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Many emerging technologies are reliant on circulating cell-free DNA (cfDNA) and cell-free RNA (cfRNA) applications in the clinic. However, the impact of diurnal cycles or daily meals on circulating analytes are poorly understood and may be confounding factors when developing diagnostic platforms. To begin addressing this knowledge gap, we obtained plasma from four healthy donors serially sampled five times during 12 h in a single day. For all samples, we measured concentrations of cfDNA and cfRNA using both bulk measurements and gene-specific digital droplet PCR. We found no significant variation attributed to blood draw number for the cfDNA or cfRNA. This indicated that natural diurnal cycles and meal consumption do not appear to significantly affect abundance of total cfDNA, total cfRNA, or our two selected cfRNA transcripts. Conversely, we observed significant variation between individual donors for cfDNA and one of the cfRNA transcripts. The results of this work suggest that it will be important to consider patient-specific baselines when designing reliable circulating cfDNA or cfRNA clinical assays.

Piperacillin is considered a moderately protein-bound antibiotic (20%-40%), with albumin being an important binding protein. Although infrequently used in practice, different methods to measure the fraction unbound (fu) are available, but uncertainty remains as to what the most appropriate method is. The main goal of this study was to estimate the impact of the methodology used to measure unbound piperacillin in plasma on the fu of piperacillin; we compared ultrafiltration (UF) at 4°C and 37°C with the reference method, equilibrium dialysis. In addition, we analyzed the impact of other proteins on the fu.Anonymized left-over Li-heparin plasma samples (n = 41) from 30 critically ill patients who were treated with piperacillin were used for the analyses.We found that the piperacillin fu, determined by UF, is on average 8% higher at 37°C (91%) than at 4°C (83%). There were no systematic or proportional differences between UF at 4°C and equilibrium dialysis at 4°C. This emphasizes the importance of the temperature during UF, which should therefore be clearly stated in publications that report on the methodology of UF. No significant impact of the albumin-, IgA-, total protein-, or α1-acid glycoprotein concentration on the fu was found. The fu found in this study was higher than the generally assumed fu value of 60%-80%. A possible explanation lies in the studied population or in the temperature used. Based on our results, routine monitoring of unbound piperacillin in intensive care unit patients is not recommended.Based on the prediction model, we can state that in intensive care patients the fu of piperacillin is 91% (SD 7%), determined with UF at 37°C.

Lipidomics – the global assessment of lipids – can be performed using a variety of mass spectrometry (MS)-based approaches. However, choosing the optimal approach in terms of lipid coverage, robustness and throughput can be a challenging task. Here, we compare a novel targeted quantitative lipidomics platform known as the Lipidyzer to a conventional untargeted liquid chromatography (LC)-MS approach. We find that both platforms are efficient in profiling more than 300 lipids across 11 lipid classes in mouse plasma with precision and accuracy below 20% for most lipids. While the untargeted and targeted platforms detect similar numbers of lipids, the former identifies a broader range of lipid classes and can unambiguously identify all three fatty acids in triacylglycerols (TAG). Quantitative measurements from both approaches exhibit a median correlation coefficient (r) of 0.99 using a dilution series of deuterated internal standards and 0.71 using endogenous plasma lipids in the context of aging. Application of both platforms to plasma from aging mouse reveals similar changes in total lipid levels across all major lipid classes and in specific lipid species. Interestingly, TAG is the lipid class that exhibits the most changes with age, suggesting that TAG metabolism is particularly sensitive to the aging process in mice. Collectively, our data show that the Lipidyzer platform provides comprehensive profiling of the most prevalent lipids in plasma in a simple and automated manner.

To identify determinants of long-term implant survival after sinus augmentation procedure (SAP) using a combination of plasma rich in growth factors (PRGF) and graft material.Patients were included in this retrospective study if they underwent SAP through a lateral wall approach using PRGF in combination with mainly xenograft, and received implants restored for at least 1 year. Sociodemographic, behavioral and implant characteristics (clinical factors, implant details, surgical details, prosthesis details, and complications) were analyzed.Sixty-seven patients received 217 implants in 100 augmented sinuses. The mean follow-up was 7.2 years. Overall, 22 implants failed in 15 patients (90% cumulative implant survival). Multivariable models showed greater implant survival with implants placed with ≥5 mm of residual crestal bone height (RBH) compared with those placed with3 mm of RBH. There was also an improvement in survival comparing implant lengths. In addition, immediate loading of implants significantly increased the risk of implant failure.The use of PRGFs for maxillary sinus grafting may be an effective and safe treatment option for the rehabilitation of atrophic edentulous posterior maxillae. However, randomized clinical trials are needed to confirm these findings.

Background: The progression of systemic lupus erythematosus (SLE) leads to anemia in patients, adversely affecting prognosis. The diverse causes of anemia may include excessive eryptosis or premature suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine (PS) exposure on the cell surface. The present study explored if SLE enhances eryptosis and the underlying mechanisms. Materials and Methods: Eryptosis was assessed using flow cytometry in healthy volunteers (n = 20) and anemic patients hospitalized for SLE (n = 22), for parameters including PS exposure, cell volume, cytosolic calcium ion (Ca2+) levels and reactive oxygen species (ROS) and ceramide abundance. These indicators were measured in erythrocytes of experimental subjects and erythrocytes treated with plasma from healthy volunteers or SLE patients. Results: The hemoglobin and hematocrit levels were significantly lower in anemic SLE patients than in healthy volunteers (***p

Bleeding is a serious complication after pediatric cardiopulmonary bypass (CPB) that is associated with an increase in perioperative morbidity and mortality. Four-factor prothrombin complex concentrates (4F-PCCs) have been used off-label to supplement transfusion protocols for bleeding after CPB in adults; however, data on their use in neonates are limited. In this study, we hypothesized that 4F-PCCs administered ex vivo to neonatal plasma after CPB will increase thrombin generation.Fifteen neonates undergoing complex cardiac repairs requiring CPB were enrolled in this prospective study. Arterial blood was obtained after anesthesia induction but before CPB (baseline), after CPB following heparin reversal, and after our standardized transfusion of a quarter of a platelet apheresis unit (approximately 20 mL·kg) and 3 units of cryoprecipitate. Kcentra (CSL Behring), a 4F-PCC with nonactivated factor VII (FVII), and factor 8 inhibitor bypassing activity (FEIBA; Baxter Healthcare Corporation), a 4F-PCC with activated FVII, were added ex vivo to plasma obtained after CPB to yield concentrations of 0.1 and 0.3 IU·mL. Calibrated automated thrombography was used to determine thrombin generation for each sample.The addition of Kcentra to plasma obtained after CPB resulted in a dose-dependent increase in the median (99% confidence interval) peak amount of thrombin generation (42.0 [28.7-50.7] nM for Kcentra 0.1 IU·mL and 113.9 [99.0-142.1] nM for Kcentra 0.3 IU·mL). The rate of thrombin generation was also increased (15.4 [6.5-24.6] nM·min for Kcentra 0.1 IU·mL and 48.6 [29.9-66.6] nM·min for Kcentra 0.3 IU·mL). The same was true for FEIBA (increase in peak: 39.8 [27.5-49.2] nM for FEIBA 0.1 IU·mL and 104.6 [92.7-124.4] nM for FEIBA 0.3 IU·mL; increase in rate: 17.4 [7.4-28.8] nM·min FEIBA 0.1 IU·mL and 50.5 [26.7- 63.1] nM·min FEIBA 0.3 IU·mL). In the posttransfusion samples, there was a significant increase with Kcentra in the median (99% confidence interval) peak amount (41.1 [21.0-59.7] nM for Kcentra 0.1 IU·mL and 126.8 [106.6- 137.9] nM for Kcentra 0.3 IU·mL) and rate (18.1 [-6.2 to 29.2] nM·min for Kcentra 0.1 IU·mL and 53.2 [28.2-83.1] nM·min for Kcentra 0.3 IU·mL) of thrombin generation. Again, the results were similar for FEIBA (increase in peak: 43.0 [36.4-56.7] nM for FEIBA 0.1 IU·mL and 109.2 [90.3-136.1] nM for FEIBA 0.3 IU·mL; increase in rate: 25.0 [9.1-32.6] nM·min for FEIBA 0.1 IU·mL and 59.7 [38.5-68.7] nM·min for FEIBA 0.3 IU·mL). However, FEIBA produced in a greater median reduction in lag time of thrombin generation versus Kcentra in samples obtained after CPB (P = 0.003 and P = 0.0002 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL, respectively) and in samples obtained after transfusion (P0.0001 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL).After CPB, thrombin generation in neonatal plasma was augmented by the addition of 4F-PCCs. The peak amount and rate of thrombin generation were enhanced in all conditions, whereas the lag time was shortened more with FEIBA. Our findings suggest that the use of 4F-PCCs containing activated FVII may be an effective adjunct to the initial transfusion of platelets and cryoprecipitate to augment coagulation and control bleeding in neonates after CPB.

Background Plasma and serum are often used interchangeably for therapeutic drug monitoring (TDM) purposes, and concentrations of some drugs are reported to be lower in serum than in plasma when collected into blood collection tubes containing a gel separator. TDM is recommended for clozapine, although few studies have compared concentrations between plasma and serum. Therefore, we investigated the comparability of dipotassium ethylenediaminetetraacetic acid human plasma and serum from blood collection tubes containing a gel separator for the measurement of clozapine and norclozapine. Methods Whole blood from patients (N = 93) prescribed clozapine was collected into a polypropylene Vacuette dipotassium ethylenediaminetetraacetic acid-containing blood collection tube (Greiner Bio-One), and a polypropylene Vacuette serum separator blood collection tube (Greiner Bio-One) containing a clotting activator (silica particles) and a polymer gel. Results Mean clozapine concentrations were significantly (P ≤ 0.05) lower in serum (0.37 mg/L) than in plasma (0.39 mg/L), as were concentrations of norclozapine (0.17 and 0.18 mg/L, respectively). Bland-Altman plots indicated mean serum clozapine and norclozapine were 0.018 mg/L (5.3%) and 0.004 mg/L (3.6%), respectively, lower in serum than plasma. Conclusions Despite the finding that clozapine and norclozapine were significantly higher in plasma than in serum when obtained from blood collected into Vacuette serum separator collection tubes, this difference is insignificant in the clinical interpretation of clozapine and norclozapine TDM results.

Hemolysis can occur as a consequence of extracorporeal membrane oxygenation (ECMO) and is associated with increased mortality and morbidity. Shear stress generated by flow through the circuit and oxygenator is believed to cause ECMO-induced hemolysis. We hypothesize that either a smaller dimension oxygenator or an in-line hemofilter will increase ECMO-associated hemolysis. Circuits were configured with a Quadrox-D Adult oxygenator (surface area 1.8 m), Quadrox-iD Pediatric oxygenator (surface area 0.8 m), or Quadrox-D Adult oxygenator with an in-line hemofilter (N = 4) and ran for 6 hours. Samples were collected hourly from the ECMO circuit and a time-based hemolysis control. Plasma hemoglobin levels were assayed. Circuit-induced hemolysis at each time point was defined as the change in plasma hemoglobin standardized to the time-based hemolysis control. Plasma hemoglobin increased with the use of the smaller dimension pediatric oxygenator as compared with the adult oxygenator when controlling for ECMO run time (p = 0.02). Furthermore, there was a greater pressure gradient with the smaller dimension pediatric oxygenator (p < 0.05). Plasma hemoglobin did not change with the addition of the in-line hemofilter. The use of a smaller dimension pediatric oxygenator resulted in greater hemolysis and a higher pressure gradient. This may indicate that the increased shear forces augment ECMO-induced hemolysis.

This review considers the causes and consequences of an abnormal plasma sodium concentration and offers a framework for correcting it.

A total of sixteen lambs were divided into two groups and fed two different diets. Of these, eight lambs were fed a control diet (C) and eight lambs were fed the C diet supplemented with quebracho tannins (C+T). The objective of the present study was to assess whether dietary quebracho tannins can improve the antioxidant capacity of lamb liver and plasma and if such improvement is due to a direct transfer of phenolic compounds or their metabolites, to the animal tissues. Feed, liver and plasma samples were purified by solid-phase extraction (SPE) and analysed by liquid chromatography–MS for phenolic compounds. Profisitinidin compounds were identified in the C+T diet. However, no phenolic compounds were found in lamb tissues. The liver and the plasma from lambs fed the C+T diet displayed a greater antioxidant capacity than tissues from lambs fed the C diet, but only when samples were not purified with SPE. Profisetinidin tannins from quebracho seem not to be degraded or absorbed in the gastrointestinal tract. However, they induced antioxidant effects in animal tissues.

Transthyretin amyloid cardiomyopathy (ATTR cam) is likely an under-recognized cause of heart failure (HF) in the elderly [1], owing to misattribution of clinical features to other common co-morbidi...

Introduction We previously reported that a combination of factors VIIa (FVIIa) and X (FX) might represent an effective and attractive alternative to recombinant factor VIIa (rFVIIa) and plasma-derived activated prothrombin complex concentrate (APCC) for controlling bleeding in hemophiliacs with inhibitors. The present study describes the standardization and preparation of a virus-inactivated and nano-filtrated plasma-derived FVIIa/FX concentrate. We hypothesized that the hemostatic capacity was equivalent to or better than current bypassing agents as evaluated by measurements of waveform APTT clotting and thrombin generation. Results Kinetic analyses showed that a "normal" FX concentration of approximately 140 nM in plasma did not induce maximum catalytic efficacy of FVIIa and that an increase in the concentration of FX in hemophilic plasma enhanced the thrombin generation potential of FVIIa. Thus, the FVIIa/FX mixture was prepared by assembling plasma-derived FVIIa and FX at a weight ratio of 1:10. The FVIIa/FX mixture proved superior to rFVIIa with regards to shortening the APTT and accelerating the thrombin generation in hemophilic plasma. The FVIIa/FX mixture promoted the generation of thrombin more than did rFVIIa. Conclusions Increasing the FX concentration in hemophilic plasma gives a higher clotting potential of FVIIa. A FVIIa/FX concentrate may serve as a new alternative bypassing agent.

BACKGROUND: The manufacture of fresh-frozen plasma (FFP) requires that plasma be frozen within 8 hours of collection and 24-hour frozen plasma requires 1 to 6°C refrigeration before freezing. Manufacture of plasma after a room temperature hold for 24 hours, while convenient, could compromise clotting factor levels. STUDY DESIGN AND METHODS: Pairs of FFP and 24-hour room temperature–frozen plasma (PLT-rich plasma [PRP]-24HRTFP) were manufactured from PRP after a room temperature hold for 8 and 24 hours, respectively. Additional whole blood (WB) donations were kept at room temperature for 24 hours before plasma manufacture (WB-24HRTFP). The frozen plasma products were stored at −18°C, thawed, and then stored at 1 to 6°C, with coagulation factor assays performed for up to 7 days. RESULTS: On the day of thaw, Factor (F)VIII was lower in PRP-24HRTFP by 13% (p = 0.002) but not in WB-24HRTFP (p = 0.3) compared to FFP. All other clotting factors were within normal range. During the postthaw period FVIII and FV declined 25 and 6%, respectively, in WB-24HRTFP and 23 to 50% in the paired products; however, the difference between both types of 24HRTFP and FFP is insignificant by Day 7 (p > 0.05). Other clotting factors either were unchanged or showed minimal reduction (

To identify peripheral lymphovenous communications (LVCs) using labelled erythrocytes and intradermal injection. Intradermal injection delivers macromolecules to loco-regional lymph nodes faster than subcutaneous injection, suggesting easier lymphatic vessel access.Autologous erythrocytes labelled with 111In and 99mTc were injected into opposite hands. In four normal volunteers, the differentially labelled cells were given by intradermal injection on one side and subcutaneous injection on the other while in four breast cancer patients they were given by intradermal injection bilaterally 3 months after axillary lymph node clearance surgery. The axillae were imaged and blood samples obtained bilaterally at approximately 15, 30, 60, 120 and 180 min post-injection. Plasma activity was subtracted from whole blood activity to obtain erythrocyte-bound activity and contralateral concentrations were subtracted from ipsilateral concentrations to correct for ipsilateral recirculation. From estimated blood volume, erythrocyte and plasma activities contralateral to the injected side were calculated as percentage administered activity. Tracer concentrations in ipsilateral samples (%/l) were integrated to give total percentage administered activity, assuming a forearm blood flow of 20 ml/min.Kinetics of plasma activity were consistent with small diffusible 99mTc complexes and protein-bound 111In. With both radionuclides, axillary nodes were visualized after intradermal but not subcutaneous injection, suggesting that nodal activity arises from erythrocytes. In one patient, 99mTc and 111In labelled erythrocytes accumulated in similar amounts ipsilaterally and contralaterally, suggesting bilateral LVCs distal to the ipsilateral sampling point. There was no evidence of LVCs in the other seven volunteers.Intradermally injected erythrocytes are able to detect and potentially quantify peripheral LVCs.

Background A possible strategy to prolong plasma metabolism of Levodopa/Carbidopa (LD/CD) is Entacapone addition (EN), which improves impaired motor behaviour in patients with Parkinson’s disease (PD). Aims of the study Objectives were to evaluate the clinical response to an increased dopaminergic substitution with EN by clinical rating and assessment of complex motions and to investigate the change of movement in PD patients during repeat drug administration during an eight hour interval. Methods We used peg insertion with a computer based device and clinical rating for assessment of motor function in 20 treated PD patients. They received LD/CD and then the same LD/CD dosage plus EN in a standardised, open label fashion. Results Motor scores and performance of the instrumental task were significantly better and the fluctuation of movement was less intense during the LD/CD/EN condition according to the motor test outcomes. Conclusion EN supplementation improves motor symptoms and provides a more continuous movement behaviour in PD patients.

trans-Sodium crocetinate (TSC) increases the diffusion coefficient of glucose through water by about 25-30%. This is the same percentage increase that TSC causes in the diffusivity of oxygen through water. TSC is also found to induce order in the surrounding water structure through increased hydrogen bonding of the water molecules, and molecular simulations suggest that the increase in diffusivity occurs only in these ordered regions.

Autohydrolysis of blood factor XII (FXII+FXIIa-->2FXIIa) is found to be a facile reaction in neat-buffer buffer solutions of FXII but an insignificant reaction in the presence of plasma proteins. Autohydrolysis causes a chromogenic assay for FXIIa in buffer solution to strongly deviate from the traditional plasma-coagulation assay. Autohydrolysis can be accommodated by performing chromogenic detection of FXIIa as a rate assay in swamping concentrations of FXII. Rate-assay results performed in this way are shown to be in analytical agreement with the plasma-coagulation assay. Autohydrolysis can be used as a means of amplifying FXIIa produced by contacting neat-buffer solutions of FXII with biomaterials, suggesting a route to highly sensitive measurement of biomaterial hemocompatibility.

The strong ion approach provides a quantitative physicochemical method for describing the mechanism for an acid-base disturbance. The approach requires species-specific values for the total concentration of plasma nonvolatile buffers (Atot) and the effective dissociation constant for plasma nonvolatile buffers ( Ka), but these values have not been determined for human plasma. Accordingly, the purpose of this study was to calculate accurate Atotand Kavalues using data obtained from in vitro strong ion titration and CO2tonometry. The calculated values for Atot(24.1 mmol/l) and Ka(1.05 × 10−7) were significantly ( P < 0.05) different from the experimentally determined values for horse plasma and differed from the empirically assumed values for human plasma (Atot= 19.0 meq/l and Ka= 3.0 × 10−7). The derivatives of pH with respect to the three independent variables [strong ion difference (SID), Pco2, and Atot] of the strong ion approach were calculated as follows: [Formula: see text] [Formula: see text], [Formula: see text]where S is solubility of CO2in plasma. The derivatives provide a useful method for calculating the effect of independent changes in SID+, Pco2, and Atoton plasma pH. The calculated values for Atotand Kashould facilitate application of the strong ion approach to acid-base disturbances in humans.

To assess rate of biophase recovery, the recovery from neuromuscular block with mivacurium in the isolated forearm was compared with that from vecuronium simultaneously administered into the other isolated forearm of six volunteers. In a second series of similar experiments, recovery from doxacurium was compared with that from vecuronium. Neuromuscular block was monitored using the adductor pollicis mechanomyographic response to ulnar nerve stimulation at 0.2 Hz. Comparable degrees of maximum twitch tension depression were obtained in each series. In the first series, mean (SD) 25-75% recovery index for mivacurium was 8.4 (1.5) min and 10.5 (1.9) min for vecuronium. In the second series, mean (SD) recovery index for doxacurium was 18.3 (4.2) min and 12.2 (5.0) min for vecuronium. The recovery index of doxacurium in the isolated forearm was significantly greater, and the recovery index of mivacurium significantly less, than the recovery index of simultaneously administered vecuronium. Mivacurium block in the isolated forearm recovers rapidly, although not faster than after systemic injection; this is consistent with a drug that is retained in the biophase despite rapid plasma metabolism. Doxacurium block in the isolated forearm is slow to recover, compared with vecuronium; this suggests that high affinity for the biophase may contribute to its long duration of action.

Effect of diet on plasma acid-base composition in normal humans. Steady-state plasma and urine acid-base composition was assessed in 19 studies of 16 normal subjects who ingested constant amounts of one of three diets that resulted in different rates of endogenous noncarbonic acid production (EAP) within the normal range. Renal net acid excretion (NAE) was used to quantify EAP since the two variables are positively correlated in normal subjects. A significant positive correlation was observed between plasma [H+] and plasma PCO2, and between plasma [HCO3-] and plasma PCO2, among the subjects. Multiple correlation analysis revealed a significant interrelationship among plasma [H+], plasma PCO2, and NAE (r = 0.71, P < 0.001), and among plasma [HCO3-], plasma PCO2, and NAE (r = 0.77, P < 0.001). The partial correlation coefficients indicated a significant positive correlation between plasma [H+] and NAE, and a significant negative correlation between plasma [HCO3-] and NAE, when plasma PCO2 was held constant. These findings indicate that two factors influence the level at which plasma [H+] is maintained in normal subjects: (1) the steadystate rate of endogenous noncarbonic acid production, and (2) the setpoint at which plasma PCO2 is regulated by the respiratory system. Plasma [HCO3-] is also co-determined by these two factors. In disease states, therefore, both factors must be known before a disturbance in acid-base homeostasis can be excluded.Effet du régime sur la composition acido-basique plasmatique chez des sujets humains normaux. La composition acido-basique plasmatique et urinaire à l'équilibre a été déterminée dans 19 études de 16 sujets normaux qui ingéraient des quantités constantes de l'un de trois régimes aboutissant à différents taux de production endogène d'acides non carboniques (EAP) à l'intérieur de la normale. L'excrétion rénale nette d'acides (NAE) a été utilisée pour quantifier l'EAP puisque les deux variables sont positivement corrélées chez des sujets normaux. Une corrélation significative positive a été observée entre le [H+] plasmatique et la PCO2 plasmatique, et entre le [HCO3-] plasmatique et PCO2 plasmatique, parmi ces sujets. Une analyse par corrélations multiples a révélé une interrelation significative entre [H+] plasmatique, PCO2 plasmatique et NAE (r = 0,71, P < 0,001), et entre [HCO3-] plasmatique, PCO2 plasmatique et NAE (r = 0,77, P < 0,001). Les coefficients de corrélation partielle ont indiqué une corrélation significative positive entre [H+] plasmatique et NAE, et une corrélation significative négative entre [HCO3-] plasmatique et NAE, lorsque PCO2 plasmatique était maintenue constante. Ces résultats indiquent que deux facteurs influencent le niveau auqeal [H+] plasmatique est maintenu chez des sujets normaux: (1) le taux de production à l'équilibre d'acides non carboniques endogènes, et (2) le point d'équilibre auquel PCO2 plasmatique est régulée par le système respiratoire. [HCO3-] plasmatique est également codéterminé par ces deux facteurs. Ainsi, dans les états pathologiques, les deux facteurs doivent être connus avant de pouvoir exclure une perturbation de l'homéostasie acido-basique.

Rats injected with labelled fibrinogen were subjected to a standardized, third degreethermal injury and sacrificed at various intervals after the burn for radioactivity measurement of blood and organ samples. 5 min post-barn a moderate elevation of the lung radioactivity was found, and this elevation could be prevented by previous heparinization, indicating that the increase was a result offibrin deposition in the lungs.

SummaryThe ultrafiltration technique was employed to measure the extent of 14C-nitroglycerin binding by the proteins of rat blood plasma. Over the concentration range of 50-500 μg of nitroglycerin/ml of plasma, approximately 60% of the drug was bound. During the course of the binding experiments, nitroglycerin was metabolized to glyceryl dinitrates. Twice as much glyceryl-1, 3-dinitrate was formed as glyceryl-1, 2-dinitrate, indicating a strongly preferential attack upon the 2-position rather than upon the terminal positions. The metabolites were also bound by plasma proteins with glyceryl-1,2-dinitrate being held more extensively (about 60%) than glyceryl-1,3-dinitrate (35%).

Bilirubin: Chemical Properties IN 1936, on the occasion of being awarded an honorary doctorate by Harvard University, Hans Fischer was described "as the man who taught us what makes grass green and...