Nitrate sorption to biochar following chemical oxidation.

Biochar amendments can reduce nitrate (NO3) leaching in agricultural soil. It has been hypothesized that functional groups on the biochar surface from oxidation can increase NO3 sorption. This study evaluates the effect of chemical oxidation of biochar on NO3 sorption characteristics. Eight biochars, made from wood and corn cobs, underwent sodium hypochlorite (NaClO) and hydrogen peroxide (H2O2) oxidation and then assessed for NO3 sorption capacity using batch isotherm methods. The unoxidized and oxidized biochar produced at low temperatures (400 °C) had no significant NO3 sorption. Oxidized biochars produced at higher temperatures (600 °C and 700 °C) had calculated maximum NO3 sorption capacities (Smax) ranging from 0.50 to 3.97 mg NO3-N g-1. Biochar oxidations with 50 mmol NaClO g-1 (N50) in combination with an acid wash (AW) had the largest estimated sorption capacities of 3.68, 3.97, and 1.46 mg NO3-N g-1 for CTN50,AW, BW3N50,AW, and CC3N50,AW, respectively. Sorption capacity of wood-based biochars was higher than corn cob biochars due to increased oxidation as measured by total acid group content (TAGC). Wood biochar Smax values were correlated with ΔTAGC (R2 = 0.86), with a slope of 1.2 µmol NO3-N µmol TAGC-1 suggesting that cationic bridging of NO3 to oxidized sites is the primary mechanism for NO3 sorption.

Control of inflammation decreases the need for subsequent esophageal dilation in patients with eosinophilic esophagitis.

It is unknown if successful control of esophageal inflammation in eosinophilic esophagitis (EoE) decreases the need for subsequent esophageal dilation. We aimed to determine whether histologic response to topical steroid treatment decreases the likelihood and frequency of subsequent esophageal dilation. We conducted a retrospective cohort study. Patients with an incident diagnosis of EoE were included if they had an initial esophageal dilation, received topical steroids, and had a subsequent endoscopy with biopsies. The number of dilations performed in each group was determined, and histologic responders (<15 eos/hpf) were compared to nonresponders. The 55 EoE patients included (27 responders and 28 nonresponders) underwent a mean of 3.0 dilations over a median follow-up of 19 months. Responders required fewer dilations than nonresponders (1.6 vs. 4.6, P = 0.03), after adjusting for potential confounders. Despite undergoing significantly fewer dilations, responders achieved a similar increase in esophageal diameter with dilation (4.9 vs. 5.0 mm; P = 0.92). In EoE patients undergoing esophageal dilation at baseline, control of inflammation with topical steroids was associated with a 65% decrease in the number of subsequent dilations to maintain the same esophageal caliber. This suggests that inflammation control is an important goal in patients with fibrostenotic changes of EoE.

Effect of Wood Biochar in Manure-Applied Sand Columns on Leachate Quality.

Agricultural operations can pose a threat to the quality of nearby water sources particularly from nitrogen (N) and phosphorus (P) losses following land application of manure. Biochar application to soils has the potential to ameliorate degraded soils and reduce nutrient leaching to groundwater. The effects of amending sand soil columns with hybrid poplar biochar ( spp.) made by a slow-pyrolysis process at 450°C at varying rates (0, 1, 2, and 5% by weight) with repeated dairy manure applications over a 56-wk period was examined to evaluate the impact to leachate water quality. Increasing levels of biochar decreased cumulative levels of total N (TN) by 21 to 59%, nitrate (NO-N) by 17 to 46%, and ammonia (NH-N + NH-N) by 46 to 90% in leachate but increased cumulative leaching of total P (TP). Overall leachate pH was increased and peak levels of 5-d biological oxygen demand (BOD) in leachate after manure application were decreased with increasing levels of biochar amendment. The results from this study indicate that biochar amendments could be effective in reducing nitrogen leaching from soils, though further study is needed to determine practical application in a field setting.

Saxagliptin and sitagliptin in adult patients with type 2 diabetes: a systematic review and meta-analysis.

The objective of this study is to compare the efficacy and safety of sitagliptin and saxagliptin with placebo and other hypoglycaemic medications in adults with type 2 diabetes. We searched MEDLINE®, Embase, the Cochrane Library and the International Pharmaceuticals from their inception through 3 February 2011. Studies were included of adults with type 2 diabetes that were 12 weeks or more in duration. Meta-analyses were conducted when included studies were homogenous enough to justify combining their results. A total of 32 articles met inclusion criteria. Sitagliptin 100 mg monotherapy and saxagliptin 5 mg resulted in greater HbA1c reduction compared to placebo [weighted mean difference (WMD) -0.82%, 95% CI -0.95 to -0.70 and WMD -0.70, 95% CI -0.84 to -0.56, respectively]. Sitagliptin was similar to sulfonylureas for HbA1c reduction (WMD 0.08%, 95% CI 0-0.16, 3 trials) and to saxagliptin in one head-to-head trial. There was no statistically significant difference in hypoglycaemia between sitagliptin (pooled RR 1.55, 95% CI 0.55-4.36) or saxagliptin (pooled RR 1.04, 95% CI 0.28-3.81) and placebo. Sitagliptin and saxagliptin result in similar modest HbA1c reductions and do not increase the risk of hypoglycaemia unless combined with other therapies. Their role in the long-term treatment of type 2 diabetes remains unclear given the lack of long-term data on efficacy, harms and health outcomes.

Meta-analysis of the Risk of Torsades de Pointes in patients treated with intravenous racemic sotalol.

OBJECTIVE: Intravenous (IV) racemic sotalol is useful for the treatment of multiple tachydysrhythmias. The authors hypothesized that the risk of torsades de pointes (TdP) in patients treated with a single IV infusion of sotalol is lower than the 2-4% risk associated with chronic oral sotalol therapy. METHODS: A MEDLINE search under the subject heading "sotalol" was made of all publications involving humans written in English or German from 1966 to October 1, 2000. A meta-analysis of all original reports including patients who were given a single infusion of at least 1.5 mg/kg or 100 mg of IV sotalol over 30 minutes or less was performed. Potential variables predictive of TdP were assessed. The primary outcome was the observation of TdP associated with IV sotalol infusion. Secondary measurements included hypotension, bradycardia, and worsening of congestive heart failure. All excluded studies and case reports were also examined for evidence of TdP associated with IV sotalol treatment. RESULTS: The search included 1,005 publications. There were 37 reports in which 962 patients received IV sotalol and met the inclusion criteria. There was one report of self-terminating TdP lasting 10 seconds among the 962 patients included in the study. There was no report of TdP associated with only IV racemic sotalol administration in any of the excluded studies. If it is assumed that the risk of TdP is homogeneous in the population of patients treated with IV sotalol, then based on the 962 included patients, the rate of TdP is 0.1% (95% CI = 0.003% to 0.6%). CONCLUSIONS: The overall risk of TdP in patients treated with a single infusion of IV sotalol is low compared with that in patients given chronic oral sotalol therapy.

Testing neonate-infant membrane oxygenators with the University of Texas neonatal pulsatile cardiopulmonary bypass system in vitro.

Neurologic complications are already well documented after cardiopulmonary bypass (CPB) procedures in neonates and infants. Physiologic pulsatile flow CPB systems may be the alternative to the currently used steady-flow CPB circuits. In addition to the pulsatile pump, a membrane oxygenator should be chosen carefully, because only a few membrane oxygenators are suitable for physiologic pulsatile flow. We have tested four different types of neonate-infant membrane oxygenators for physiologic pulsatility with The University of Texas neonate-infant pulsatile CPB system in vitro. Evaluation criteria were based on mean ejection time, extracorporeal circuit (ECC) pressure, and upstroke of dp/dt. The results suggested that the Capiox 308 hollow-fibre membrane oxygenator produced the best physiologic pulsatile waveform according to the ejection time, ECC pressure, and the upstroke of dp/dt. The Minimax Plus and Masterflo Infant hollow-fibre membrane oxygenators also produced adequate pulsatile flow. Only the Variable Prime Cobe Membrane Lung (VPCML) Plus flat-sheet membrane oxygenator failed to reach the criteria for physiologic pulsatility. Depending on the oxygenator used, the lowest priming volume of the infant CPB circuit was 415 ml and the highest 520 ml.

The type of aortic cannula and membrane oxygenator affect the pulsatile waveform morphology produced by a neonate-infant cardiopulmonary bypass system in vivo.

Although the debate still continues over the effectiveness of pulsatile versus nonpulsatile perfusion, it has been clearly proven that there are several significant physiological benefits of pulsatile perfusion during cardiopulmonary bypass (CPB) compared to nonpulsatile perfusion. However, the components of the extracorporeal circuit have not been fully investigated regarding the quality of the pulsatility. In addition, most of these results have been gathered from adult patients, not from neonates and infants. We have designed and tested a neonate-infant pulsatile CPB system using 2 different types of 10 Fr aortic cannulas and membrane oxygenators in 3 kg piglets to evaluate the effects of these components on the pulsatile waveform produced by the system. In terms of the methods, Group 1 (Capiox 308 hollow-fiber membrane oxygenator and DLP aortic cannula with a very short 10 Fr tip [n = 2]) was subjected to a 2 h period of normothermic pulsatile CPB with a pump flow rate of 150 ml/kg/min. Data were obtained at 5, 30, 60, 90, and 120 min of CPB. In Group 2 (Capiox 308 hollow-fiber membrane oxygenator and Elecath aortic cannula with a very long 10 Fr tip [n = 7]) and Group 3 (cobe VPCML Plus flat sheet membrane oxygenator and DLP aortic cannula with a very short 10 Fr tip [n = 7]), the subjects' nasopharyngeal temperatures were reduced to 18 degrees C followed by 1 h of deep hypothermic circulatory arrest (DHCA) and then 40 min rewarming. Data were obtained during normothermic CPB in the pre- and post-DHCA periods. The criteria of pulsatility evaluations were based upon pulse pressure (between 30 and 40 mm Hg), aortic dp/dt (greater than 1000 mm Hg/s), and ejection time (less than 250 ms). The results showed that Group 1 produced flow which was significantly more pulsatile than that of the other 2 groups. Although the same oxygenator was used for Group 2, the quality of the pulsatile flow decreased when using a different aortic cannula. Group 3 did not meet any of the criteria for physiologic pulsatility. In conclusion these data suggest that in addition to a pulsatile pump, the aortic cannula and the membrane oxygenator must be chosen carefully to achieve physiologic pulsatile flow during CPB.

Error associated with the choice of an aortic cannula in measuring regional cerebral blood flow with microspheres during pulsatile CPB in a neonatal piglet model.

The effectiveness of an infant pulsatile cardiopulmonary bypass (CPB) system on maintaining regional cerebral blood flow (CBF) using two different types of aortic cannulae in 3 kg piglets has been investigated. The University of Texas Neonatal Pulsatile Pump was used with either a DLP (Group I, n = 6) or an Elecath (Group II, n = 7) 10Fr aortic cannula. In all the subjects, nasopharyngeal temperature was reduced to 18 degrees C, followed by 1 hr of deep hypothermic circulatory arrest (DHCA), then 45 min of rewarming. During cooling and rewarming, alpha-stat blood gas management was used. The radionuclide labeled microsphere technique was used to determine blood flows in the cerebellum, basal ganglia, brainstem, right and left hemispheres, as well as global CBF (ml/100 g/min). When the DLP aortic cannula was used, regional and global CBF appeared to be higher pre- and post DHCA. In both groups regional CBF was significantly decreased following DHCA. Although better pulsatile flow was attained using the DLP cannula and this may have resulted in higher regional CBF, these results must be interpreted in light of the large standard deviations noted when this cannula was chosen for the studies. These results demonstrate the importance of choosing an appropriate aortic cannula for measuring regional CBF with a pulsatile neonate-infant CPB system.

Enhancement of brain p0(2) during cardiopulmonary bypass using a hyperosmolar oxygen carrying solution.

During the past decade a new syndrome has been recognized: cerebral hypoxia secondary to cardiopulmonary bypass, resulting in impairment of cognitive memory. The incidence of the syndrome appears to be no less that 30% in patients over 65 years of age undergoing cardiac surgery. There are several factors contributing to hypoxia produced by cardiopulmonary bypass. One of these factors is crystalloid pump prime and replacement solutions devoid of (1) oxygen carrying capacity and (2) devoid of protein and its colloid osmotic pressure. This shortcoming of cardiopulmonary crystalloid solutions is partially responsible for two of the three major pathologic effects of cardiopulmonary bypass: (1) hypoxia (2) interstitial fluid accumulation (anasarca, water-logging, edema). This report describes an oxygen carrying hyperosmolar solution which enhances brain p0(2) and diminishes interstitial fluid accumulation. This blood substitute consists of perfluorcarbons and saccharides, but could consist of a hemoglobin variant plus hyperosmolar ingredients other than saccharides. The advantage of a perfluorochemical is its ability to access small channels and to be centrifuged off the patient post-operatively with a cell saver. The advantage of saccharides is that they can be metabolized by the patient for energy, and they produce a moderate diuresis coming off bypass.

Regional blood flow during pulsatile cardiopulmonary bypass and after circulatory arrest in an infant model.

BACKGROUND: Pulsatile perfusion systems have been proposed as a means of improving end-organ perfusion during and after cardiopulmonary bypass. Few attempts have been made to study this issue in an infant model. METHODS: Neonatal piglets were subjected to nonpulsatile (n = 6) or pulsatile (n = 7) cardiopulmonary bypass and 60 minutes of circulatory arrest. Cerebral, renal, and myocardial blood flow measurements were obtained at baseline, on bypass before and after circulatory arrest, and after bypass. RESULTS: Cerebral blood flow did not differ between groups at any time and was diminished equally in both groups after circulatory arrest. Renal blood flow was diminished in both groups during bypass but was significantly better in the pulsatile group than in the nonpulsatile group prior to, but not after, circulatory arrest. Myocardial blood flow was maintained at or above baseline in the pulsatile group throughout the study, but in the nonpulsatile group, it was significantly lower than baseline during CPB prior to circulatory arrest and lower compared with baseline and with the pulsatile group 60 minutes after CPB. CONCLUSIONS: Pulsatile bypass does not improve recovery of cerebral blood flow after circulatory arrest, may improve renal perfusion during bypass but does not improve its recovery after ischemia, and may have beneficial effects on myocardial blood flow during bypass and after ischemia compared with nonpulsatile bypass in this infant model.

Changes in brain pH, PO2, PCO2, cerebral blood flow, and blood gases induced by a hyperosmolar oxyreplete hemosubstitute during cardiopulmonary bypass.

Eleven goats (mean weight, 69 +/- 16 kg) underwent 5 hrs of normothermic nonpulsatile cardiopulmonary bypass (CPB) using as priming fluid either a Ringer's based crystalloid priming solution (CP, n = 5) of a hyperosmolar oxyreplete hemosubstitute (HS, n = 6). The HS contained 20% w/v perfluorocarbon (perfluorodecalin), its osmolarity was 800-900 mOsm/1, and the administered dose of perfluorocarbon was 30-50 ml/kg. Otherwise, the experimental procedure was identical for both groups. PaCO2 was maintained above 35 mmHg and blood flow rate at 65 ml/kg. Brain tissue pH, PO2, and PCO2, cerebral blood flow (CBF), arterial and venous blood gases, and other systemic variables were monitored. During CPB, PVO2 and brain tissue PO2 were increased significantly in the HS group. The CBF per kilogram of weight also was significantly higher in the HS group. Metabolic acidosis developed in both groups and, surprisingly, brain tissue pH and pHV were lower in the HS group. The mean values of PVCO2 and brain tissue PCO2 indicate that brain tissue hypercapnia also occurred in both groups. The HS provided long-term stability and compatibility with electrolytes, and did not cause major complications or allergic reactions during CPB. Perfluorocarbon based HSs improve tissue oxygenation, eliminate the risk of infection due to homologous transfusions, do not require blood type matching, have a shelf life longer than that of blood, and, therefore, they can be an important factor in diminishing the incidence of complications after CPB.

Design and performance of a physiologic pulsatile flow neonate-infant cardiopulmonary bypass system.

The authors have designed an alternative infant cardiopulmonary bypass (CPB) system using the University of Texas neonatal pulsatile pump, which produces physiologic pulsatile flow and allows a low priming volume. This system has been tested with normothermic CPB (n = 8), and deep hypothermic circulatory arrest (n = 14) in 3 kg piglets. Data obtained during these studies suggest that this system can produce flow characteristics that approximate normal physiologic values. Unlike other pulsatile pumps, this pump can produce a very small stroke volume, ranging from 0.5 to 7.1 ml with a pump rate of 120 beats/min. These stroke volumes correspond to our target value of 1 ml/kg body weight. This system is designed to cause minimal hemodilution and minimal exposure of blood to foreign surface areas. The pump does not produce negative pressure, and therefore the venous reservoir is not essential, and only a cardiotomy reservoir is required. Conclusions after in vivo testing are, first, that physiologic pulsatile flow can be achieved readily with this system using a 10 Fr aortic cannula in 3 kg piglets; and second, that a significant reduction in priming volume and hemodilution can be obtained using this system.

A single pulsatile pump for total biventricular cardiac support using patient lung ventilation.

An extracorporeal pulsatile heart pump has been modified to render biventricular cardiac support while maintaining automatic volume balance between the left and right sides. The device consists of two independent fluid circuits, externally valved and compressed by a common pusher plate configuration. Because the pusher plate compresses both circuits simultaneously, the volume-heavy side is unloaded via larger stroke volumes until the two sides achieve a balanced stroke volume. The process is automatic from beat-to-beat and is not dependent upon external pressure or flow transducers to maintain equilibrium. Two in vivo studies in pigs weighing 25 kg have demonstrated the feasibility of the concept, with physiologic aortic and pulmonary artery flow during 2 hr of ac-induced ventricular fibrillation and oscillatory ventilator support via left atrium-to-aorta and right atrium-to-pulmonary artery cannulation. Efforts to scale up to human adult size requirements have resulted in in vitro outputs of up to 7.0 L/min in each circuit.

Design of a physiologic pulsatile flow cardiopulmonary bypass system for neonates and infants.

Cardiopulmonary bypass surgical techniques that allow a surgeon to operate on the infant's heart use an extracorporeal circuit consisting of a pump, oxygenator, arterial and venous reservoirs, cannulae, an arterial filter, and tubing. The extracorporeal technique currently used in infants and neonates is sometimes associated with neurologic damage. We are developing a modified cardiopulmonary bypass system for neonates that has been tested in vitro and in one animal in vivo. Unlike other extracorporeal circuits which use steady flow, this system utilizes pulsatile flow, a low prime volume (500 ml) and a closed circuit. During in vitro experiments, the pseudo patient's mean arterial pressure was kept constant at 40 mmHg and the extracorporeal circuit pressure did not exceed a mean pressure of 200 mmHg. In our single in vivo experiment, the primary objective was to determine whether physiologic pulsatility with a 10 F (3.3 mm) aortic cannula could be achieved. The results suggest that this is possible.

Monitoring of blood gases during prolonged experimental cardiopulmonary bypass and their relationship to brain pH, PO2, and PCO2.

Eight adult goats under went 5 hr of normothermic cardiopulmonary bypass (CPB) with pulsatile (n = 3) and nonpulsatile flow (n = 5). PaCO2 was maintained at 30-40 mmHg and blood flow rate at 50 ml/min/kg. Brain tissue pH, PO2, and PCO2, arterial and venous blood gases, and other systemic variables were monitored. No significant differences in brain electrochemistry between pulsatile and nonpulsatile perfusion were observed owing to the large variability of the results and the small number of experiments. The overall data for brain tissue pH, PO2, and PCO2 were analyzed and compared to the results of arterial and venous pH, PO2, and PCO2. Brain acidosis developed at the onset of bypass, and the values for brain tissue pH dissociated from those of blood pH, suggesting that hemodilution and the initial body response to CPB are involved in its development. Brain hypercapnia also developed during CPB, the values of brain tissue PCO2 dissociated from those of blood PCO2, and brain hypercapnia appears to be secondary to brain acidosis. Brain tissue PO2 closely followed the values of PvO2, suggesting that PvO2 can be an indicator of brain tissue PO2 during normothermic CPB and must be monitored during the procedure. Brain tissue acidosis is evidently related to neurologic dysfunction after CPB, and must be addressed. Replacement of the priming solution with whole blood or artificial blood, reduction of the priming volume, and application of vigorous pulsatile flow appear feasible interventions to mitigate brain tissue acidosis during CPB.

Hemodialysis: evidence of enhanced molecular clearance and ultrafiltration volume by using pulsatile flow.

We describe several in vitro experiments showing evidence that pulsatile flow hemodialysis enhances ultrafiltration volume and molecular clearance as compared with steady flow hemodialysis. A new pulsatile pump and a conventional roller pump were compared using different hollow fiber dialyzers and a simulated blood solution containing urea, aspartame and vitamin B-12 at different flow rates and configurations. Ultrafiltration volume and concentration of urea, aspartame and B-12 were measured and molecular clearance (K) calculated. Ultrafiltration volume markedly increased with pulsatile flow. After 10 min K for urea with pulsatile flow was higher in all experiments even when ultrafiltration was prevented. Clearance of aspartame and B-12 also increased with pulsatile flow. We propose three mechanisms by which pulsatile flow is more efficient than steady flow hemodialysis: greater fluid energy, avoidance of molecular channeling and avoidance of membrane layering. We hypothesize that using pulsatile flow in hemodialysis can significantly shorten the duration of dialysis sessions for most of the patients, and consequently reduce the duration of the procedure and its cost.

Hydrogen fluoride catalyzed migration of side chain protecting groups onto Fmoc during solid phase peptide synthesis. Characterization by CF-FAB analysis of carboxypeptidase digestions and NMR spectroscopy.

The solid-phase synthesis of the N alpha-Fmoc analog of protein kinase C substrate (PKCS, Lys-Arg-Ala-Lys-Ala-Lys-Thr-Thr-Lys-Lys-Arg) was characterized by low recovery from the resin and the concomitant appearance of four impurities. FAB-MS revealed molecular weights for two of these impurities that corresponded to the desired peptide plus Tos or Bzl. The other two were justified by invoking a CO2 elimination of the Clz protecting group to yield: 1) peptide plus 2-chlorobenzyl (ClBzl) and 2) peptide plus ClBzl and Tos. A CF-FAB analysis of carboxypeptidase digestions allowed observation of peptide cleavage down to an ion corresponding to lysine, Fmoc, and the corresponding protecting group(s). These data revealed that the impurities were not the result of incomplete deprotection but the result of migration of the protecting groups to the N-terminal end of the peptide. NMR experiments were subsequently performed and revealed the exact site of substitution: the meta positions of the N-terminal Fmoc. These impurities are presumed to arise by electrophilic aromatic substitution of the fluorene group during HF treatment. The desired Fmoc analog served as a convenient, albeit low-yielding, intermediate for purification of the highly charged PKCS by preparative self-displacement HPLC.