Switching from Intravenous to Oral Tacrolimus Reduces its Blood Concentration in Paediatric Cancer Patients.

BACKGROUND/AIM: Tacrolimus is an essential immunosuppressant for successful allogeneic haematopoietic stem cell transplantation (Allo-HSCT). This study aimed to examine the change in the blood concentration of tacrolimus during switching from intravenous to oral administration in allo-HSCT for paediatric cancer to predict the optimal dosage. PATIENTS AND METHODS: We retrospectively examined the medical records of 63 patients who received allo-HSCT and were administered tacrolimus. To compare bioavailability among different dose ranges, the blood concentration was divided by the dose (C/D). RESULTS: Thirty-nine patients (age range=children 1-15 years, adults 17-67 years) were switched to oral administration of tacrolimus. The C/D after switching was significantly lower in children than in adults (p=0.039). There was a strong positive correlation between age and C/D in children, whereas no correlation was observed in adults. CONCLUSION: In paediatric cancer patients, switching tacrolimus administration route may result in reduced blood concentrations. This tendency is more prominent in younger children.

Effects of Different Chromium Compounds on Hematology and Inflammatory Cytokines in Rats Fed High-Fat Diet.

The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.

Evaluation of an in vitro coronary stent thrombosis model for preclinical assessment.

Stent thrombosis remains an infrequent but significant complication following percutaneous coronary intervention. Preclinical models to rapidly screen and validate therapeutic compounds for efficacy are lacking. Herein, we describe a reproducible, high throughput and cost-effective method to evaluate candidate therapeutics and devices for either treatment or propensity to develop stent thrombosis in an in vitro bench-top model. Increasing degree of stent malapposition (0.00 mm, 0.10 mm, 0.25 mm and 0.50 mm) was associated with increasing thrombosis and luminal area occlusion (4.1 ± 0.5%, 6.3 ± 0.5%, 19.7 ± 4.5%, and 92.6 ± 7.4%, p < 0.0001, respectively). Differences in stent design in the form of bare-metal, drug-eluting, and bioresorbable vascular scaffolds demonstrated differences in stent thrombus burden (14.7 ± 3.8% vs. 20.5 ± 3.1% vs. 86.8 ± 5.3%, p < 0.01, respectively). Finally, thrombus burden was significantly reduced when healthy blood samples were incubated with Heparin, ASA/Ticagrelor (DAPT), and Heparin+DAPT compared to control (DMSO) at 4.1 ± 0.6%, 6.9 ± 1.7%, 4.5 ± 1.2%, and 12.1 ± 1.8%, respectively (p < 0.01). The reported model produces high throughput reproducible thrombosis results across a spectrum of antithrombotic agents, stent design, and degrees of apposition. Importantly, performance recapitulates clinical observations of antiplatelet/antithrombotic regimens as well as device and deployment characteristics. Accordingly, this model may serve as a screening tool for candidate therapies in preclinical evaluation.

Dynamic urinary metabolomics analysis based on UHPLC-Q-TOF/MS to investigate the potential biomarkers of blood stasis syndrome and the effects of Danggui Sini decoction.

Blood stasis syndrome (BSS) is one of the common syndromes in traditional Chinese medicine (TCM). It involves abnormal blood circulation, which can progress to produce many severe diseases. Danggui Sini decoction (DSD) is a classical TCM prescription frequently used to treat BSS by decreasing blood stasis and improving blood circulation. However, understanding of the therapeutic mechanism of DSD during the development of BSS is still limited, as the development of BSS is a slow dynamic process. Therefore, a dynamic urinary metabolomics analysis based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS) combined with multivariate statistical analysis was used to explore the distinctive metabolic patterns of BSS development and the efficacy of DSD. The dynamic changes of endogenous metabolites over time revealed the progression of BSS and allowed the overall efficacy of DSD in rats with BSS to be evaluated. The effects of the DSD compatibilities were also explored. A total of 21 metabolites were identified during the development of BSS. They are involved in the metabolic pathways of tryptophan metabolism, phenylalanine metabolism, riboflavin metabolism, nicotinate and nicotinamide metabolism, pentose and glucuronate interconversions, histidine metabolism, steroid hormone biosynthesis, and starch and sucrose metabolism. A receiver operating characteristic (ROC) curve analysis showed that 10 metabolites with an area under the curve (AUC) value >0.9, which can be used as potential biomarkers for the diagnosis of BSS. In conclusion, a dynamic urinary metabolomics approach was applied to identify potential biomarkers of the development of BSS and to clarify the therapeutic mechanism of DSD in BSS. The results could provide a theoretical basis for further research on the therapeutic mechanism of DSD.

Generation 2 (G2) - Generation 4 (G4) PAMAM dendrimers disrupt key plasma coagulation parameters.

The aim of the research was to evaluate the effects of G2 - G4 PAMAM dendrimers on basic plasma haemostasis parameters (Partially Activated Thrombin Time (APTT), Prothrombin Time (PT), Thrombin Time (TT)) as well as the activity of factor X, antithrombin III (AT), protein C and plasmin. Furthermore, tissue factor (TF) synthesis in endothelial cells and viability of smooth muscle cells in the presence of PAMAM dendrimers was investigated. APTT, PT and TT were performed according to the available commercial methods. The activity of factor X was conducted based on deficient plasma factor X. Protein C, AT and plasmin activity were measured spectrophotometrically using chromogenic substrates. Intracellular TF production in human umbilical vein endothelial cells (HUVECs) was measured using immunohistochemical method. Viability of Human Aortal Smooth Muscle cells (hAoSMCs) was established using WST-1 assay. PAMAM dendrimers decreased activity of factor X, and concomitantly prolonged PT and APTT. We also demonstrated shortened TT and increased fibrinogen concentrations in plasma treated with G4 PAMAM dendrimers, suggesting formation of fibrinogen aggregates. G2 - G4 PAMAM dendrimers decreased the activity of both naturally occurring anticoagulants AT and protein C. G2 and G3 PAMAM dendrimers did not affect the proteolytic reaction with plasmin. PAMAM dendrimers were found not to trigger TF production in undisturbed endothelial cells. PAMAM dendrimers, depending on the concentration and generation decreased viability of AoSMCs. The results presented within the current study suggest complex but mostly undesirable effect of G2 - G4 PAMAM dendrimers on plasma haemostasis and underscore the need for further in-depth research.

The effects of gold nanoparticles on the human blood functions.

The gold nanoparticles (AuNPs) have been widely used as drug delivery systems at several biomedical fields. However, the effect of AuNPs on the components of human blood is not well characterized. AuNPs firstly interacted with blood when using AuNPs as the drug delivery carries. Therefore, it is urgent to investigate the effect of AuNPs (including the ligands of AuNPs) on human blood, especially its components. In this study, we investigated the possible effects of polyethylene glycol-coated AuNPs (PEG@AuNPs) and citric acid-coated AuNPs (CT-AuNPs) on the blood cell function and distribution of those nanoparticles in blood components including erythrocytes, leukocytes, platelets (PLTs) cells and plasma. We found that the amount of CT-AuNPs engulfed by leukocytes was four folds more compared to PEG@AuNPs, indicating that PEGylation might have the ability to escape the immune system. We found that each individual leukocyte uptaked more AuNPs particles than individual platelet. However, there are more PLTs than leukocytes in the blood. The total amount of AuNPs including PEG@AuNPs and CT-AuNPs accumulation in PLTs were more than in leukocytes. Moreover, we found that both CT-AuNPs and PEG@AuNPs-induced PLTs activation at high concentration. We therefore concluded that the interactions between nanodrug delivery systems (AuNPs) and human blood components, especially the PLTs should be careful evaluated prior to their clinical applications.

The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review.

BACKGROUND: Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle. METHODS: A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy. RESULTS: Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1-4) was the most common event with prevalence ranging from 4-98%, followed by haematological (1.4-81%) and gastrointestinal (1.2-67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m2) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase. CONCLUSION: Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.

The evaluation of resorbable haemostatic wound dressings in contact with blood in vitro.

PURPOSE: For many years research has been conducted on the development of resorbable, polymer, haemostatic materials designed to provide first aid and preliminary protection of injuries. The biological properties in vitro of a dressing in powder form called Hemoguard are expected to provide the ability to instantaneously stem bleeding with safe conditions of use. The aim of the study was to evaluate the haemostatic properties of a model of dressing based on micro- and nanofibrids of the chitosan, sodium/calcium alginate and/or carboxymethylcellulose complex. Dressings were prepared by spray-drying and freeze-drying. METHODS: Human whole blood was subjected to timed contact with the haemostatic dressing model. Haemolytic action was determined by assaying the degree of haemolysis and evaluating blood cell morphology. Haemostatic action was determined on the basis of selected parameters of plasmatic clotting systems. RESULTS: Dressings prepared by freeze-drying activated the coagulation system. The haemolytic index, plasma haemoglobin concentration values and blood cell morphological shapes were normal. Dressings prepared by spray-drying significantly activated coagulation. Activation of the coagulation process was evidenced by shorter clotting time of the plasma coagulation system and a longer process of clot formation. The dressing was associated with an increased haemolytic index and higher plasma haemoglobin concentration. The morphological shape of blood cells changed. CONCLUSIONS: The model of multi-resorbable wound dressings has haemostatic properties. The materials activate the clotting process more quickly than a single-dressing model. Increased activity was found for dressings prepared by spray-drying.

Mechanical behavior and blood compatibility of copper-containing films as potential biomaterials.

Surface modification is one approach to enhance the biocompatibility of implanted cardiovascular devices. In this work, a copper-containing film used to blood contacted biomaterials was prepared by vacuum arc deposition. The phase composition of the films was investigated via X-ray diffraction, and the adherence strength of the films was evaluated with conventional deformation tests. Blood compatibility of the films was characterized by hemolysis ratio, clotting time and platelet adhesion etc. The surface of inferior vena cava filters were smooth and uniform, no cracks or delaminations were observed on the deformed surface. These results indicate that the mechanical behavior of the films is suitable for withstanding deformation stresses as operation in clinic. Good blood compatibility of the copper-containing films was identified through experiment in vitro, the activated partial thromboplastin times (APTTs) of Cu/Ti films were similar to that of the uncoated substrate, and Cu/Ti films were also found to inhibit platelet adhesion comparing to the nitinol substrate. However, with increasing ratio of Cu/Ti, the hemolysis ratio increased, resulting in platelet damage. These results indicate that the copper-containing film has potential application on blood contacted devices.

The consequence of biologic graft processing on blood interface biocompatibility and mechanics.

Processing ex vivo derived tissues to reduce immunogenicity is an effective approach to create biologically complex materials for vascular reconstruction. Due to the sensitivity of small diameter vascular grafts to occlusive events, the effect of graft processing on critical parameters for graft patency, such as peripheral cell adhesion and wall mechanics, requires detailed analysis. Isolated human umbilical vein sections were used as model allogenic vascular scaffolds that were processed with either: 1. sodium dodecyl sulfate (SDS), 2. ethanol/acetone (EtAc), or 3. glutaraldehyde (Glu). Changes in material mechanics were assessed via uniaxial tensile testing. Peripheral cell adhesion to the opaque grafting material was evaluated using an innovative flow chamber that allows direct observation of the blood-graft interface under physiological shear conditions. All treatments modified the grafts tensile strain and stiffness properties, with physiological modulus values decreasing from Glu 240±12 kPa to SDS 210±6 kPa and EtAc 140±3 kPa, P<.001. Relative to glutaraldehyde treatments, neutrophil adhesion to the decellularized grafts increased, with no statistical difference observed between SDS or EtAc treatments. Early platelet adhesion (% surface coverage) showed no statistical difference between the three treatments; however, quantification of platelet aggregates was significantly higher on SDS scaffolds compared to EtAc or Glu. Tissue processing strategies applied to the umbilical vein scaffold were shown to modify structural mechanics and cell adhesion properties, with the EtAc treatment reducing thrombotic events relative to SDS treated samples. This approach allows time and cost effective prescreening of clinically relevant grafting materials to assess initial cell reactivity.

Anticoagulant activity of some Artemisia dracunculus leaf extracts.

Platelet hyperactivity and platelet interaction with endothelial cells contribute to the development and progression of many cardiovascular diseases such as atherosclerosis and thrombosis. The impact of platelet activity with different pharmacological agents, such as acetylsalicylic acid and coumarin derivatives, has been shown to be effective in the prevention of cardiovascular disease. Artemisia dracunculus, L. Asteraceae (Tarragon) is used for centuries in the daily diet in many Middle Eastern countries, and it is well known for its anticoagulant activity. The present study investigates the presence of coumarins in tarragon leaves and subsequently determines the extract with a major amount of coumarin derivatives. The solvents of different polarities and different pH values were used for the purpose of purifying the primary extract in order to obtain fractions with the highest coumarin content. Those extracts and fractions were investigated for their anticoagulant activity by determining prothrombin time (PT) and the international normalized ratio (INR), expressed in relation to the coagulation time of the healthy person. Purified extracts and fractions obtained from plant residue after essential oil distillation, concentrated in coumarin derivatives, showed the best anticoagulant activity, using samples of human blood. INR maximum value (2.34) and consequently the best anticoagulant activity showed the methanol extract at concentration of 5%.  The INR value of normal plasma in testing this extract was 1.05.

Cell membrane-mimicking coating for blood-contacting polyurethanes.

The aim of the present work was to develop simple modification technique for polyurethanes (PUs) intended for use in blood-contacting implants (vascular grafts, heart prosthesis, ventricular assist devices). PU surface was modified with soybean-derived phosphatidylcholine (PC) via one-step dip coating technique. In order to evaluate blood compatibility of the obtained materials, samples were contacted with human blood under static and arterial flow-simulated conditions. The PC-modified surfaces were thoroughly characterized and tested for fibrinogen resistance, the ability to resist platelet adhesion and activation, hemolysis percentage and plasma recalcification time. Results demonstrated significant, more than three-fold reduction in the amount of fibrinogen adsorbed to PC-modified materials as compared to non-modified PU. Analysis of the samples' surface after incubation with blood showed high reduction in platelet adhesion. The results were confirmed by analysis of blood samples collected after shear-stress tests--the percentage of free (non-aggregated) platelets remaining in blood samples contacted with PC-coated materials exceeded 70%. The same parameter measured for non-modified PU was significantly lower and equaled 28%.

Monitoring the toxic effects of Pb, Cd and Cu on hematological parameters of Wistar rats and potential protective role of lipoic acid and glutathione.

Heavy metal pollution is a serious environmental and health problem. The negative effects of heavy metals that can enter human body can be reduced by the addition of some supplements. In this study, the effects of lead (Pb), cadmium (Cd) and copper (Cu) on the hematological parameters in Wistar rats in the absence and presence of lipoic acid and glutathione were analyzed. Pb, Cd and Cu intoxication significantly affected the hematological parameters of treated animals. The main effects in the case of Pb and Cd intoxication were decreased values of erythrocytes, hemoglobin and hematocrit (up to 30% and 20% for these two metals, respectively) compared with the control group. Cu intoxication caused decrease in hematocrit, thrombocytes, mean cell volume values (c.a. 15%) and slight decrease in the erythrocyte number, while the value of hemoglobin increased (c.a. 7%). The treatment with lipoic acid and glutathione reduced the toxic effects of these metals in all cases.

Hemocompatibility testing according to ISO 10993-4: discrimination between pyrogen- and device-induced hemostatic activation.

Next to good hemocompatibility performance of new medical devices, which has to be tested according to the ISO 10993-4, the detection of pyrogen-contaminated devices plays a pivotal role for safe device application. During blood contact with pyrogen-contaminated devices, intense inflammatory and hemostatic reactions are feared. The aim of our study was to investigate the influence of pyrogenic contaminations on stents according to the ISO 10993-4. The pyrogens of different origins like lipopolysaccharides (LPS), purified lipoteichoic acid (LTA) or zymosan were used. These pyrogens were dried on stents or dissolved and circulated in a Chandler-loop model for 90 min at 37°C with human blood. Before and after circulation, parameters of the hemostatic system including coagulation, platelets, complement and leukocyte activation were investigated. The complement system was activated by LPS isolated from Klebsiella pneumoniae and Pseudomonas aeruginosa and by LTA. Leukocyte activation was triggered by LPS isolated from K. pneumoniae, LTA and zymosan, whereas coagulation and platelet activation were only slightly influenced. Our data indicate that pyrogen-contaminated devices lead to an alteration in the hemostatic response when compared to depyrogenized devices. Therefore, pyrogenicity testing should be performed prior to hemocompatibility tests according to ISO 10993-4 in order to exclude hemostatic activation induced by pyrogen contaminations.

The effects of the antiplatelet agents, aspirin and naproxen, on pharmacokinetics and pharmacodynamics of the anticoagulant edoxaban, a direct factor Xa inhibitor.

Edoxaban is an oral factor Xa (FXa) inhibitor in clinical development for stroke prevention in patients with atrial fibrillation, an elderly population that frequently receives aspirin (ASA) and/or nonsteroidal anti-inflammatory drugs for concurrent illnesses. Three studies were conducted to evaluate the pharmacokinetic and pharmacodynamic interactions of edoxaban 60 mg coadministered with low-dose (100 mg) ASA, high-dose (325 mg) ASA, or naproxen (500 mg) in healthy subjects (n = 126). Template bleeding times (BT) were measured. Mean baseline (predose) BT for the 3 studies ranged from 4.72 to 6.13 minutes. Edoxaban administered alone increased BT by 21%-35% (4 hours post dose) from baseline. Concomitant administration of edoxaban with high-dose ASA, low-dose ASA, or naproxen increased BT approximately 2-fold showing an additive effect greater than either agent administered alone. Edoxaban pharmacokinetics were not affected by concomitant low-dose ASA or naproxen, but high-dose ASA increased systemic exposure of edoxaban by approximately 30%. The effects of edoxaban on prothrombin time, activated partial thromboplastin time, international normalized ratio, anti-FXa, and intrinsic FXa activity were not influenced by administration with ASA or naproxen. Inhibition of platelet aggregation by high-dose ASA, low-dose ASA, or naproxen was not affected by edoxaban. Concomitant administration of edoxaban and ASA or naproxen was well tolerated.

Blood gases and energy metabolites in mouse blood before and after cerebral ischemia: the effects of anesthetics.

The levels of blood gases and energy metabolites strongly influence the outcome of animal experiments, for example in experimental stroke research. While mice have become prominent animal models for cerebral ischemia, little information is available on the effects of anesthetic drugs on blood parameters such as blood gases, glucose and lactate in this species. In this work, we collected arterial and venous blood samples from female CD-1 mice before and after cerebral ischemia induced by middle cerebral artery occlusion (MCAO), and we tested the influence of different anesthetic drugs. We found that all of the injectable anesthetics tested (ketamine/xylazine, chloral hydrate, propofol and pentobarbital) caused a decrease in blood pH and partial pressure of oxygen (pO2) and an increase of partial pressure of carbon dioxide (pCO2), indicating respiratory depression. This was not observed with inhalable anesthetics such as isoflurane, sevoflurane and halothane. Significant and up to two-fold increases of blood glucose concentration were observed under isoflurane, halothane, ketamine/xylazine, chloral hydrate, and propofol anesthesia. Lactate concentration rose significantly by 2-3-fold during inhalation of isoflurane and halothane treatment, but decreased by more than 50% after administration of pentobarbital. Permanent cerebral ischemia induced respiratory acidosis (low pH and pO2, high pCO2) which was most prominent after 24 h. Postsurgical treatment with Ringer-lactate solution (1 mL, intraperitoneal) caused a recovery of blood gases to basal levels after 24 h. Use of isoflurane for surgery caused a minor increase of blood glucose concentrations after one hour, but a strong increase of blood lactate. In contrast, anesthesia with pentobarbital did not affect glucose concentration but strongly reduced blood lactate concentrations one hour after surgery. All values recovered at three hours after MCAO. In conclusion, anesthetic drugs have a strong influence on murine blood parameters, which should be taken into account in experiments in mice.

Hemocompatibility evaluation of different silver nanoparticle concentrations employing a modified Chandler-loop in vitro assay on human blood.

Due to their antibacterial effects, the use of silver nanoparticles (AgNPs) in a great variety of medical applications like coatings of medical devices has increased markedly in the last few years. However, blood in contact with AgNPs may induce adverse effects, thereby altering hemostatic functions. The objective of this study was to investigate the hemocompatibility of AgNPs in whole blood. Human whole blood (n=6) was treated with different AgNPs concentrations (1, 3 and 30mgl(-1)) or with saline/blank solutions as controls before being circulated in an in vitro Chandler-loop model for 60min at 37°C. Before and after circulation, various hematologic markers were investigated. Based on the hematologic parameters measured, no profound changes were observed in the groups treated with AgNP concentrations of 1 or 3mgl(-1). AgNP concentrations of 30mgl(-1) induced hemolysis of erythrocytes and α-granule secretion in platelets, increased CD11b expression on granulocytes, increased coagulation markers thrombin-antithrombin-III complex, kallikrein-like and FXIIa-like activities as well as complementing cascade activation. Overall, we provide for the first time a comprehensive evaluation including all hematologic parameters required to reliably assess the hemocompatibility of AgNPs. We strongly recommend integrating these hemocompatibility tests to preclinical test procedures prior to in vivo application of new AgNP-based therapies.

In vitro assessment of blood compatibility: residual and dynamic markers of cellular activation.

The blood compatibility of materials and surfaces used for medical device fabrication is a crucial factor in their function and effectiveness. Expansion of device use into more sensitive and longer term applications warrants increasingly detailed evaluations of blood compatibility that reach beyond the customary measures mandated by regulatory requirements. A panel of tests that assess both deposition on the surface and activation of circulating blood in contact with the surface has been developed. Specifically, the ability of a surface to modulate the biological response of blood is assessed by measuring: (1) dynamic thrombin generation; (2) surface-bound thrombin activity after exposure to blood; (3) activation of monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets; (4) activation of complement; and (5) adherent monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets on blood-contacting surfaces. The tests were used to evaluate surfaces modified with immobilized heparin (Ension's proprietary bioactive surface) and demonstrated that the modified surfaces reduced platelet activation, leukocyte activation, and complement activation in flowing human blood. Perfusion of the surfaces with human platelet-rich plasma showed that the immobilized heparin surfaces also reduce both dynamic thrombin levels in the circulating plasma and residual thrombin generated at the material surface.

The effects of lactated Ringer's solution (LRS) or LRS and 6% hetastarch on the colloid osmotic pressure, total protein and osmolality in healthy horses under general anesthesia.

OBJECTIVE: To investigate changes in colloid osmotic pressure (COP), total protein (TP) and osmolality (OSM) during anesthesia in horses given intravenous lactated Ringer's solution (LRS) or LRS and hetastarch (HES). STUDY DESIGN: Prospective, clinical trial. ANIMALS: Fourteen horses presented for surgery. Mean age 8.3 ± 1.9 years; mean weight 452 ± 25 kg. METHODS: Horses were premedicated with xylazine intravenously (IV); anesthesia was induced with ketamine and diazepam IV, and maintained with sevoflurane. Butorphanol was administered IV with pre-medications or immediately after induction. Xylazine was administered IV for recovery if necessary. LRS was administered IV to all horses with a target rate of 5-10 mL kg(-1) hour(-1). Half of the horses also received 6% HES, 2.5 mL kg(-1) over 1 hour in addition to LRS. Horses that received LRS only were considered the LRS group. Horses that received both LRS and HES were considered the LRS/HES group. Blood was drawn pre- and post-anesthesia, immediately following induction, and every 30 minutes throughout anesthesia. COP, TP and OSM were measured. RESULTS: COP and TP significantly decreased at similar rates for both treatment groups from pre-anesthetic values. Pre-anesthetic COP was significantly greater in the LRS group when compared to the LRS/HES group pre-, post- and throughout anesthesia. In the LRS group post-anesthetic OSM was significantly different than the pre-anesthesia value and that for the LRS/HES group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of IV HES (2.5 mL kg(-1), over 1 hour) in combination with LRS does not attenuate the decrease in COP typically seen during anesthesia with crystalloid administration alone. Based on these results, administration of HES at this rate and total volume would not be expected to prevent fluid shifts into the interstitium through its effects on COP.

Menstrual blood loss measurement: validation of the alkaline hematin technique for feminine hygiene products containing superabsorbent polymers.

OBJECTIVE: To validate the alkaline hematin technique for measurement of menstrual blood loss using ultra-thin sanitary towels that contain superabsorbent polymer granules as the absorptive agent. DESIGN: Laboratory study using simulated menstrual fluid (SMF) and Always Ultra Normal, Long, and Night "with wings" sanitary towels. SETTING: Keele Menstrual Disorders Laboratory. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Recovery of blood, linearity, and interassay variation over a range of SMF volumes applied to towels. Because of the variable percentage of blood in menstrual fluid, blood recovery was assessed from SMF constituted as 10%, 25%, 50%, and 100% blood. The lower limit of reliable detection and the effect of storing soiled towels for up to 4 weeks at 15°C-20°C, 4°C, and -20°C before analysis were determined. RESULT(S): Ninety percent recovery was reproducibly achieved up to 30 mL applied volume at all tested SMF compositions, except at low volume or high dilution equivalent to <2 mL whole blood. Samples could be stored for 3 weeks at all tested temperatures without loss of recovery. The technique was suitable for processing towels individually or in batches. CONCLUSION(S): The alkaline hematin technique is a suitable and validated method for measuring menstrual blood loss from Always Ultra sanitary towels that contain superabsorbent polymers.