending on the pathway of activation. To determine the in vivo physiologic and pathologic consequences of restricting thrombin generation to fIIaMZ, mutations were introduced into the endogenous fII gene, resulting in expression of prothrombin carrying 3 amino acid substitutions (R157A, R268A, and K281A) to limit activation events to yield only fIIaMZ. Homozygous fIIMZ mice are viable, express fII levels comparable with fIIWT mice, and have reproductive success. Although in vitro studies revealed delayed generation of fIIaMZ enzyme activity, platelet aggregation by fIIMZ is similar to fIIWT. Consistent with prior analyses of human fIIaMZ, significant prolongation of clotting times was observed for fIIMZ plasma. Adult fIIMZ animals displayed significantly compromised hemostasis in tail bleeding assays, but did not demonstrate overt bleeding. More notably, fIIMZ mice had 2 significant phenotypic advantages over fIIWT animals: protection from occlusive thrombosis after arterial injury and markedly diminished metastatic potential in a setting of experimental tumor metastasis to the lung. Thus, these novel animals will provide a valuable tool to assess the role of both fIIa and fIIaMZ in vivo. PMID:27252233

Starling forces drive intracranial water exchange during normal and pathological states.

PubMed

Linninger, Andreas A; Xu, Colin; Tangen, Kevin; Hartung, Grant

2017-12-31

To quantify the exchange of water between cerebral compartments, specifically blood, tissue, perivascular pathways, and cerebrospinal fluid-filled spaces, on the basis of experimental data and to propose a dynamic global model of water flux through the entire brain to elucidate functionally relevant fluid exchange phenomena. The mechanistic computer model to predict brain water shifts is discretized by cerebral compartments into nodes. Water and species flux is calculated between these nodes across a network of arcs driven by Hagen-Poiseuille flow (blood), Darcy flow (interstitial fluid transport), and Starling's Law (transmembrane fluid exchange). Compartment compliance is accounted for using a pressure-volume relationship to enforce the Monro-Kellie doctrine. This nonlinear system of differential equations is solved implicitly using MATLAB software. The model predictions of intraventricular osmotic injection caused a pressure rise from 10 to 22 mmHg, followed by a taper to 14 mmHg over 100 minutes. The computational results are compared to experimental data with R2=0.929. Moreover, simulated osmotic therapy of systemic (blood) injection reduced intracranial pressure from 25 to 10 mmHg. The modeled volume and intracranial pressure changes following cerebral edema agree with experimental trends observed in animal models with R2=0.997. The model successfully predicted time course and the efficacy of osmotic therapy for clearing cerebral edema. Furthermore, the mathematical model implicated the perivascular pathways as a possible conduit for water and solute exchange. This was a first step to quantify fluid exchange throughout the brain.

Cerebrospinal and Interstitial Fluid Transport via the Glymphatic Pathway Modeled by Optimal Mass Transport

PubMed Central

Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2017-01-01

The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4 min over ∼3 hrs in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins. PMID:28323163

Cerebrospinal and interstitial fluid transport via the glymphatic pathway modeled by optimal mass transport.

PubMed

Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2017-05-15

The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4min over ∼3h in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins. Copyright © 2017. Published by Elsevier Inc.

Sperm release pathway

MedlinePlus Videos and Cool Tools

... organs include the testes, epididymis, urethra, vas deferens, prostate gland, seminal vesicle, and penis. The testes are ... ducts toward the urethra, passing first by the prostate gland, where a milky fluid is added to ...

Near-Surface Transport Pathways in the North Atlantic Ocean: Looking for Throughput from the Subtropical to the Subpolar Gyre

NASA Astrophysics Data System (ADS)

Rypina, I. I.; Pratt, L. J.; Lozier, M.

2011-12-01

Motivated by discrepancies between Eulerian transport estimates and the behavior of Lagrangian surface drifters, near-surface transport pathways and processes in the North Atlantic are studied using a combination of data, altimetric surface heights, statistical analysis of trajectories, and dynamical systems techniques. Particular attention is paid to the issue of the subtropical-to-subpolar intergyre fluid exchange. The velocity field used in this study is composed of a steady drifter-derived background flow, upon which a time-dependent altimeter-based perturbation is superimposed. This analysis suggests that most of the fluid entering the subpolar gyre from the subtropical gyre within two years comes from a narrow region lying inshore of the Gulf Stream core, whereas fluid on the offshore side of the Gulf Stream is largely prevented from doing so by the Gulf Stream core, which acts as a strong transport barrier, in agreement with past studies. The transport barrier near the Gulf Stream core is robust and persistent from 1992 until 2008. The qualitative behavior is found to be largely independent of the Ekman drift.

Changes in hemostasis caused by different replacement fluids and outcome in therapeutic plasma exchange in pediatric patients in a retrospective single center study.

PubMed

Witt, Volker; Pichler, Herbert; Beiglboeck, Elisabeth; Kursten, Friedrich; Weidner, Lisa

2017-02-01

Therapeutic plasma exchange (TPE) is a generally accepted and frequently performed procedure for numerous therapeutic indications in adults. Slowly, TPE is also becoming more and more popular in the treatment of pediatric patients. Although, we know that TPE is safe in pediatric patients, the outcome of children treated with TPE is rarely reported. Furthermore, there are only general recommendations regarding the plasma replacement fluid for children and these are adopted from adults. Data concerning outcome and the influence of different types of replacement fluids on hemostasis in children are scarce. We retrospectively evaluated 324 TPE treatments performed in 35 patients between 2008 and 2013 in our level 4 institution for pediatric hematology and oncology. The plasmapheresis procedures were categorized into three groups based on the replacement fluid used. The first group received solvent/detergent-treated (S/D) plasma (70.0% of patients), the second group was administered 5% human albumin (7.7% of patients) and the third group was treated with a combination of human albumin 5% and S/D plasma (22.3% of patients). To assess hemostasis, data on INR, aPTT, fibrinogen and ATIII were collected before and after plasmapheresis from the patients' charts. A modified Multi Organ Dysfunction Syndrome (MODS) Index was used to classify organ failure. Patient outcome, survival rate and adverse events were evaluated. We found a significant increase in the INR by 35.83% and of the aPTT by 18.53% within the human albumin group. The INR and aPTT of patients allocated to the S/D plasma group decreased by 1.58% and 15.77% on average, respectively. The combination group revealed a mild increase of the INR (9.47%), accompanied by a reduction of aPTT (5.97%). Furthermore we found that the survival rate was significantly associated with a MODS Index of <2 (p<0.001). Overall, the number of adverse events was low (1.2%) and none of these were considered life-threatening. Hemostasis could be preserved in a clinically acceptable range for a variety of underlying diseases with SD plasma alone or in combination with human albumin. Based on our results we would recommend practitioners to closely pre-estimate the hemostatic situation before using human albumin alone in critically ill pediatric patients with a limited ability to produce coagulation factors. The outcome of the patients in our collective exprience is correlated to the extent of organ dysfunction. Therefore further controlled studies are highly recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reactive oxygen species: players in the cardiovascular effects of testosterone

PubMed Central

Carneiro, Fernando S.; Carvalho, Maria Helena C.; Reckelhoff, Jane F.

2015-01-01

Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID:26538238

Calycophyllum spruceanum (Benth.), the Amazonian "Tree of Youth" Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans.

PubMed

Peixoto, Herbenya; Roxo, Mariana; Koolen, Hector; da Silva, Felipe; Silva, Emerson; Braun, Markus Santhosh; Wang, Xiaojuan; Wink, Michael

2018-02-27

The tree popularly known in Brazil as mulateiro or pau-mulato ( Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum . To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry)/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans . The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the "tree of youth", however more studies are needed to clarify its putative benefits to human health.

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

PubMed Central

Beaulieu, Lea M.; Church, Frank C.

2014-01-01

Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1–50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified “checkerboard” analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1. PMID:17254565

Use of the holmium:YAG laser in urology.

PubMed

Johnson, D E; Cromeens, D M; Price, R E

1992-01-01

The tissue effects of a holmium:YAG (Ho:YAG) laser operating at a wavelength of 2.1 mu with a maximum power of 15 watts (W) and 10 different energy-pulse settings was systematically evaluated on kidney, bladder, prostate, ureteral, and vasal tissue in the dog. In addition, various urologic surgical procedures (partial nephrectomy, transurethral laser incision of the prostate, and laser-assisted vasovasostomy) were performed in the dog, and a laparoscopic pelvic lymph node dissection was carried out in a pig. Although the Ho:YAG laser has a strong affinity for water, precise tissue ablation was achieved in both the contact and non-contact mode when used endoscopically in a fluid medium to ablate prostatic and vesical tissue. Using the usual parameters for tissue destruction (blanching without charring), the depth of thermal injury in the bladder and ureter was kept superficial. In performing partial nephrectomies, a 2-fold reduction in the zone of coagulative necrosis was demonstrated compared to the use of the continuous wave Neodymium:YAG laser (Nd:YAG). When used through the laparoscope, the Ho:YAG laser provided precise cutting and, combined with electrocautery, allowed the dissection to proceed quickly and smoothly. Hemostatic control was adequate in all surgical procedures. Although the results of these investigations are preliminary, our initial experience with the Ho:YAG laser has been favorable and warrants further investigations.

Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients.

PubMed

Koskinen, Anna; Vuolteenaho, Katriina; Nieminen, Riina; Moilanen, Teemu; Moilanen, Eeva

2011-01-01

In the present study, we investigated the role of adipocytokine leptin in the pathogenesis of osteoarthritis (OA) by measuring its effects on matrix metalloproteinase (MMP) production in human OA cartilage. In addition, the correlations between leptin and MMP concentrations in synovial fluid from OA patients were studied. Cartilage tissue obtained from leftover pieces of total knee replacement surgery from patients with OA was used in the experiments. Production of collagenases MMP-1, MMP-8 and MMP-13, and stromelysin-1 (MMP-3) in the cartilage was measured by immunoassay and the signalling pathways were explored by pharmacological means. In addition, synovial fluid samples were collected from 84 OA patients undergoing knee replacement surgery. The concentrations of leptin and MMPs in synovial fluid were measured by immunoassay. Leptin alone and in combination with IL-1β enhanced production of MMP-1, MMP-3, and MMP-13 in human OA cartilage, while MMP-8 concentrations remained undetectable. The effects of leptin on MMP-1, MMP-3 and MMP-13 production were mediated through transcription factor NF-κβ, and through protein kinase C and MAP kinase pathways. Interestingly, leptin concentrations in synovial fluid from OA patients correlated positively with MMP-3 (r=0.51, p<0.001) and MMP-1 (r=0.41, p<0.001) levels. To our knowledge, this is the first study to show that leptin up-regulates MMP-1 and MMP-3 production in human OA cartilage and correlates positively to MMP-1 and MMP-3 in synovial fluid from OA patients. The findings suggest that leptin has catabolic effects in OA joints by increasing MMP production in cartilage.

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury.

PubMed

Peters, Dorothea M; Vadász, István; Wujak, Lukasz; Wygrecka, Malgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E

2014-01-21

TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which--together with patch-clamp and flow cytometry studies--identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys(43). Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β-dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs.

Jak/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2012-07-01

display different cellular responses n status epilepticus models (Schauwecker and Steward, 1997), nd/or are often used in transgenic studies. Severe brain...after status epilepticus (SE). This study investigated changes in these pathways after experimental TBI in the rat using a lateral fluid percussion... status epilepticus (SE) (Choi et al., 2003, Lund et al., 2008). Following SE, the JaK/STAT pathway has been shown to regulate the γ-aminobutyric acid

Resuscitation and Transfusion Principles for Traumatic Hemorrhagic Shock

DTIC Science & Technology

2009-11-01

hyperfibrinolysis. We also describe the concept of damage control resuscitation (DCR), an early and aggressive prevention and treatment of hemorrhagic shock... prevention and treatment of acidosis, hypothermia, and hypocalcemia, avoidance of hemodilution, and hemostatic resuscitation with transfusion of red...are potentially preventable and 66–80% of these deaths occur from hemorrhage.3,4 Rural civilian data indicate that approximately 10% of traumatic

Label-Free LC-MS/MS Proteomic Analysis of Cerebrospinal Fluid Identifies Protein/Pathway Alterations and Candidate Biomarkers for Amyotrophic Lateral Sclerosis.

PubMed

Collins, Mahlon A; An, Jiyan; Hood, Brian L; Conrads, Thomas P; Bowser, Robert P

2015-11-06

Analysis of the cerebrospinal fluid (CSF) proteome has proven valuable to the study of neurodegenerative disorders. To identify new protein/pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis (ALS), we performed comparative proteomic profiling of CSF from sporadic ALS (sALS), healthy control (HC), and other neurological disease (OND) subjects using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1712 CSF proteins were detected and relatively quantified by spectral counting. Levels of several proteins with diverse biological functions were significantly altered in sALS samples. Enrichment analysis was used to link these alterations to biological pathways, which were predominantly related to inflammation, neuronal activity, and extracellular matrix regulation. We then used our CSF proteomic profiles to create a support vector machines classifier capable of discriminating training set ALS from non-ALS (HC and OND) samples. Four classifier proteins, WD repeat-containing protein 63, amyloid-like protein 1, SPARC-like protein 1, and cell adhesion molecule 3, were identified by feature selection and externally validated. The resultant classifier distinguished ALS from non-ALS samples with 83% sensitivity and 100% specificity in an independent test set. Collectively, our results illustrate the utility of CSF proteomic profiling for identifying ALS protein/pathway alterations and candidate disease biomarkers.

Disorder of Endothelia Vessels' Functional State with Malignant Tumors in Patients Exposed Anthropogenic Radiation.

PubMed

Pak, Laura; Noso, Yoshihiro; Chaizhunusova, Nailya; Anambaeva, Zukhra; Adylkhanov, Tasbolat; Takeichi, Nobuo; Lzhaev, Sayakhat; Aldyngurov, Daniyar; Tuleutayeva, Raikhan; Argynbekova, Ainur; Tanysheva, Gulyash; Zhazykbayeva, Lashyn; Baissalbayeva, Ainur; Rakhypbekov, Tolebay

2016-01-01

The aim of this research is to determine the characteristics of endothelial factors and the hemostatic system conditions with malignant neoplasms patients, which were exposed to ionizing radiation. Total number of examined people is 223, 153 of them are patients with gastrointestinal tract oncopathology. The article presents the results of the analysis of numerical indicators of endothelial condition and platelet hemostasis of patients, who had cancer. They lived in the regions of Kazakhstan, subjected to contamination of radionuclides as a result of nuclear weapons tests, which took place in this region from 1949 to 1989. These results then were compared to cancer patients and healthy individuals with no radiation risk. The study revealed the presence of higher levels of endothelial dysfunction and following trigger of the hemostatic system in patients with malignant tumors of the gastrointestinal tract. In particular, the defined high degree of endothelial dysfunction include endothelium- dependent vasodilation, content desquamated endothelial cells in peripheral blood and von Willebrand factor. These indicators have a clear correlation with the degree of disorder of studied parameters of the hemostasis, which can cause the development of thrombotic complications.

Aortic occlusion balloon catheter technique is useful for uncontrollable massive intraabdominal bleeding after hepato-pancreato-biliary surgery.

PubMed

Miura, Fumihiko; Takada, Tadahiro; Ochiai, Takenori; Asano, Takehide; Kenmochi, Takashi; Amano, Hodaka; Yoshida, Masahiro

2006-04-01

Massive intraabdominal hemorrhage sometimes requires urgent hemostatic surgical intervention. In such cases, its rapid stabilization is crucial to reestablish a general hemodynamic status. We used an aortic occlusion balloon catheter in patients with massive intraabdominal hemorrhage occurring after hepato-pancreato-biliary surgery. An 8-French balloon catheter was percutaneously inserted into the aorta from the femoral artery, and the balloon was placed just above the celiac artery. Fifteen minutes inflation and 5 minutes deflation were alternated during surgery until the bleeding was surgically controlled. An aortic occlusion balloon catheter was inserted on 13 occasions in 10 patients undergoing laparotomy for hemostasis of massive hemorrhage. The aorta was successfully occluded on 12 occasions in nine patients. Both systolic pressure and heart rate were normalized during aortic occlusion, and the operative field became clearly visible after adequate suction of leaked blood. Bleeding sites were then easily found and controlled. Hemorrhage was successfully controlled in 7 of 10 patients (70%), and they were discharged in good condition. The aortic occlusion balloon catheter technique was effective for easily controlling massive intraabdominal bleeding by hemostatic procedure after hepato-pancreato-biliary surgery.

Advanced drug delivery systems for antithrombotic agents

PubMed Central

Greineder, Colin F.; Howard, Melissa D.; Carnemolla, Ronald; Cines, Douglas B.

2013-01-01

Despite continued achievements in antithrombotic pharmacotherapy, difficulties remain in managing patients at high risk for both thrombosis and hemorrhage. Utility of antithrombotic agents (ATAs) in these settings is restricted by inadequate pharmacokinetics and narrow therapeutic indices. Use of advanced drug delivery systems (ADDSs) may help to circumvent these problems. Various nanocarriers, affinity ligands, and polymer coatings provide ADDSs that have the potential to help optimize ATA pharmacokinetics, target drug delivery to sites of thrombosis, and sense pathologic changes in the vascular microenvironment, such as altered hemodynamic forces, expression of inflammatory markers, and structural differences between mature hemostatic and growing pathological clots. Delivery of ATAs using biomimetic synthetic carriers, host blood cells, and recombinant fusion proteins that are activated preferentially at sites of thrombus development has shown promising outcomes in preclinical models. Further development and translation of ADDSs that spare hemostatic fibrin clots hold promise for extending the utility of ATAs in the management of acute thrombotic disorders through rapid, transient, and targeted thromboprophylaxis. If the potential benefit of this technology is to be realized, a systematic and concerted effort is required to develop clinical trials and translate the use of ADDSs to the clinical arena. PMID:23798715

Adhesion of Blood Clots Can Be Enhanced When Copolymerized with a Macromer That Is Crosslinked by Coagulation Factor XIIIa.

PubMed

Chan, Karen Y T; Zhao, Chunyi; Siren, Erika M J; Chan, Jeanne C Y; Boschman, Jeffrey; Kastrup, Christian J

2016-06-13

The adhesion of blood clots to blood vessels, such as through the adhesion of fibrin, is essential in hemostasis. While numerous strategies for initiating clot formation and preventing clot lysis are being developed to create improved hemostatic agents, strategies for enhancing clot adhesion have not been widely explored. Here, we show that adhesion of blood clots can be increased by adding a previously characterized synthetic polymer that is crosslinked by coagulation factor XIIIa during clotting. Addition of the polymer to normal plasma increased the adhesive strength of clots by 2-fold. It also recovered the adhesive strength of nonadhesive fibrinogen-deficient whole blood clots from <0.06 kPa to 1.9 ± 0.14 kPa, which is similar to the adhesive strength of a fibrinogen-rich clot (1.8 ± 0.64 kPa). The polymer also enabled plasma clots to remain adhered under fibrinolytic conditions. By demonstrating that the adhesive strength of clots can be increased with a synthetic material, this provides a potential strategy for creating advanced hemostatic materials, such as treatments for fibrinogen deficiency in trauma-induced coagulopathy.

The hemostatic efficacy of chitosan-pads in hemodialysis patients with significant bleeding tendency.

PubMed

Misgav, Mudi; Lubetszki, Ahron; Brutman-Barazani, Tami; Martinowitz, Uri; Kenet, Gili

2017-05-15

Patients on chronic hemodialysis often have acquired coagulopathy that can aggravate bleeding from puncture site after needle extraction. Chitosan-based pads have been reported to accelerate hemostasis even in the presence of coagulopathy. The aim of this study was to evaluate the hemostatic efficacy of the chitosan pads compared to gauze pads, applied for local hemostasis. A crossover study in a cohort of patients on hemodialysis with extended time to hemostasis after needle extraction. At the end of each dialysis, either gauze or chitosan pad was applied on both access points (arterial and venous). The type of pad was changed in the next dialysis all together 5 times in each patient (10 applications per patient for every pad). A total of 288 applications, 144 for each type of pad, were performed in 15 patients. The average time to hemostasis for the entire group was significantly shorter with the chitosan pads compared to the regular gauze pads ("arterial" point 3 vs. 18.5 min, p<0.001 "venous" access 2.8 vs. 13.2 min, p<0.001, respectively). Chitosan pads significantly reduce time to hemostasis and should be considered for the treatment of accessible bleeds in patients with coagulopathy.

Chitosan-based dressing for the treatment of external/accessible bleedings in children with bleeding tendency.

PubMed

Misgav, Mudi; Kenet, Gili; Martinowitz, Uriel

2014-03-01

Bleeding episodes in patients with congenital or acquired bleeding disorders are usually managed with factor concentrates or blood products. However, external and accessible bleeds may effectively be managed with topical hemostasis. After the application of the Hemcon, a Food and Drug Administration-approved chitosan-based hemostatic dressing was used as the "last resort" to successfully control external bleeds in 2 patients with severe bleeding disorders. We describe a single-center experience with this dressing, including its use in pediatric patients as the first mode of therapy. A total of 5 patients (median age 2 y) with severe bleeding disorders were treated with topical chitosan-based dressing for a total of 6 bleeding episodes. The dressing was used either after the failure of extensive systemic therapy or as the first choice of treatment. In 4 of the 6 episodes, bleeding ceased immediately alleviating the need for systemic therapy. There was no rebleeding after the removal of the dressing and no adverse events or local skin reactions were recorded. Hemostatic dressings, such as the chitosan, should be encouraged for the treatment of external/accessible bleeds, especially among the pediatric patients with bleeding tendency.

Liver damage induced in rats by malathion impurities.

PubMed

Keadtisuke, S; Dheranetra, W; Nakatsugawa, T; Fukuto, T R

1990-06-01

Administration of a single oral dose of the malathion impurity, O,O,S-trimethyl phosphorothioate (OOS-Me) or O,S,S-trimethyl phosphorodithioate (OSS-Me), to the rat resulted in hemostatic disorders, e.g. prolongation of blood clotting, prothrombin and thrombin time. Deficiency of coagulation Factors II, V and VII was also observed. OOS-Me and OSS-Me also caused dose-dependent increases of beta-glucuronidase in the blood with a maximum of 15- and 31-fold observed following treatment with 60 mg/kg OOS-Me and 40 mg/kg OSS-Me, respectively. Analysis of serum beta-glucuronidase by isoelectrofocusing electrophoresis showed that the liver endoplasmic reticulum was the source of this enzyme released into the blood. Co-treatment of OOS-Me with 5% O,O,O-trimethyl phosphorothioate (OOO-Me), a potent antagonist of OOS-Me-induced delayed toxicity, prevented hemostatic disorders but had no effect in reducing beta-glucuronidase levels. However, pretreatment of rats with piperonyl butoxide reduced the amount of beta-glucuronidase released into the blood. Of other O,O,S-trialkyl phosphorothioates examined, the O,O-diethyl S-alkyl phosphorothioates showed the highest activity in increasing beta-glucuronidase levels.

Bone wax in Neurosurgery: A Review.

PubMed

Das, Joe M

2018-05-09

In this occasion of 125 years after the so-called "initial" use of bone wax (BW) by Sir Victor Horsley, a review of this age-old hemostatic agent deemed appropriate. The first use of BW for hemostasis is dated back to the 18 th century when modeling or candle wax was used for hemostasis. Though the pioneers in the usage of BW in craniofacial surgeries were Belloq, Professor Khristian Khristianovich Salomon and François Magendie, its first successful use in neurosurgery was demonstrated by Henri Ferdinand Dolbeau in 1864, following the extirpation of a frontal osteoma. This was further popularized by Sir Victor Alexander Haden Horsley, the father of British neurosurgery, who is often incorrectly mentioned as the inventor of BW. Originally derived from bees' wax, the currently available commercial preparation contains paraffin wax and Isopropyl palmitate in addition. The main action being mechanical tamponade, BW has found several other uses in neurosurgery, other than being a hemostatic agent. Though it is cost-effective, the use of BW is associated with several complications also, including ineffective bone healing and infection. So several other alternatives are coming up, but none has yet been able to fully replace "Horsley's wax" till date. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization of a microbial polysaccharide-based bioflocculant and its anti-inflammatory and pro-coagulant activity.

PubMed

Zhong, Chunying; Cao, Gang; Rong, Kuan; Xia, Zhengwu; Peng, Ting; Chen, Honggao; Zhou, Jiangang

2018-01-01

We describe a novel bioflocculant, MBF-15, which is an exopolysaccharide extracted from the alkaliphilic bacterium Paenibacillus jamilae. The biophysical characteristics of MBF-15 were determined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. MBF-15 was also evaluated for its biocompatibility by examining its inflammatory, coagulant, and hemostatic properties in vitro and in vivo. Pretreatment of peripheral blood mononuclear cells with MBF-15 inhibited lipopolysaccharide-stimulated expression of inducible nitric oxide synthase, production of nitric oxide, and secretion of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, MBF-15 increased both mRNA and protein levels of the anti-inflammatory cytokines transforming growth factor-β and IL-10. The hemocompatibility of MBF-15 was investigated by measuring the hemolysis ratio and clotting times. MBF-15 had high pro-thrombogenic activity but was not hemolytic. In a rat model, MBF-15 showed superior hemostatic properties compared with chitosan. Thus, MBF-15 offers a promising combination of anti-inflammatory and pro-coagulant properties that may be useful for hemostasis in a variety of clinical settings. Copyright © 2017 Elsevier B.V. All rights reserved.

Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

PubMed

Vonk, Alexander B; Muntajit, Warayouth; Bhagirath, Pranav; van Barneveld, Laurentius J; Romijn, Johannes W; de Vroege, Roel; Boer, Christa

2012-10-01

The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P < 0.01]. Cell salvage resulted in the lowest hemolysis levels in the transfusion bag. Retransfusion of cell saver blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

PubMed

Levy, Jerrold H; Grottke, Oliver; Fries, Dietmar; Kozek-Langenecker, Sibylle

2017-04-01

Plasma products, including fresh frozen plasma, are administered extensively in a variety of settings from massive transfusion to vitamin K antagonist reversal. Despite the widespread use of plasma as a hemostatic agent in bleeding patients, its effect in comparison with other available choices of hemostatic therapies is unclear. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed Central, and databases of ongoing trials for randomized controlled trials that assessed the efficacy and/or safety of therapeutic plasma as an intervention to treat bleeding patients compared with other interventions or placebo. Of 1243 unique publications retrieved in our initial search, no randomized controlled trials were identified. Four nonrandomized studies described the effect of therapeutic plasma in bleeding patients; however, data gathered from these studies did not allow for comparison with other therapeutic interventions primarily as a result of the low number of patients and the use of different (or lack of) comparators. We identified two ongoing trials investigating the efficacy and safety of therapeutic plasma, respectively; however, no data have been released as yet. Although plasma is used extensively in the treatment of bleeding patients, evidence from randomized controlled trials comparing its effect with those of other therapeutic interventions is currently lacking.

Plasma Sheet Circulation Pathways

NASA Technical Reports Server (NTRS)

Moore, Thomas E.; Delcourt, D. C.; Slinker, S. P.; Fedder, J. A.; Damiano, P.; Lotko, W.

2008-01-01

Global simulations of Earth's magnetosphere in the solar wind compute the pathways of plasma circulation through the plasma sheet. We address the pathways that supply and drain the plasma sheet, by coupling single fluid simulations with Global Ion Kinetic simulations of the outer magnetosphere and the Comprehensive Ring Current Model of the inner magnetosphere, including plasmaspheric plasmas. We find that the plasma sheet is supplied with solar wind plasmas via the magnetospheric flanks, and that this supply is most effective for northward IMF. For southward IMF, the innermost plasma sheet and ring current region are directly supplied from the flanks, with an asymmetry of single particle entry favoring the dawn flank. The central plasma sheet (near midnight) is supplied, as expected, from the lobes and polar cusps, but the near-Earth supply consists mainly of slowly moving ionospheric outflows for typical conditions. Work with the recently developed multi-fluid LFM simulation shows transport via plasma "fingers" extending Earthward from the flanks, suggestive of an interchange instability. We investigate this with solar wind ion trajectories, seeking to understand the fingering mechanisms and effects on transport rates.

Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway

PubMed Central

Sethi, Sanjeev; Gamez, Jeffrey D.; Vrana, Julie A.; Theis, Jason D.; Bergen, H. Robert; Zipfel, Peter F.; Dogan, Ahmet; Smith, Richard J. H.

2009-01-01

Dense Deposit Disease (DDD), or membranoproliferative glomerulonephritis type II, is a rare renal disease characterized by dense deposits in the mesangium and along the glomerular basement membranes that can be seen by electron microscopy. Although these deposits contain complement factor C3, as determined by immunofluorescence microscopy, their precise composition remains unknown. To address this question, we used mass spectrometry to identify the proteins in laser microdissected glomeruli isolated from paraffin-embedded tissue of eight confirmed cases of DDD. Compared to glomeruli from five control patients, we found that all of the glomeruli from patients with DDD contain components of the alternative pathway and terminal complement complex. Factor C9 was uniformly present as well as the two fluid-phase regulators of terminal complement complex clusterin and vitronectin. In contrast, in nine patients with immune complex–mediated membranoproliferative glomerulonephritis, glomerular samples contained mainly immunoglobulins and complement factors C3 and C4. Our study shows that in addition to fluid-phase dysregulation of the alternative pathway, soluble components of the terminal complement complex contribute to glomerular lesions found in DDD. PMID:19177158

Porosity developed during mineral replacement reactions: implications for fluid flux in the Earth

NASA Astrophysics Data System (ADS)

Putnis, Christine V.; Trindade Pedrosa, Elisabete; Hövelmann, Jörn; Renard, François; Ruiz-Agudo, Encarnacion

2017-04-01

Aqueous fluids, that are ubiquitous in the crust of the Earth, will move through possible pathways in rocks. Rocks characteristically have low permeability but fractures can provide fast fluid channels. Mineral grain boundaries also present easy fluid pathways. However, porosity within minerals forms when a mineral is out of equilibrium with an aqueous fluid and reactions take place in an attempt to reach a new equilibrium. Commonly, dissolution at a mineral-fluid interface initiates one or several coupled reactions involving dissolution and precipitation (Putnis C.V. and Ruiz-Agudo E., 2013; Ruiz-Agudo et al., 2014). In pseudomorphic volume-deficit reactions, a new phase forms while porosity is created, and thereby reactive fluid flow through the originally solid mineral is enhanced. These coupled dissolution-replacement reactions therefore will constrain the flux of material carried by the fluid. These reactions are common during such processes as metamorphism, metasomatism, and weathering. When rock-forming minerals such as feldspars, olivine, pyroxenes and carbonates are in contact with aqueous fluids (typically NaCl-rich) porosity is formed during the interfacial replacement reactions. Elements present in the parent mineral are released to the fluid and therefore mobilized for transport elsewhere. Porosity formation has been shown in a number of systems, such as during the albitisation of feldspars (Hövelmann et al., 2009) and the replacement of carbonates by apatite phases (Pedrosa et al., 2016). Some of these examples will be presented as well as examples from atomic force microscopy (AFM) experiments used to image these reactions at a nanoscale, especially at the calcite-fluid interface, when new phases can be directly observed forming. This mechanism has also been shown as a means of carbon and phosphorus sequestration and for the removal of toxic elements from superficial waters, such as Se and As. References Ruiz-Agudo E., Putnis C.V., Putnis A. (2014) Coupled dissolution and precipitation at mineral-fluid interfaces. Chem. Geol., 383, 132-146. Putnis C.V. and Ruiz-Agudo E. (2013) The mineral-water interface: where minerals react with the environment. Elements, 9, 177-182. Hövelmann J., Putnis A., Geisler T., Schmidt B.C., Golla-Schindler U. (2009) The replacement of plagioclase feldspars by albite: observations from hydrothermal experiments. Contrib. Min. and Pet. 159, 43-59. Pedrosa E.T., Putnis C.V., Putnis A. (2016) The pseudomorphic replacement of marble by apatite: the role of fluid composition. Chem. Geol., 425, 1-11.

Well Completion Methods for Aquifer Protection

EPA Pesticide Factsheets

This presentation outlines how appropriate due diligence can be undertaken concurrent with leasing, site acquisition, permitting and development of prospect areas to identify and mitigate potential pathways of frac fluids other than intended target zones.

Organic intermediates in the anaerobic biodegradation of coal to methane under laboratory conditions

USGS Publications Warehouse

Orem, William H.; Voytek, Mary A.; Jones, Elizabeth J.; Lerch, Harry E.; Bates, Anne L.; Corum, Margo D.; Warwick, Peter D.; Clark, Arthur C.

2010-01-01

Organic intermediates in coal fluids produced by anaerobic biodegradation of geopolymers in coal play a key role in the production of methane in natural gas reservoirs. Laboratory biodegradation experiments on sub-bituminous coal from Texas, USA, were conducted using bioreactors to examine the organic intermediates relevant to methane production. Production of methane in the bioreactors was linked to acetate accumulation in bioreactor fluid. Long chain fatty acids, alkanes (C19–C36) and various low molecular weight aromatics, including phenols, also accumulated in the bioreactor fluid and appear to be the primary intermediates in the biodegradation pathway from coal-derived geopolymers to acetate and methane.

Cascadia subduction tremor muted by crustal faults

USGS Publications Warehouse

Wells, Ray; Blakely, Richard J.; Wech, Aaron G.; McCrory, Patricia A.; Michael, Andrew

2017-01-01

Deep, episodic slow slip on the Cascadia subduction megathrust of western North America is accompanied by low-frequency tremor in a zone of high fluid pressure between 30 and 40 km depth. Tremor density (tremor epicenters per square kilometer) varies along strike, and lower tremor density statistically correlates with upper plate faults that accommodate northward motion and rotation of forearc blocks. Upper plate earthquakes occur to 35 km depth beneath the faults. We suggest that the faults extend to the overpressured megathrust, where they provide fracture pathways for fluid escape into the upper plate. This locally reduces megathrust fluid pressure and tremor occurrence beneath the faults. Damping of tremor and related slow slip caused by fluid escape could affect fault properties of the megathrust, possibly influencing the behavior of great earthquakes.

Failure of cap-rock seals as determined from mechanical stratigraphy, stress history, and tensile-failure analysis of exhumed analogs

DOE PAGES

Petrie, E. S.; Evans, J. P.; Bauer, S. J.

2014-11-01

In this study, the sedimentologic and tectonic histories of clastic cap rocks and their inherent mechanical properties control the nature of permeable fractures within them. The migration of fluid through mm- to cm-scale fracture networks can result in focused fluid flow allowing hydrocarbon production from unconventional reservoirs or compromising the seal integrity of fluid traps. To understand the nature and distribution of subsurface fluid-flow pathways through fracture networks in cap-rock seals we examine four exhumed Paleozoic and Mesozoic seal analogs in Utah. We combine these outcrop analyses with subsidence analysis, paleoloading histories, and rock-strength testing data in modified Mohr–Coulomb–Griffith analysesmore » to evaluate the effects of differential stress and rock type on fracture mode.« less

Optical pressure/density measuring means

DOEpatents

Veligdan, James T.

1995-05-09

An apparatus and method for rapidly and accurately determining the pressure of a fluid medium in either a static or dynamic state. The pressure is determined by making a measurement of the velocity of a light beam that is directed through the fluid medium along a pathway that enables an integrated pressure measurement to be made along the pathway, rather than making such a measurement only at a single point in the medium. A HeNe laser is configured to emit a beam of two frequencies separated by about 2 MHz. One of these beam frequencies is directed through the fluid medium and is reflected back through the medium to a non-linear diode detector. The other beam frequency is passed directly to a diode detector without traversing said medium. The diode detector is operated to determine the frequency shift or beat frequency between the two beam frequencies. Any variation in the frequency of said reflected beam that is caused by a change in its velocity as it is passed through the fluid medium causes a change in the beat frequency. This beat frequency change is then converted to an output signal value corresponding to the pressure of the medium. The measurement instrument apparatus is remotely positioned relative to the medium being measured, thus the apparatus is immune from electro-magnetic interference and can operate in conditions of high radiation, corrosion and extraordinarily high temperature.

Optical pressure/density measuring means

DOEpatents

Veligdan, J.T.

1995-05-09

An apparatus and method are disclosed for rapidly and accurately determining the pressure of a fluid medium in either a static or dynamic state. The pressure is determined by making a measurement of the velocity of a light beam that is directed through the fluid medium along a pathway that enables an integrated pressure measurement to be made along the pathway, rather than making such a measurement only at a single point in the medium. A HeNe laser is configured to emit a beam of two frequencies separated by about 2 MHz. One of these beam frequencies is directed through the fluid medium and is reflected back through the medium to a non-linear diode detector. The other beam frequency is passed directly to a diode detector without traversing said medium. The diode detector is operated to determine the frequency shift or beat frequency between the two beam frequencies. Any variation in the frequency of said reflected beam that is caused by a change in its velocity as it is passed through the fluid medium causes a change in the beat frequency. This beat frequency change is then converted to an output signal value corresponding to the pressure of the medium. The measurement instrument apparatus is remotely positioned relative to the medium being measured, thus the apparatus is immune from electro-magnetic interference and can operate in conditions of high radiation, corrosion and extraordinarily high temperature. 4 figs.

Pathways from Birth Weight to ADHD Symptoms through Fluid Reasoning in Youth with or without Intellectual Disability.

PubMed

Morgan, Julia E; Lee, Steve S; Loo, Sandra K; Yuhan, Joshua W; Baker, Bruce L

2018-05-01

Although individual differences in fluid reasoning reliably mediate predictions of attention-deficit/hyperactivity disorder (ADHD) symptoms from birth weight in youth with typical cognitive development (TD), it is unknown if this indirect effect operates similarly in the development of ADHD symptoms secondary to intellectual disability (ID). Thus, we evaluated mediation by fluid reasoning in a longitudinal sample of 163 youth (45% female) with (n = 52) or without (n = 111) ID who were followed prospectively from age 5 to age 13. At age 9, youth completed the Arithmetic subtest of the Wechsler Intelligence Scale for Children, a measure of fluid reasoning. At ages 9 and 13, mothers and teachers separately rated youth ADHD symptoms and mothers completed a diagnostic interview. Mediation was tested via path analysis with bootstrapped confidence intervals, and moderated mediation estimated whether indirect effects differed between ID and TD youth or based on youth IQ. Controlling for demographic factors and age 9 ADHD symptoms, age 9 Arithmetic mediated birth weight and multi-method/informant age 13 ADHD symptoms, such that birth weight positively predicted Arithmetic, which negatively predicted ADHD symptoms. Neither ID status nor IQ moderated the observed indirect effect through Arithmetic, suggesting that it was similar for ID and TD youth as well as across the range of youth IQs. These findings support previous evidence that fluid reasoning, as measured by Arithmetic, may causally mediate birth weight and ADHD symptoms, and suggest that this pathway operates similarly with respect to the development of ADHD symptoms in youth with ID.

Evolution of fracture and fault-controlled fluid pathways in carbonates of the Albanides fold-thrust belt

USGS Publications Warehouse

Graham, Wall B.R.; Girbacea, R.; Mesonjesi, A.; Aydin, A.

2006-01-01

The process of fracture and fault formation in carbonates of the Albanides fold-thrust belt has been systematically documented using hierarchical development of structural elements from hand sample, outcrop, and geologic-map scales. The function of fractures and faults in fluid migration was elucidated using calcite cement and bitumen in these structures as a paleoflow indicator. Two prefolding pressure-solution and vein assemblages were identified: an overburden assemblage and a remote tectonic stress assemblage. Sheared layer-parallel pressure-solution surfaces of the overburden assemblage define mechanical layers. Shearing of mechanical layers associated with folding resulted in the formation of a series of folding assemblage fractures at different orientations, depending on the slip direction of individual mechanical layers. Prefolding- and folding-related fracture assemblages together formed fragmentation zones in mechanical layers and are the sites of incipient fault localization. Further deformation along these sites was accommodated by rotation and translation of fragmented rock, which formed breccia and facilitated fault offset across multiple mechanical layers. Strike-slip faults formed by this process are organized in two sets in an apparent conjugate pattern. Calcite cement and bitumen that accumulated along fractures and faults are evidence of localized fluid flow along fault zones. By systematic identification of fractures and faults, their evolution, and their fluid and bitumen contents, along with subsurface core and well-log data, we identify northeast-southwest-trending strike-slip faults and the associated structures as dominant fluid pathways in the Albanides fold-thrust belt. Copyright ?? 2006. The American Association of Petroleum Geologists. All rights reserved.

Starling forces drive intracranial water exchange during normal and pathological states

PubMed Central

Linninger, Andreas A.; Xu, Colin; Tangen, Kevin; Hartung, Grant

2017-01-01

Aim To quantify the exchange of water between cerebral compartments, specifically blood, tissue, perivascular pathways, and cerebrospinal fluid-filled spaces, on the basis of experimental data and to propose a dynamic global model of water flux through the entire brain to elucidate functionally relevant fluid exchange phenomena. Methods The mechanistic computer model to predict brain water shifts is discretized by cerebral compartments into nodes. Water and species flux is calculated between these nodes across a network of arcs driven by Hagen-Poiseuille flow (blood), Darcy flow (interstitial fluid transport), and Starling’s Law (transmembrane fluid exchange). Compartment compliance is accounted for using a pressure-volume relationship to enforce the Monro-Kellie doctrine. This nonlinear system of differential equations is solved implicitly using MATLAB software. Results The model predictions of intraventricular osmotic injection caused a pressure rise from 10 to 22 mmHg, followed by a taper to 14 mmHg over 100 minutes. The computational results are compared to experimental data with R2 = 0.929. Moreover, simulated osmotic therapy of systemic (blood) injection reduced intracranial pressure from 25 to 10 mmHg. The modeled volume and intracranial pressure changes following cerebral edema agree with experimental trends observed in animal models with R2 = 0.997. Conclusion The model successfully predicted time course and the efficacy of osmotic therapy for clearing cerebral edema. Furthermore, the mathematical model implicated the perivascular pathways as a possible conduit for water and solute exchange. This was a first step to quantify fluid exchange throughout the brain. PMID:29308830

Pathways for abiotic organic synthesis at submarine hydrothermal fields.

PubMed

McDermott, Jill M; Seewald, Jeffrey S; German, Christopher R; Sylva, Sean P

2015-06-23

Arguments for an abiotic origin of low-molecular weight organic compounds in deep-sea hot springs are compelling owing to implications for the sustenance of deep biosphere microbial communities and their potential role in the origin of life. Theory predicts that warm H2-rich fluids, like those emanating from serpentinizing hydrothermal systems, create a favorable thermodynamic drive for the abiotic generation of organic compounds from inorganic precursors. Here, we constrain two distinct reaction pathways for abiotic organic synthesis in the natural environment at the Von Damm hydrothermal field and delineate spatially where inorganic carbon is converted into bioavailable reduced carbon. We reveal that carbon transformation reactions in a single system can progress over hours, days, and up to thousands of years. Previous studies have suggested that CH4 and higher hydrocarbons in ultramafic hydrothermal systems were dependent on H2 generation during active serpentinization. Rather, our results indicate that CH4 found in vent fluids is formed in H2-rich fluid inclusions, and higher n-alkanes may likely be derived from the same source. This finding implies that, in contrast with current paradigms, these compounds may form independently of actively circulating serpentinizing fluids in ultramafic-influenced systems. Conversely, widespread production of formate by ΣCO2 reduction at Von Damm occurs rapidly during shallow subsurface mixing of the same fluids, which may support anaerobic methanogenesis. Our finding of abiogenic formate in deep-sea hot springs has significant implications for microbial life strategies in the present-day deep biosphere as well as early life on Earth and beyond.

Pathways for abiotic organic synthesis at submarine hydrothermal fields

PubMed Central

McDermott, Jill M.; Seewald, Jeffrey S.; German, Christopher R.; Sylva, Sean P.

2015-01-01

Arguments for an abiotic origin of low-molecular weight organic compounds in deep-sea hot springs are compelling owing to implications for the sustenance of deep biosphere microbial communities and their potential role in the origin of life. Theory predicts that warm H2-rich fluids, like those emanating from serpentinizing hydrothermal systems, create a favorable thermodynamic drive for the abiotic generation of organic compounds from inorganic precursors. Here, we constrain two distinct reaction pathways for abiotic organic synthesis in the natural environment at the Von Damm hydrothermal field and delineate spatially where inorganic carbon is converted into bioavailable reduced carbon. We reveal that carbon transformation reactions in a single system can progress over hours, days, and up to thousands of years. Previous studies have suggested that CH4 and higher hydrocarbons in ultramafic hydrothermal systems were dependent on H2 generation during active serpentinization. Rather, our results indicate that CH4 found in vent fluids is formed in H2-rich fluid inclusions, and higher n-alkanes may likely be derived from the same source. This finding implies that, in contrast with current paradigms, these compounds may form independently of actively circulating serpentinizing fluids in ultramafic-influenced systems. Conversely, widespread production of formate by ΣCO2 reduction at Von Damm occurs rapidly during shallow subsurface mixing of the same fluids, which may support anaerobic methanogenesis. Our finding of abiogenic formate in deep-sea hot springs has significant implications for microbial life strategies in the present-day deep biosphere as well as early life on Earth and beyond. PMID:26056279

[EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

PubMed

Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

2015-01-01

The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

Silica Nanofiber Combat Hemostat (SINCH)

DTIC Science & Technology

2008-10-13

1.5mg 0.6 65 205 High aspect ratio silica fibers (30um x 60nm) 9mg 0.63 58.9 140 Kaolin (TEG control) 0.2mg n/a 59.8 155 TiO2 high aspect ratio...high surface area to volume ratio and thus the material is difficult to handle in an uncontrolled environment. It is easily dispersed and is not easy

The Navy Medical Technology Watch: Hemostatic Dressing Products for the Battlefield

DTIC Science & Technology

2006-09-09

composition and ingredients, external bleeding cessation agents all work to help the rapid formation of a thrombus (clot) or other blockage at the...clotting agent Contraindicated for internal bleeding or deep tissue wounds Collagen. Collagen-like natural substances are created from chemically...2003) Experimental (swine) Complex groin injury, arterial, venous QuikClot produced 0% mortality; RDH had a 66% mortality rate. QuikClot

Novel multi-functional fluid flow device for studying cellular mechanotransduction

PubMed Central

Lyons, James S.; Iyer, Shama R.; Lovering, Richard M.; Ward, Christopher W.; Stains, Joseph P.

2016-01-01

Cells respond to their mechanical environment by initiating multiple mechanotransduction signaling pathways. Defects in mechanotransduction have been implicated in a number of pathologies; thus, there is need for convenient and efficient methods for studying the mechanisms underlying these processes. A widely used and accepted technique for mechanically stimulating cells in culture is the introduction of fluid flow on cell monolayers. Here, we describe a novel, multifunctional fluid flow device for exposing cells to fluid flow in culture. This device integrates with common lab equipment including routine cell culture plates and peristaltic pumps. Further, it allows the fluid flow treated cells to be examined with outcomes at the cell and molecular level. We validated the device using the biologic response of cultured UMR-106 osteoblast-like cells in comparison to a commercially available system of laminar sheer stress to track live cell calcium influx in response to fluid flow. In addition, we demonstrate the fluid flow-dependent activation of phospho-ERK in these cells, consistent with the findings in other fluid flow devices. This device provides a low cost, multi-functional alternative to currently available systems, while still providing the ability to generate physiologically relevant conditions for studying processes involved in mechanotransduction in vitro. PMID:27887728

Fluid source inferred from strontium isotopes in pore fluid and carbonate recovered during Expedition 337 off Shimokita, Japan

NASA Astrophysics Data System (ADS)

Hong, W.; Moen, N.; Haley, B. A.

2013-12-01

IODP Expedition 337 was designed to understand the relationship between a deep-buried (2000 meters below seafloor) hydrocarbon reservoir off the Shimokita peninsula (Japan), and the microbial community that this carbon reservoir sustains at such depth. Understanding sources and pathways of flow of fluids that carry hydrocarbons, nutrients, and other reduced components is of particular interest to fulfilling the expedition objectives, since this migrating fluid supports microbial activity not only of the deep-seated communities but also to the shallow-dwelling organisms. To this aim, the concentration and isotopic signature of Sr can be valuable due to that it is relatively free from biogenic influence and pristine in terms of drill fluid contamination. From the pore water Sr profile, concentration gradually increases from 1500 to 2400 mbsf. The depth where highest Sr concentration is observed corresponds to the depths where couple layers of carbonate were observed. Such profile suggests an upward-migrating fluid carries Sr from those deep-seated carbonate layers (>2400 mbsf) to shallower sediments. To confirm this inference, pore water, in-situ formation fluid, and carbonate samples were analyzed for Sr isotopes to investigate the fluid source.

Assessment of effects of phenolic fractions from leaves and petals of dandelion in selected components of hemostasis.

PubMed

Lis, Bernadetta; Jędrejek, Dariusz; Stochmal, Anna; Olas, Beata

2018-05-01

Aerial parts and roots of Taraxacum officinale (dandelion) have been found to be rich sources of polyphenols, including cinnamic acid derivatives, flavonoids and triterpenoids, which exert different biological activities, such as anti-inflammatory, anticancer and antimicrobial. Additionally, the whole plant is recognized as safe and well tolerated by humans, with no reported adverse effects. Nowadays, dandelion is a commonly available dietary supplement and a component of pharmaceutical preparations used for the treatment of bladder, liver, and spleen. Nevertheless, the effect of dandelion on blood platelets and plasma - components of hemostasis involved in the functioning of a cardiovascular system and linked with various cardiovascular diseases, has not been studied yet. Thus, the main objective of our in vitro experiments was to examine the anti-platelet and antioxidant properties of four standardized dandelion phenolic fractions, i.e. leaves 50% and 85% methanol fractions, and petals 50% and 85% methanol fractions, in blood platelets. Additionally, aforementioned plant preparations were investigated for hemostatic activity in plasma, using three selected hemostatic parameters: the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). None of the studied dandelion fractions, caused the damage of human blood platelets, at the whole tested range. The inhibition of lipid peroxidation in platelets treated with H 2 O 2 /Fe (the donor of OH) was observed for two fractions: leaves and petals 50% fractions, both at the dose 50 μg/mL. Analysis of the effect on the coagulation activity of human plasma demonstrated that three fractions: petals 50% fraction, and leaves and petals 85% fractions, significantly prolonged the thrombin time, at the whole tested range. On the contrary, none of the fractions changed the APTT and the PT. The obtained results demonstrate that dandelion preparations, based on aerial parts, especially rich in hydroxycinnamic acid derivatives (leaves and petals 50% fractions) are promising plant materials exerting both antioxidant and anticoagulant activities of the hemostatic system that is beneficial in the prevention and treatment of cardiovascular diseases. Published by Elsevier Ltd.

Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients.

PubMed

Bai, Yu; Chen, Dong-Feng; Wang, Rong-Quan; Chen, You-Xiang; Shi, Rui-Hua; Tian, De-An; Chen, Huifang; Eklund, Stefan; Li, Zhao-Shen

2015-11-01

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China. AstraZeneca. ClinicalTrials.gov identifier, NCT01757275.

Gelatin-thrombin hemostatic matrix in neurosurgical procedures: hemostasis effectiveness and economic value of clinical and surgical procedure-related benefits.

PubMed

Esposito, Felice; Cappabianca, Paolo; Angileri, Filippo F; Cavallo, Luigi M; Priola, Stefano M; Crimi, Salvatore; Solari, Domenico; Germanò, Antonino F; Tomasello, Francesco

2016-07-26

Gelatin-thrombin hemostatic matrix (FloSeal®) use is associated with shorter surgical times and less blood loss, parameters that are highly valued in neurosurgical procedures. We aimed to assess the effectiveness of gelatin-thrombin in neurosurgical procedures and estimate its economic value. In a 6-month retrospective evaluation at 2 hospitals, intraoperative and postoperative information were collected from patients undergoing neurosurgical procedures where bleeding was controlled with gelatin-thrombin matrix or according to local bleeding control guidelines (control group). Study endpoints were: length of surgery, estimated blood loss, hospitalization duration, blood units utilized, intensive care unit days, postoperative complications, and time-to-recovery. Statistical methods compared endpoints between the gelatin-thrombin and control groups and resource utilization costs were estimated. Seventy-eight patients (38 gelatin-thrombin; 40 control) were included. Gelatin-thrombin was associated with a shorter surgery duration than control 166±40 versus 185±55, p=0.0839); a lower estimated blood loss (185±80 versus 250±95ml; p=0.0017); a shorter hospital stay (10±3 versus 13±3 days; p<0.001); fewer intensive care unit days (10 days/3 patients and 20 days/4 patients); and shorter time-to-recovery (3±2.2 versus 4±2.8 weeks; p=0861). Fewer gelatin-thrombin patients experienced postoperative complications (3 minor) than the control group (5 minor; 3 major). No gelatin-thrombin patient required blood transfusion; 5 units were administered in the control group. The cost of gelatin-thrombin (€268.40/unit) was offset by the shorter surgery duration (difference of 19 minutes at €858 per hour) and the economic value of improved the other endpoint outcomes (ie, shorter hospital stay, less blood loss/lack of need for transfusion, fewer intensive care unit days, and complications). Gelatin-thrombin hemostatic matrix use in patients undergoing neurosurgical procedures was associated with better intra- and post-operative parameters than conventional hemostasis methods, with these parameters having substantial economic benefits.

A randomized comparative trial of OTSC and Padlock for upper GI hemostasis in a standardized experimental setting.

PubMed

Prosst, Ruediger L; Kratt, Thomas

2017-04-01

Upper gastrointestinal bleeding (UGIB) is the key emergency situation in clinical endoscopy and is traditionally treated with injection, thermal or through the scope clipping therapy. Mortality rates are in the range of 8-10% and demand new treatment approaches. The Over-The-Scope Clip (OTSC ® ) has been described as a very effective hemostatic device in UGIB. We compared OTSC with the Padlock™ device in an established pre-clinical setting. Our test-bed consisted of the biohybrid EASIE model using soft silicone tubes, tunneled into the gastric wall and surfacing at a mucosa defect, representing the bleeding site. After successful deployment of the OTSC and Padlock devices on the spurting ulcer bleed (Forrest Ia) the vessel tubes were pressurized with a manometer to 120 mmHg. Tight closure at this pressure was defined as successful hemostasis (primary endpoint). N = 11 procedures were done with each device. Statistical testing was done using Fisher's exact test. Sample size was adjusted to an assumed α-error of 5% (two-sided test) and a power of 80%. Technically correct placement of the respective hemostatic device was achieved in all procedures. A statistically significant difference was found in the primary endpoint. In OTSC the success proportion was 100%; 11/11 (95% KI 74.1% to 100%); in Padlock it was 0%; 0/11 (95% KI 0%-25.8%). This means that no bleeding was stopped by Padlock. The mean value of perfusion pressure resistance was 300 mmHg (cut-off) for OTSC and 9.2 ± 8.4 mmHg for Padlock. Our data on hemostatic function of OTSC coincide with the clinical literature and earlier pre-clinical studies in the EASIE model, which is widely accepted as a realistic and effective simulation system for clinical conditions. The inability of Padlock to stop hemorrhage may be due to design differences and, thus, its limitation in providing tight sealing of the clipped tissue. Different types of endoscope-tip mounted clips have different performances. OTSC consistently stops simulated spurting bleeding, Padlock fails to do so. These differences are statistically significant.

Spatial and Temporal Characteristics of Historical Oil and Gas Wells in Pennsylvania: Implications for New Shale Gas Resources.

PubMed

Dilmore, Robert M; Sams, James I; Glosser, Deborah; Carter, Kristin M; Bain, Daniel J

2015-10-20

Recent large-scale development of oil and gas from low-permeability unconventional formations (e.g., shales, tight sands, and coal seams) has raised concern about potential environmental impacts. If left improperly sealed, legacy oil and gas wells colocated with that new development represent a potential pathway for unwanted migration of fluids (brine, drilling and stimulation fluids, oil, and gas). Uncertainty in the number, location, and abandonment state of legacy wells hinders environmental assessment of exploration and production activity. The objective of this study is to apply publicly available information on Pennsylvania oil and gas wells to better understand their potential to serve as pathways for unwanted fluid migration. This study presents a synthesis of historical reports and digital well records to provide insights into spatial and temporal trends in oil and gas development. Areas with a higher density of wells abandoned prior to the mid-20th century, when more modern well-sealing requirements took effect in Pennsylvania, and areas where conventional oil and gas production penetrated to or through intervals that may be affected by new Marcellus shale development are identified. This information may help to address questions of environmental risk related to new extraction activities.

Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN.

PubMed

Iatropoulos, Paraskevas; Daina, Erica; Curreri, Manuela; Piras, Rossella; Valoti, Elisabetta; Mele, Caterina; Bresin, Elena; Gamba, Sara; Alberti, Marta; Breno, Matteo; Perna, Annalisa; Bettoni, Serena; Sabadini, Ettore; Murer, Luisa; Vivarelli, Marina; Noris, Marina; Remuzzi, Giuseppe

2018-01-01

Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment. Copyright © 2018 by the American Society of Nephrology.

Dysregulation of metabolic pathways in a mouse model of allergic asthma.

PubMed

Quinn, K D; Schedel, M; Nkrumah-Elie, Y; Joetham, A; Armstrong, M; Cruickshank-Quinn, C; Reisdorph, R; Gelfand, E W; Reisdorph, N

2017-09-01

Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function. In this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6 hour, 24 hour, and 48 hour after the last challenge. Samples were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Airway hyper-responsiveness (AHR) measurements and differential cell counts were performed. In total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (P=6.6×10 -5 ), arginine and proline metabolism (P=1.12×10 -7 ), glycerophospholipid metabolism (P=1.3×10 -10 ), and the neurotrophin signaling pathway (P=7.0×10 -6 ). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxylate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia. These findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

24th International Symposium on Ballistics

DTIC Science & Technology

2008-09-26

production Samples dimensions were 0.3x0.05 m. Test set up Gas gun 5.5 mm diameter steel spheres and sabot Velocity measuring  systems High speed rate...Oilwell perforators – small caliber shaped charges – create the pathway for oil or gas to flow from the reservoir rock into the wellbore  Deep, clean ...overburden, tectonic) – Pore fluid pressure – Pore fluid type ( liquid vs. gas ) Background  Geomechanics considerations: – In-situ stresses (“total

Secondary migration and leakage of methane from a major tight-gas system

NASA Astrophysics Data System (ADS)

Wood, James M.; Sanei, Hamed

2016-11-01

Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere.

Secondary migration and leakage of methane from a major tight-gas system

PubMed Central

Wood, James M.; Sanei, Hamed

2016-01-01

Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere. PMID:27874012

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.

PubMed

Plog, Benjamin A; Nedergaard, Maiken

2018-01-24

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.

The glymphatic system in CNS health and disease: past, present and future

PubMed Central

Plog, Benjamin A.; Nedergaard, Maiken

2018-01-01

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here we review the role of the glymphatic pathway in CNS physiology, factors known to regulate glymphatic flow, and pathologic processes where a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, will also be discussed. PMID:29195051

Preliminary Results from an Integrated Airborne EM and Aeromagnetic Survey in Yellowstone National Park

NASA Astrophysics Data System (ADS)

Dickey, K.; Holbrook, W. S.; Finn, C.; Auken, E.; Carr, B.; Sims, K. W. W.; Bedrosian, P.; Lowenstern, J. B.; Hurwitz, S.; Pedersen, J. B. B.

2017-12-01

Yellowstone National Park hosts over 10,000 thermal features (e.g. geysers, fumaroles, mud pots, and hot springs), yet little is known about the circulation depth of meteoric water feeding these features, nor the lithological and structural bounds on the pathways that guide deep, hot fluids to the surface. Previous near-surface geophysical studies have been effective in imaging shallow hydrothermal pathways in some areas of the park, but these methods are difficult to conduct over the large areas needed to characterize entire hydrothermal systems. Transient electromagnetic (TEM) soundings and 2D direct current (DC) resistivity profiles show that hydrothermal fluids at active sites have a higher electrical conductivity than the surrounding hydrothermally inactive areas. For that reason, airborne TEM is an effective method to characterize large areas and identify hydrothermally active and inactive zones using electrical conductivity. Aeromagnetic data have been useful in mapping faults that localize hot springs, making the integration of aeromagnetic and EM data effective for structurally characterizing fluid pathways. Here we present the preliminary results from an airborne transient electromagnetic (TEM) and magnetic survey acquired jointly by the U.S. Geological Survey (USGS) and the University of Wyoming (UW) in November 2016. We integrate the EM and magnetic data for the purpose of edge detection of rhyolite flow boundaries as well as source depth of hydrothermal features. The maximum horizontal gradient technique applied on magnetic data is a useful tool that used to estimate source depth as well as indicate faults and fractures. The integration of EM with magnetics allows us to distinguish hydrothermally altered fault systems that guide fluids in the subsurface. We have used preliminary 2D inversions of EM from Aarhus Workbench to delineate rhyolite flow edges in the upper 300-600 meters and cross-checked those boundaries with the aeromagnetic map.

Episodic fluid expulsion and fluid pathways during high-pressure dehydration of serpentinite

NASA Astrophysics Data System (ADS)

Padrón-Navarta, J.; Garrido, C. J.; López Sánchez-Vizcaíno, V.; Gómez-Pugnaire, M.; Tommasi, A.; Marchesi, C.

2011-12-01

Our understanding of subduction zone processes is tightly connected to our knowledge of the cycling of volatiles in the Earth, namely the loci of devolatilization reactions and the fluid migration mechanism. The exact nature of fluid pathways at high-pressure conditions is poorly known and still highly speculative. The study of metamorphic terrains that record main dehydration reaction are, thus, an invaluable tool to decipher the mechanism for fluid expulsion. Among other dehydration reactions in subduction zones, the antigorite (Atg) breakdown is rather discontinuous, releases the largest amount of fluids (ca. 9 wt. %) and is considered to have important seismological implications. The antigorite dehydration front in the Cerro del Almirez (Betic Cordillera, Spain) offers, thus, an unique opportunity to investigate the dynamics of fluid expulsion through the study of micro- and macrotextures recorded in the prograde assemblage (chlorite harzburgite). Chl-harzburgites show two textures interspersed in decameter-sized domains: granoblastic and spinifex-like. Both were formed under similar P-T conditions (~1.6-1.9 GPa and 680-710°C)). We ascribe the change in texture to shifts of the growth rate due to temporal and spatial fluctuations of the affinity of the Atg-breakdown reaction. These fluctuations are driven by cyclic variations of the excess fluid pressure which are ultimately controlled by the hydrodynamics of deserpentinization fluid expulsion. Crystallization at a low affinity of the reaction, correspondig to the granoblastic texture, may be attained if fluids are slowly drained out from the dehydration front. During the advancement of the dehydration front, overpressured domains are left behind preserving highly metastable Atg-serpentinite domains. Brittle failure results in a sudden drop of the fluid pressure, and a displacement of Atg equilibrium towards the prograde products that crystallizes at a high affinity of the reaction (spinifex-like texture). Evidences of brittle failure are found along grain-size reduction zones (GSRZ), a few mm to meters wide, which form roughly planar conjugate structures and crosscut the metamorphic texture. GSRZ are characterized by (1) sharp, irregular shapes and abrupt terminations contacts with undeformed metaperidotite, (2) an important reduction of the olivine grain size (60-250 μm), and (3) decrease in the opx modal amount. Analysis of olivine crystal-preferred orientations in GSRZ shows similar patterns, but a higher dispersion than in neighboring metaperidotite. These structures are interpreted as due to hydrofracturing allowing for the formation of high permeability channelways for overpressured fluids. This textural bimodality (granofels and spinifex-like) and the record of brittle failure witness a unique example of feedback between cyclic metamorphic fluid expulsion, reaction rates, and deformation in the Atg-dehydrating system.

microRNA Profiling of Amniotic Fluid: Evidence of Synergy of microRNAs in Fetal Development.

PubMed

Sun, Tingting; Li, Weiyun; Li, Tianpeng; Ling, Shucai

2016-01-01

Amniotic fluid (AF) continuously exchanges molecules with the fetus, playing critical roles in fetal development especially via its complex components. Among these components, microRNAs are thought to be transferred between cells loaded in microvesicles. However, the functions of AF microRNAs remain unknown. To date, few studies have examined microRNAs in amniotic fluid. In this study, we employed miRCURY Locked Nucleotide Acid arrays to profile the dynamic expression of microRNAs in AF from mice on embryonic days E13, E15, and E17. At these times, 233 microRNAs were differentially expressed (p< 0.01), accounting for 23% of the total Mus musculus microRNAs. These differentially-expressed microRNAs were divided into two distinct groups based on their expression patterns. Gene ontology analysis showed that the intersectional target genes of these differentially-expressed microRNAs were mainly distributed in synapse, synaptosome, cell projection, and cytoskeleton. Pathway analysis revealed that the target genes of the two groups of microRNAs were synergistically enriched in axon guidance, focal adhesion, and MAPK signaling pathways. MicroRNA-mRNA network analysis and gene- mapping showed that these microRNAs synergistically regulated cell motility, cell proliferation and differentiation, and especially the axon guidance process. Cancer pathways associated with growth and proliferation were also enriched in AF. Taken together, the results of this study are the first to show the functions of microRNAs in AF during fetal development, providing novel insights into interpreting the roles of AF microRNAs in fetal development.

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

PubMed

Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla.

PubMed

Pannabecker, Thomas L

2013-04-01

Comparative studies of renal structure and function have potential to provide insights into the urine-concentrating mechanism of the mammalian kidney. This review focuses on the tubular transport pathways for water and urea that play key roles in fluid and solute movements between various compartments of the rodent renal inner medulla. Information on aquaporin water channel and urea transporter expression has increased our understanding of functional segmentation of medullary thin limbs of Henle's loops, collecting ducts, and vasa recta. A more complete understanding of membrane transporters and medullary architecture has identified new and potentially significant interactions between these structures and the interstitium. These interactions are now being introduced into our concept of how the inner medullary urine-concentrating mechanism works. A variety of regulatory pathways lead directly or indirectly to variable patterns of fluid and solute movements among the interstitial and tissue compartments. Animals with the ability to produce highly concentrated urine, such as desert species, are considered to exemplify tubular structure and function that optimize urine concentration. These species may provide unique insights into the urine-concentrating process.(1)

Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla

PubMed Central

2013-01-01

Comparative studies of renal structure and function have potential to provide insights into the urine-concentrating mechanism of the mammalian kidney. This review focuses on the tubular transport pathways for water and urea that play key roles in fluid and solute movements between various compartments of the rodent renal inner medulla. Information on aquaporin water channel and urea transporter expression has increased our understanding of functional segmentation of medullary thin limbs of Henle's loops, collecting ducts, and vasa recta. A more complete understanding of membrane transporters and medullary architecture has identified new and potentially significant interactions between these structures and the interstitium. These interactions are now being introduced into our concept of how the inner medullary urine-concentrating mechanism works. A variety of regulatory pathways lead directly or indirectly to variable patterns of fluid and solute movements among the interstitial and tissue compartments. Animals with the ability to produce highly concentrated urine, such as desert species, are considered to exemplify tubular structure and function that optimize urine concentration. These species may provide unique insights into the urine-concentrating process.1 PMID:23364530

Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid.

PubMed

Fischer, S Taylor; Lili, Loukia N; Li, Shuzhao; Tran, ViLinh T; Stewart, Kim B; Schwartz, Charles E; Jones, Dean P; Sherman, Stephanie L; Fridovich-Keil, Judith L

2017-10-01

Decades of public health research have documented that smoking in pregnancy poses significant health risks to both mother and child. More recent studies have shown that even passive maternal exposure to secondhand smoke associates with negative birth outcomes. However, the mechanisms linking exposure to outcomes have remained obscure. As a first step toward defining the metabolic consequence of low-level nicotine exposure on fetal development, we conducted an untargeted metabolomic analysis of 81 paired samples of maternal serum and amniotic fluid collected from karyotypically normal pregnancies in the second trimester. By comparing the m/z and retention times of our mass spectral features with confirmed standards, we identified cotinine, a nicotine derivative, and used the calculated cotinine concentrations to classify our maternal serum samples into exposure groups using previously defined cut-offs. We found that cotinine levels consistent with low-level maternal exposure to nicotine associated with distinct metabolic perturbations, particularly in amniotic fluid. In fact, the metabolic effects in amniotic fluid of ostensibly low-level exposed mothers showed greater overlap with perturbations previously observed in the sera of adult smokers than did the perturbations observed in the corresponding maternal sera. Dysregulated fetal pathways included aspartate and asparagine metabolism, pyrimidine metabolism, and metabolism of other amino acids. We also observed a strong negative association between level of maternal serum cotinine and acetylated polyamines in the amniotic fluid. Combined, these results confirm that low-level maternal nicotine exposure, indicated by a maternal serum cotinine level of 2-10ng/mL, is associated with striking metabolic consequences in the fetal compartment, and that the affected pathways overlap those perturbed in the sera of adult smokers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of Hemostatic Efficacy of ChitoGauze and Combat Gauze in a Lethal Femoral Arterial Injury in Swine Model

DTIC Science & Technology

2010-04-01

range of gram positive and gram negative organisms, including methicillin resistant Staphylococcus aureus ATCC33591 (MRSA), Enterococcus faecalis...range of gram positive and gram negative organisms, including methicillin resistant Staphylococcus aureus ATCC33591 (MRSA), Enterococcus faecalis...control with less blood loss than Combat Gauze in this model. Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for

Comparison of 10 Different Hemostatic Dressings in an Aortic Injury

DTIC Science & Technology

2003-02-01

lateral peritoneal recesses of the abdomen bilaterally. The rate of bleeding was quantified (grams accumulated every 10 sec- onds) in the suction...used frequently for hemostasis in dental procedures19 D5 TachoComb S Nycomed Amersham, Linz, Austria Collagen -based ( collagen from horse tendons...product with human fibrinogen and thrombin Collagen attracts and activates platelets to achieve hemostasis. D5 also had fibrinogen and thrombin, but at a

Effects of DETANONOate, a nitric oxide donor, on hemostasis in rabbits: an in vitro and in vivo thrombelastographic analysis.

PubMed

Nielsen, V G; Geary, B T; Baird, M S

2000-03-01

The purpose of this study was to determine if whole blood thrombelastographic variables (reaction time, K, alpha, and maximum amplitude) would be adversely effected by exposure to the nitric oxide (NO) donor, DETANONOate, in vitro or after alveolar instillation in vivo. Conscious rabbits (n = 10) had blood sampled from ear arteries anticoagulated with sodium citrate. The blood was then incubated with 0, 1, 5, 10, or 20 mmol/L DETANONOate for 30 minutes. Arterial blood from anesthetized rabbits (n = 4) was obtained and anticoagulated before and 60 minutes after 1 mmol/L DETANONOate (2 mL/kg) was instilled into the right lung. After incubation, all samples were placed in a thrombelastograph and recalcified, with thrombelastographic variables measured for 45 minutes. In vitro, 10 mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha compared with values observed after incubation with 0, 1, and 5 mmol/L DETANONOate. Twenty mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha and maximum amplitude values compared with all other concentrations. In vivo, DETANONOate administration did not significantly affect thrombelastographic variables. DETANONOate significantly decreased hemostatic function in vitro in a dose-dependent fashion but did not significantly affect hemostatic function in vivo.

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles

PubMed Central

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-01-01

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. PMID:28398222

Hemostatic efficacy of local chitosan linear polymer granule in an experimental sheep model with severe bleeding of arteria and vena femoralis.

PubMed

Ersoy, Gürkan; Rodoplu, Ülkümen; Yılmaz, Osman; Gökmen, Necati; Doğan, Alper; Dikme, Özgür; Aydınoğlu, Aslı; Orhon, Okyanus

2016-05-01

The aim of the present study was to evaluate the hemostatic effect of chitosan linear polymer in a sheep model with femoral bleeding. Following induction of anesthesia and intubation of sheep, groin injury was induced to initiate hemorrhage. Animals were randomly assigned to study and control groups. In the control group, absorbent pads were packed on the wound, and pressure was supplied by a weight placed over the dressing. In the study group, chitosan linear polymer was poured onto the bleeding site; absorbent pads and pressure were applied in the same manner. At 5-min intervals, bleeding was evaluated. Primary endpoint was time to hemostasis. Bleeding had stopped by the 1st interval in 5 members of the study group, and by the 2nd interval in 1 member. One sheep was excluded. The bleeding stopped after the 1st interval in 1 member of the control group and after the 2nd interval in 4 members. Bleeding stopped in 2 cases following ligation of the bleeding vessel. Hemostasis was achieved earlier in the study group, compared to the control group, and the difference was statistically significant. Hemostasis was achieved earlier following application of chitosan linear polymer.

Comparative effectiveness of epsilon-aminocaproic acid and tranexamic acid on postoperative bleeding following cardiac surgery during a national medication shortage.

PubMed

Blaine, Kevin P; Press, Christopher; Lau, Ken; Sliwa, Jan; Rao, Vidya K; Hill, Charles

2016-12-01

The aim of this study was to compare the effectiveness of epsilon-aminocaproic acid (εACA) and tranexamic acid (TXA) in contemporary clinical practice during a national medication shortage. A retrospective cohort study. The study was performed in all consecutive cardiac surgery patients (n=128) admitted to the cardiac-surgical intensive care unit after surgery at a single academic center immediately before and during a national medication shortage. Demographic, clinical, and outcomes data were compared by descriptive statistics using χ 2 and t test. Surgical drainage and transfusions were compared by multivariate linear regression for patients receiving εACA before the shortage and TXA during the shortage. In multivariate analysis, no statistical difference was found for surgical drain output (OR 1.10, CI 0.97-1.26, P=.460) or red blood cell transfusion requirement (OR 1.79, CI 0.79-2.73, P=.176). Patients receiving εACA were more likely to receive rescue hemostatic medications (OR 1.62, CI 1.02-2.55, P=.041). Substitution of εACA with TXA during a national medication shortage produced equivalent postoperative bleeding and red cell transfusions, although patients receiving εACA were more likely to require supplemental hemostatic agents. Published by Elsevier Inc.

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

PubMed

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-04-11

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly( γ -glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca 2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.

Hypertonic saline-epinephrine local injection therapy for post-endoscopic sphincterotomy bleeding: removal of blood clots using pure ethanol local injection.

PubMed

Sakai, Yuji; Tsuyuguchi, Toshio; Sugiyama, Harutoshi; Nishikawa, Takao; Kurosawa, Jo; Saito, Masayoshi; Tawada, Katsunobu; Mikata, Rintaro; Tada, Motohisa; Ishihara, Takeshi; Yokosuka, Osamu

2013-08-01

Bleeding following endoscopic sphincterotomy (EST) is a rare but unavoidable complication of the procedure. We routinely perform local injection of hypertonic saline-epinephrine (HSE) for the treatment of post-EST bleeding. Any blood clot is removed only by irrigation with water after local injection of pure ethanol into the blood clot to cause crusting. We evaluated the usefulness of this treatment method. Subjects were 8 patients (1.2%) with post-EST bleeding requiring hemostatic intervention among 682 patients undergoing EST. After determination of the bleeding point, local injection of HSE was performed. When an adherent blood clot was present, pure ethanol was injected into the blood clot and then irrigation with water was performed to remove the blood clot. Endoscopic hemostasis was successfully achieved in all the 8 patients (100%). In 4 patients (50%), the adherent blood clots were successfully removed only with pure ethanol local injection into the blood clot followed by irrigation with water. No complications of the hemostatic procedure occurred in any patients. This study indicated that hemostasis with HSE local injection can be safe and useful for the treatment of post-EST bleeding, and also that blood clot removal with pure ethanol local injection can be useful.

Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness

PubMed Central

Schaber, Marc; Leichtfried, Veronika; Fries, Dietmar; Wille, Maria; Gatterer, Hannes; Faulhaber, Martin; Würtinger, Philipp; Schobersberger, Wolfgang

2015-01-01

Introduction. The aim of the present study was to investigate whether a 12-hour exposure in a normobaric hypoxic chamber would induce changes in the hemostatic system and a procoagulant state in volunteers suffering from acute mountain sickness (AMS) and healthy controls. Materials and Methods. 37 healthy participants were passively exposed to 12.6% FiO2 (simulated altitude hypoxia of 4,500 m). AMS development was investigated by the Lake Louise Score (LLS). Prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count were measured and specific methods (i.e., thromboelastometry and a thrombin generation test) were used. Results. AMS prevalence was 62.2% (LLS cut off of 3). For the whole group, paired sample t-tests showed significant increase in the maximal concentration of generated thrombin. ROTEM measurements revealed a significant shortening of coagulation time and an increase of maximal clot firmness (InTEM test). A significant increase in maximum clot firmness could be shown (FibTEM test). Conclusions. All significant changes in coagulation parameters after exposure remained within normal reference ranges. No differences with regard to measured parameters of the hemostatic system between AMS-positive and -negative subjects were observed. Therefore, the hypothesis of the acute activation of coagulation by hypoxia can be rejected. PMID:26451374

Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness.

PubMed

Schaber, Marc; Leichtfried, Veronika; Fries, Dietmar; Wille, Maria; Gatterer, Hannes; Faulhaber, Martin; Würtinger, Philipp; Schobersberger, Wolfgang

2015-01-01

The aim of the present study was to investigate whether a 12-hour exposure in a normobaric hypoxic chamber would induce changes in the hemostatic system and a procoagulant state in volunteers suffering from acute mountain sickness (AMS) and healthy controls. 37 healthy participants were passively exposed to 12.6% FiO2 (simulated altitude hypoxia of 4,500 m). AMS development was investigated by the Lake Louise Score (LLS). Prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count were measured and specific methods (i.e., thromboelastometry and a thrombin generation test) were used. AMS prevalence was 62.2% (LLS cut off of 3). For the whole group, paired sample t-tests showed significant increase in the maximal concentration of generated thrombin. ROTEM measurements revealed a significant shortening of coagulation time and an increase of maximal clot firmness (InTEM test). A significant increase in maximum clot firmness could be shown (FibTEM test). All significant changes in coagulation parameters after exposure remained within normal reference ranges. No differences with regard to measured parameters of the hemostatic system between AMS-positive and -negative subjects were observed. Therefore, the hypothesis of the acute activation of coagulation by hypoxia can be rejected.

Differences in coagulation among Asians and Caucasians and the implication for reconstructive microsurgery.

PubMed

Singhal, Dhruv; Smorodinsky, Emmanuil; Guo, Lifei

2011-01-01

Microvascular reconstructive surgery has seen a revival with the introduction of muscle-sparing perforator flaps. Recognition of potential ethnic differences in coagulation profiles would be important to a microvascular surgeon. Based on clinical observations, we hypothesize that Asian patients have a less thrombogenic coagulation profile than Caucasians. An extensive retrospective review was performed. The annual incidence of venous thromboembolism in the United States is generally accepted to range from 70 to 120 events per 100,000 people versus 16 to 17 events per 100,000 persons in Asia. Autopsy analysis of pulmonary embolism incidence was noted to be 15% in North Americans and less than 1% in Asian populations. Thromboelastography analysis of Asian and Caucasian patients undergoing cholecystectomy revealed different hemostatic mechanisms. Comparison of Asians and Caucasians undergoing the Fontan procedure revealed significantly lower postoperative factor levels in Asians than Caucasians. Baseline comparison of factor and serum levels revealed Asians with the least thrombogenic profiles compared with other ethnic groups. Asians and Caucasians demonstrate different baseline rates of deep vein thrombosis and pulmonary embolism, different hemostatic responses to surgery, and different baseline levels of clotting factors. Further study may lead to better pre-, intra-, and postoperative care of the free flap patient based on their ethnic coagulation profile. © Thieme Medical Publishers.

Quantitative Characterization of Shear-Induced Platelet Receptor Shedding: Glycoprotein Ibα, Glycoprotein VI, and Glycoprotein IIb/IIIa.

PubMed

Chen, Zengsheng; Koenig, Steven C; Slaughter, Mark S; Griffith, Bartley P; Wu, Zhongjun J

2017-11-07

The structural integrity of platelet receptors is essential for platelets to play the normal hemostatic function. The high non-physiologic shear stress (NPSS) commonly exists in blood-contacting medical devices and has been shown to cause platelet receptor shedding. The loss of platelet receptors may impair the normal hemostatic function of platelets. The aim of this study was to quantify NPSS-induced shedding of three key receptors on the platelet surface. Human blood was subjected to the matrix of well-defined shear stresses and exposure times, generated by using a custom-designed blood-shearing device. The expression of three key platelet receptors, glycoprotein (GP) Ibα, GPVI, and GPIIb/IIIa, in sheared blood was quantified using flow cytometry. The quantitative relationship between the loss of each of the three receptors on the platelet surface and shear condition (shear stress level and exposure time) was explored. It was found that these relationships followed well the power law functional form. The coefficients of the power law models for the shear-induced shedding of these platelet receptors were derived with coefficients of determination (R) of 0.77, 0.73, and 0.78, respectively. The power law models with these coefficients may be potentially used to predict the shear-induced platelet receptor shedding of human blood.

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis.

PubMed

Farris, Manuela; Bastianelli, Carlo; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-10-01

The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel. Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed. Expert commentary: Overall, the picture is reassuring: the use of natural estrogens and of new generation progestins has reduced pro-coagulatory changes in healthy subjects, although the observed differences in the risk of venous thromboembolism between second and third generation progestins is still incompletely understood. At the same time, there still is a need for large comparative and surveillance studies before firm conclusions can be drawn. At any rate, available evidence indicates that hemostatic effects of the newer COC, especially those utilizing natural estrogens, are minimal and often remain with the normal range.

Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms

PubMed Central

Anderson, Debra F.; Cheung, Cecilia Y.

2014-01-01

Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport. PMID:25186112

Complementary Cognitive Capabilities, Economic Decision-Making, and Aging

PubMed Central

Li, Ye; Baldassi, Martine; Johnson, Eric J.; Weber, Elke U.

2014-01-01

Fluid intelligence decreases with age, yet evidence about age declines in decision-making quality is mixed: Depending on the study, older adults make worse, equally good, or even better decisions than younger adults. We propose a potential explanation for this puzzle, namely that age differences in decision performance result from the interplay between two sets of cognitive capabilities that impact decision making, one in which older adults fare worse (i.e., fluid intelligence) and one in which they fare better (i.e., crystallized intelligence). Specifically, we hypothesized that older adults’ higher levels of crystallized intelligence can provide an alternate pathway to good decisions when the fluid intelligence pathway declines. The performance of older adults relative to younger adults therefore depends on the relative importance of each type of intelligence for the decision at hand. We tested this complementary capabilities hypothesis in a broad sample of younger and older adults, collecting a battery of standard cognitive measures and measures of economically important decision-making “traits”—including temporal discounting, loss aversion, financial literacy, and debt literacy. We found that older participants performed as well as or better than younger participants on these four decision-making measures. Structural equation modeling verified our hypothesis: Older participants’ greater crystallized intelligence offset their lower levels of fluid intelligence for temporal discounting, financial literacy, and debt literacy, but not for loss aversion. These results have important implications for public policy and for the design of effective decision environments for older adults. PMID:24040999

Water-rich bending faults at the Middle America Trench

NASA Astrophysics Data System (ADS)

Naif, Samer; Key, Kerry; Constable, Steven; Evans, Rob L.

2015-09-01

The portion of the Central American margin that encompasses Nicaragua is considered to represent an end-member system where multiple lines of evidence point to a substantial flux of subducted fluids. The seafloor spreading fabric of the incoming Cocos plate is oriented parallel to the trench such that flexural bending at the outer rise optimally reactivates a dense network of normal faults that extend several kilometers into the upper mantle. Bending faults are thought to provide fluid pathways that lead to serpentinization of the upper mantle. While geophysical anomalies detected beneath the outer rise have been interpreted as broad crustal and upper mantle hydration, no observational evidence exists to confirm that bending faults behave as fluid pathways. Here we use seafloor electromagnetic data collected across the Middle America Trench (MAT) offshore of Nicaragua to create a comprehensive electrical resistivity image that illuminates the infiltration of seawater along bending faults. We quantify porosity from the resistivity with Archie's law and find that our estimates for the abyssal plain oceanic crust are in good agreement with independent observations. As the Cocos crust traverses the outer rise, the porosity of the dikes and gabbros progressively increase from 2.7% and 0.7% to 4.8% and 1.7%, peaking within 20 km of the trench axis. We conclude that the intrusive crust subducts twice as much pore water as previously thought, significantly raising the flux of fluid to the seismogenic zone and the mantle wedge.

Complementary cognitive capabilities, economic decision making, and aging.

PubMed

Li, Ye; Baldassi, Martine; Johnson, Eric J; Weber, Elke U

2013-09-01

Fluid intelligence decreases with age, yet evidence about age declines in decision-making quality is mixed: Depending on the study, older adults make worse, equally good, or even better decisions than younger adults. We propose a potential explanation for this puzzle, namely that age differences in decision performance result from the interplay between two sets of cognitive capabilities that impact decision making, one in which older adults fare worse (i.e., fluid intelligence) and one in which they fare better (i.e., crystallized intelligence). Specifically, we hypothesized that older adults' higher levels of crystallized intelligence can provide an alternate pathway to good decisions when the fluid intelligence pathway declines. The performance of older adults relative to younger adults therefore depends on the relative importance of each type of intelligence for the decision at hand. We tested this complementary capabilities hypothesis in a broad sample of younger and older adults, collecting a battery of standard cognitive measures and measures of economically important decision-making "traits"--including temporal discounting, loss aversion, financial literacy, and debt literacy. We found that older participants performed as well as or better than younger participants on these four decision-making measures. Structural equation modeling verified our hypothesis: Older participants' greater crystallized intelligence offset their lower levels of fluid intelligence for temporal discounting, financial literacy, and debt literacy, but not for loss aversion. These results have important implications for public policy and for the design of effective decision environments for older adults.

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

PubMed Central

2015-01-01

Background Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. Methods We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Results Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Conclusions Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis. PMID:26040285

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets.

PubMed

Cordeiro, Ana Paula; Silva Pereira, Rosiane Aparecida; Chapeaurouge, Alex; Coimbra, Clarice Semião; Perales, Jonas; Oliveira, Guilherme; Sanchez Candiani, Talitah Michel; Coimbra, Roney Santos

2015-01-01

Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis.

A Framework for Fracture Network Formation in Overpressurised Impermeable Shale: Deformability Versus Diagenesis

NASA Astrophysics Data System (ADS)

Alevizos, Sotiris; Poulet, Thomas; Sari, Mustafa; Lesueur, Martin; Regenauer-Lieb, Klaus; Veveakis, Manolis

2017-03-01

Understanding the formation, geometry and fluid connectivity of nominally impermeable unconventional shale gas and oil reservoirs is crucial for safe unlocking of these vast energy resources. We present a recent discovery of volumetric instabilities of ductile materials that may explain why impermeable formations become permeable. Here, we present the fundamental mechanisms, the critical parameters and the applicability of the novel theory to unconventional reservoirs. We show that for a reservoir under compaction, there exist certain ambient and permeability conditions at which diagenetic (fluid-release) reactions may provoke channelling localisation instabilities. These channels are periodically interspersed in the matrix and represent areas where the excess fluid from the reaction is segregated at high velocity. We find that channelling instabilities are favoured from pore collapse features for extremely low-permeability formations and fluid-release diagenetic reactions, therefore providing a natural, periodic network of efficient fluid pathways in an otherwise impermeable matrix (i.e. fractures). Such an outcome is of extreme importance the for exploration and extraction phases of unconventional reservoirs.

A role for transforming growth factor-{beta} apoptotic signaling pathway in liver injury induced by ingestion of water contaminated with high levels of Cr(VI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rafael, A.I.; Almeida, A.; Santos, P.

2007-10-15

Hexavalent chromium [Cr(VI)] exposure is commonly associated with lung cancer. Although other adverse health effects have been reported, some authors, on assuming that orally ingested Cr(VI) is efficiently detoxified upon reduction by body fluids, believe that Cr(VI) do not target cells other than respiratory tract cells. In rodents, ingested Cr(VI)-contaminated water was reported to induce, in the liver, increases in TGF-{beta} transcripts. As TGF-{beta} dependent signaling pathways are closely associated with hepatic injury, the present study was undertaken addressing two specific issues: the effects of ingestion of water contaminated with high levels of Cr(VI) in rat liver structure and function;more » and the role of the TGF-{beta} pathway in Cr(VI)-induced liver injury. Examination of Wistar rats exposed to 20 ppm Cr(VI)-contaminated water for 10 weeks showed increased serum glucose and alanine aminotransferase (ALT) levels. Liver histological examination revealed hepatocellular apoptosis, further confirmed by immunohystochemical study of Caspase 3 expression. Liver gene expression analysis revealed increased expression of Smad2/Smad4 and Dapk, suggesting the involvement of the TGF-{beta} pathway in the apoptotic process. Since no changes in Smad3 expression were observed it appears apoptosis is using a Smad3-independent pathway. Increased expression of both Caspase 8 and Daxx genes suggests also the involvement of the Fas pathway. Gene expression analysis also revealed that a p160{sup ROCK}-Rho-independent pathway operates, leading to cell contraction and membrane blebbing, characteristic apoptotic features. These findings suggest that either the amount of Cr(VI) ingested overwhelmed the body fluids reductive capacity or some Cr(VI) escapes the reductive protection barrier, thus targeting the liver and inducing apoptosis.« less