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Background: Glucose oxidase (GOx)-based blood glucose monitors (BGMs) are influenced by the partial pressure of oxygen (Po 2 ) within the applied sample. Limited in-clinic data exists regarding the quantitative effect of Po 2 in unmanipulated capillary fingertip blood samples across physiologically representative glucose and Po 2 ranges., Method: Clinical accuracy data were collected as part of a BGM manufacturer's ongoing post-market surveillance program for a commercially available GOx-based BGM test-strip. The data set comprised 29 901 paired BGM-comparator readings and corresponding Po 2 values from 5 428 blood samples from a panel of 975 subjects., Results: A linear regression-calculated bias range of 5.22% (+0.72% [low Po 2 : 45 mm Hg] to -4.5% [high Po 2 : 105 mm Hg]); biases calculated as absolute at <100 mg/dL glucose was found. Below the nominal Po 2 of 75 mm Hg, a linear regression bias of +3.14% was calculated at low Po 2 , while negligible impact on bias (regression slope: +0.002%) was observed at higher than nominal levels (>75 mm Hg). When evaluating BGM performance under corner conditions of low (<70 mg/dL) and high (>180 mg/dL) glucose, combined with low and high Po 2 , linear regression biases ranged from +1.52% to -5.32% within this small group of subjects and with no readings recorded at <70 mg/dL glucose at low and high Po 2 ., Conclusions: Data from this large-scale clinical study, performed on unmanipulated fingertip capillary bloods from a diverse diabetes population, indicate Po 2 sensitivity of the BGM to be markedly lower than published studies, which are mainly laboratory-based, requiring artificial manipulation of oxygen levels in aliquots of venous blood., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SS, SP, HC, and MG are employees of LifeScan Scotland, Ltd.

The enzymatic biofuel cell (EBFC) has been considered as a promising implantable energy generator because it can extract energy from a living body without any harm to the host. However, an unprotected enzyme will be destabilized and even eventually be deactivated in human blood. Thus, the performance of implantable EBFC has received barely any improvement. It is therefore a breakthrough in realizing a superior efficient EBFC that can work stably in human blood which relies in protecting the enzyme to defend it from the attack of biological molecules in human blood. Herein, we innovatively created a single-walled carbon nanotube (SWCNT) and cascaded enzyme-glucose oxidase (GOx)/horseradish peroxidase (HRP) coembedded hydrophilic MAF-7 biocatalyst (SWCNT-MAF-7-GOx/HRP). The SWCNT-MAF-7-GOx/HRP is highly stable in electrocatalytic activity even when it is exposed to high temperature and some molecular inhibitors. In addition, we were pleasantly surprised to find that the electrocatalytic activity of GOx/HRP in hydrophilic SWCNT-MAF-7 far surpasses that of the GOx/HRP in hydrophobic SWCNT-ZIF-8. In human whole blood, the SWCNT-MAF-7-GOx/HRP catalytic EBFC exhibits an eightfold increase in power density (119 μW cm -2 vs 14 μW cm -2 ) and 13-fold increase in stability in comparison with the EBFC based on an unprotected enzyme. In this study, the application of metal-organic framework-based encapsulation techniques in the field of biofuel cells is successfully realized, breaking a new path for creating implantable bioelectrical-generating devices.

Background and aim This study was conducted to investigate the association between serum nitric oxide metabolites (NOx) and the risk of chronic kidney disease (CKD). Methods We recruited 3462 and 2504 participants of the Tehran Lipid and Glucose Study (TLGS), for a cross-sectional and prospective analysis, respectively. Serum NOx concentrations were measured at baseline (2006-2008), and demographics, anthropometrics and biochemical variables were evaluated at baseline and again after 3 years (2009-2011). Estimated glomerular filtration rate (eGFR) and CKD were defined. Association between serum NOx and CKD in the cross-sectional phase and the predictability of NOx in CKD occurrence were assessed using multivariable logistic regression models with adjustment for confounders. Results Mean age of participants was 45.0 ± 15.9 years at baseline and 40.5% were male. The prevalence of CKD was 17.9% (13.4% in men, 21.0% in women) at baseline, at which point, marginally significant odds of CKD in the highest tertile of serum NOx in men (OR = 1.53, 95% CI = 0.96-2.45, p for trend = 0.047) and a significant odds of CKD in women (OR = 2.48, 95% CI = 1.76-3.49, p for trend = 0.001) were observed. After a 3-year follow-up, in women, risk of CKD was higher in the highest compared to the lowest NOx tertiles (OR = 1.86, 95% CI = 1.10-3.14, p for trend = 0.032) but no significant association was observed in men. Conclusion Serum NOx level was found to be an independent predictor of CKD in women; it could be a valuable surrogate for prediction of renal dysfunction in women and help to identify high-risk subjects.

Background: The partial pressure of oxygen (pO2) in blood samples can affect glucose measurements with oxygen-sensitive systems. In this study, we assessed the influence of different pO2 levels on blood glucose (BG) measurements with five glucose oxidase (GOD) systems and one glucose dehydrogenase (GDH) system. All selected GOD systems were indicated by the manufacturers to be sensitive to increased oxygen content of the blood sample., Materials and Methods: Venous blood samples of 16 subjects (eight women, eight men; mean age, 52 years; three with type 1 diabetes, four with type 2 diabetes, and nine without diabetes) were collected. Aliquots of each sample were adjusted to the following pO2 values: ≤45 mm Hg, approximately 70 mm Hg, and ≥150 mm Hg. For each system, five consecutive measurements on each sample were performed using the same test strip lot. Relative differences between the mean BG value at a pO2 level of approximately 70 mm Hg, which was considered to be similar to pO2 values in capillary blood samples, and the mean BG value at pO2 levels ≤45 mm Hg and ≥150 mm Hg were calculated., Results: The GOD systems showed mean relative differences between 11.8% and 44.5% at pO2 values ≤45 mm Hg and between -14.6% and -21.2% at pO2 values ≥150 mm Hg. For the GDH system, the mean relative differences were -0.3% and -0.2% at pO2 values ≤45 mm Hg and ≥150 mm Hg, respectively., Conclusions: The magnitude of the pO2 impact on BG measurements seems to vary among the tested oxygen-sensitive GOD systems. The pO2 range in which oxygen-sensitive systems operate well should be provided in the product information.

Background: Partial pressure of oxygen (pO2) in blood samples can affect blood glucose (BG) measurements, particularly in systems that employ the glucose oxidase (GOx) enzyme reaction on test strips. In this study, we assessed the impact of different pO2 values on the performance of five GOx systems and one glucose dehydrogenase (GDH) system. Two of the GOx systems are labeled by the manufacturers to be sensitive to increased blood oxygen content, while the other three GOx systems are not., Methods: Aliquots of 20 venous samples were adjusted to the following pO2 values: <45, ~70, and ≥150 mmHg. For each system, five consecutive measurements on each sample aliquot were performed using the same test strip lot. Relative differences between the mean BG results at pO2 ~70 mmHg, which is considered to be similar to pO2 in capillary blood samples, and the mean BG result at pO2 <45 and ≥150 mmHg were calculated., Results: For all tested GOx systems, mean relative differences in the BG measurement results were between 6.1% and 22.6% at pO2 <45 mmHg and between -7.9% and -14.9% at pO2 ≥150 mmHg. For both pO2 levels, relative differences of all tested GOx systems were significant (p < .0001). The GDH system showed mean relative differences of -1.0% and -0.4% at pO2 values <45 and ≥150 mmHg, respectively, which were not significant., Conclusions: These data suggest that capillary blood pO2 variations lead to clinically relevant BG measurement deviations in GOx systems, even in GOx systems that are not labeled as being oxygen sensitive., (© 2013 Diabetes Technology Society.)

Objective: The purpose of this study was to evaluate the accuracy of a novel commercial glucose-oxidase (GO)-based glucometer in measuring glucose concentrations in arterial blood samples collected from premature infants., Patients and Methods: A commercial glucometer, which is a plasma separation GO-based glucometer, was employed to compare the accuracy of the commercial blood glucometer with that of a standard glucose analyser for monitoring blood glucose levels in premature infants. Arterial blood samples were collected and analysed, including samples adjusted for specific glucose (3.6 mmol/L, 8.3 mmol/L and 16.7 mmol/L) and PaO2 levels (range, 40-400 mm Hg)., Results: In total, 159 samples were collected. Bland-Altman analysis showed good correlation between the commercial glucometer and standard glucose analyser. Error-grid analysis revealed that all of the results were within zone A (ie, the clinically accurate estimate zone). The biases between the two systems were low at different PaO2 levels and haematocrits. Finally, the influence of different PaO2 levels was within acceptable ranges., Conclusions: The GO-based glucometer evaluated in this study provides accurate results even when measured at high PaO2 and different haematocrits and is suitable for measuring arterial glucose levels in premature infants.

In this study, we design a homogeneous system consisting of Ag nanoprisms and glucose oxidase (GOx) for simple, sensitive, and low-cost colorimetric sensing of glucose in serum. The unmodified Ag nanoprisms and GOx are first mixed with each other. Glucose is then added in the homogeneous mixture. Finally, the nanoplates are etched from triangle to round by H2O2 produced by the enzymatic oxidation, which leads to a more than 120 nm blue shift of the surface plasmon resonance (SPR) absorption band of the Ag nanoplates. This large wavelength shift can be used not only for visual detection (from blue to mauve) of glucose by naked eyes but for reliable and convenient glucose quantification in the range from 2.0 × 10(-7) to 1.0 × 10(-4) M. The detection limit is as low as 2.0 × 10(-7) M, because the used Ag nanoprisms possess (1) highly reactive edges/tips and (2) strongly tip sharpness and aspect ratio dependent SPR absorption. Owing to ultrahigh sensitivity, only 10-20 μL of serum is enough for a one-time determination. The proposed glucose sensor has great potential in the applications of point-of-care diagnostics, especially for third-world countries where high-tech diagnostics aids are inaccessible to the bulk of the population.

Study Objectives: Obesity is a common feature of narcolepsy. In addition, an increased occurrence of non-insulin dependent diabetes has been reported. So far, it is not known whether glucose metabolism in narcolepsy is disturbed due to, or independently of obesity., Design: Case-control study., Setting: Sleep medicine clinic at a research institute., Patients: We studied 17 patients with narcolepsy/cataplexy compared to 17 healthy controls matched for age, sex, and body mass index (BMI)., Interventions: A 75-g oral glucose tolerance test was performed., Measurements: Glucose tolerance was determined by computing plasma glucose curve following oral glucose challenge for 240 minutes; insulin sensitivity and insulin secretion by homeostasis model assessment and minimal model analysis., Results: Standard outcome measures and indices of the oral glucose tolerance test did not differ between the patient group and the group of control subjects., Conclusions: In this study, no clinically relevant pathologic findings in the glucose metabolism of narcoleptic patients compared to weight matched controls were found. Thus, narcolepsy is unlikely to be a risk factor per se for impaired glucose tolerance or diabetes.

Objectives: To determine whether there is a relationship between electroencephalography patterns and hypoglycemia, by using simultaneous cot-side amplitude integrated electroencephalography (aEEG) and continuous interstitial glucose monitoring, and whether non-glucose cerebral fuels modified these patterns., Study Design: Eligible babies were ≥ 32 weeks gestation, at risk for hypoglycemia, and admitted to the neonatal intensive care unit. Electrodes were placed in C3-P3, C4-P4 O1-O2 montages. A continuous interstitial glucose sensor was placed subcutaneously, and blood glucose was measured by using the glucose oxidase method. Non-glucose cerebral fuels were measured at study entry, exit, and during recognized hypoglycemia., Results: A total of 101 babies were enrolled, with a median weight of 2179 g and gestation of 35 weeks. Twenty-four of the babies had aEEG recordings, and glucose concentrations were low (< 2.6 mM). There were 103 episodes of low glucose concentrations lasting 5 to 475 minutes, but no observable changes in aEEG variables. Plasma concentrations of lactate, beta-hydroxybutyrate, and glycerol were low and did not alter during hypoglycemia., Conclusions: Cot-side aEEG was not useful for the detection of neurological changes during mild hypoglycemia. Plasma concentrations of non-glucose cerebral fuels were low and unlikely to provide substantial neuroprotection., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Gastrointestinal symptoms are fairly common in diabetes mellitus. Glimepride, is a latest second generation sulfonylurea used for the treatment of type II diabetes mellitus, is a insulin secrectagogue; indirectly, it also increases insulin secretion and its specific effect on pancreatic ATP-dependent K(+) channel inhibition. Esomeprazole, the (S)-isomer of omeprazole, is the first proton pump inhibitors developed as a single isomer for the treatment of acid-peptic diseases by specific inhibition of H(+)/K(+)-ATPase in gastric parietal cell. Since there is possibility for drug interaction leading to decreased activity of glimepride, the present study was conducted to evaluate the effect of the combination. Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 135 μg/kg bd.wt. of glimepride, 3.6 mg/kg bd.wt. of esomeprazole, and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with doses 70 μg/1.5 kg bd. wt. of glimepride, 1.8 mg/1.5 kg bd. wt. of esomeprazole, and their combination given orally. The blood samples were collected at 0, 1, 2, 4, 8, 12, 18, 24 h and analyzed for glucose levels by GOD/POD method and insulin in diabetic rats by radioimmunoassay methods. Glimepride produced hypoglycaemic/antidiabetic activity in normal and diabetic rats activity with peak activity maximum at 4 h and hypoglycemic activity in normal rabbits maximum at 4 h and esomeprazole increases the insulin levels in diabetic rats. The study also suggests the necessity to readjust the dose of glimepride, when used concomitantly with esomeprazole.

Background: The PalmLab glucometer is a newly designed plasma separation glucose oxidase (GO)-based glucometer. Past studies have shown that the accuracy of GO-based glucometers is compromised when measurements are taken in patients with high PO(2) levels. We performed a two-arm study comparing the fitness of the PalmLab blood glucometer with that of a standard glucose analyzer in monitoring blood glucose levels in pediatric patients, especially when arterial partial pressure of oxygen (PO(2)) was high., Methods: In the first arm of the study, arterial blood samples from pediatric patients were measured by the PalmLab blood glucometer and the YSI 2302 Plus Glucose/Lactate analyzer. In the second arm of the study, venous blood samples from adult volunteers were spiked with glucose water to prepare three different levels of glucose (65, 150, and 300mg/dL) and then oxygenated to six levels of PO(2) (range, 40-400mmHg). The biases of the PalmLab glucometer were calculated., Results: A total of 162 samples were collected in the first arm of the study. Results of linear regression showed that the coefficient of determination (R(2)) between PalmLab glucometer and standard glucose analyzer was 0.9864. Error grid analysis revealed that all the results were within Zone A (clinically accurate estimate zone). The biases between the two systems were low at different PO(2) levels. In the second arm of the study, the results were also unaffected by changes in PO(2)., Conclusion: The PalmLab glucometer provides accurate results in samples with high PO(2) and is suitable for measuring arterial glucose levels in pediatric patients., (Copyright © 2011. Published by Elsevier B.V.)

Background: Due to increasing numbers of people with diabetes taking part in extreme sports (e.g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior studies reported bias in blood glucose measurements using different BGMs at high altitude. We hypothesized that glucose-oxidase based BGMs are more influenced by the lower atmospheric oxygen pressure at altitude than glucose dehydrogenase based BGMs., Methodology/principal Findings: Glucose measurements at simulated altitude of nine BGMs (six glucose dehydrogenase and three glucose oxidase BGMs) were compared to glucose measurement on a similar BGM at sea level and to a laboratory glucose reference method. Venous blood samples of four different glucose levels were used. Moreover, two glucose oxidase and two glucose dehydrogenase based BGMs were evaluated at different altitudes on Mount Kilimanjaro. Accuracy criteria were set at a bias <15% from reference glucose (when >6.5 mmol/L) and <1 mmol/L from reference glucose (when <6.5 mmol/L). No significant difference was observed between measurements at simulated altitude and sea level for either glucose oxidase based BGMs or glucose dehydrogenase based BGMs as a group phenomenon. Two GDH based BGMs did not meet set performance criteria. Most BGMs are generally overestimating true glucose concentration at high altitude., Conclusion: At simulated high altitude all tested BGMs, including glucose oxidase based BGMs, did not show influence of low atmospheric oxygen pressure. All BGMs, except for two GDH based BGMs, performed within predefined criteria. At true high altitude one GDH based BGM had best precision and accuracy.

Objective: Implementation of strict glucose control in most intensive care units has resulted in increased use of point-of-care glucose devices in the intensive care unit. The aim of this study was to determine the reliability of point-of-care testing glucose meters among critically ill patients under intensive insulin treatment., Design: Prospective observational study., Patients: Intensive care unit and non-intensive care unit patients in a tertiary care teaching hospital., Measurements: A glucose oxidase method was used to validate the point-of-care testing devices. Three different point-of-care testing devices, Accu-Chek Sensor (Roche Diagnostics), Precision (Abbott Diagnostics), and HemoCue were tested. Glucose measurements were performed in duplicate by an experienced technician under standardized conditions in the hospital's laboratory, using arterial (intensive care unit patients) and arterial or venous (non-intensive care unit patients) heparinized whole blood samples., Main Results: A strong correlation was found between the glucose oxidase method and the Accu-Chek device (r = .9596, p < 0.001). Mean absolute difference between the glucose oxidase and Accu-Chek was -0.32 mmol/L (95% confidence interval -0.84 to 1.48 mmol/L). Using the International Organization for Standardization (ISO) criteria, 27 of 197 samples (13.7%) were inaccurate. In all samples that failed to meet the ISO criteria, glucose values measured by the Accu-Chek device were higher compared with the glucose oxidase method. In another set of experiments among intensive care unit patients, strong positive correlations were also found between the other point-of-care testing devices and the glucose oxidase method. However, paired samples from Accu-Chek, HemoCue, and Precision failed the ISO criteria in 9 of 82 (11.0%), 4 of 82 (4.9%), and 11 of 82 (13.4%) of cases, respectively. In non-intensive care unit patients paired samples from Accu-Chek, HemoCue, and Precision failed the ISO criteria in 3 of 120 (2.5%), 11 of 120 (9.2%), and 16 of 120 (13.3%) cases, respectively., Conclusions: Under standardized conditions, glucose results from three point-of-care testing devices were inaccurate in both intensive care unit and non-intensive care unit patients. Among intensive care unit patients, inaccurate glucose readings were most frequently falsely elevated, resulting in misinterpretation of high glucose values with subsequent inappropriate insulin administration or masking of true hypoglycemia.

Background: In recent years a number of point of care testing (POCT) glucometers were introduced on the market. We investigated the analytical variability (lot-to-lot variation, calibration error, inter-instrument and inter-operator variability) of glucose POCT systems in a university hospital environment and compared these results with the analytical needs required for tight glucose monitoring., Methods: The reference hexokinase method was compared to different POCT systems based on glucose oxidase (blood gas instruments) or glucose dehydrogenase (handheld glucometers). Based upon daily internal quality control data, total errors were calculated for the various glucose methods and the analytical variability of the glucometers was estimated., Results: The total error of the glucometers exceeded by far the desirable analytical specifications (based on a biological variability model). Lot-to-lot variation, inter-instrument variation and inter-operator variability contributed approximately equally to total variance. As in a hospital environment, distribution of hematocrit values is broad, converting blood glucose into plasma values using a fixed factor further increases variance. The percentage of outliers exceeded the ISO 15197 criteria in a broad glucose concentration range., Conclusions: Total analytical variation of handheld glucometers is larger than expected. Clinicians should be aware that the variability of glucose measurements obtained by blood gas instruments is lower than results obtained with handheld glucometers on capillary blood.

Aim: Based on the previously established method, we developed a better and stable animal model of type 2 diabetes mellitus by high-fat diet combined with multiple low-dose STZ injections. Meanwhile, this new model was used to evaluate the antidiabetic effect of berberine., Method: Wistar male rats fed with regular chow for 4 weeks received vehicle (control groups), rats fed with high-fat diet for 4 weeks received different amounts of STZ once or twice by intraperitoneal injection (diabetic model groups), and diabetic rats were treated with berberine (100 mg/kg, berberine treatment group). Intraperitoneal glucose tolerance test and insulin tolerance test were carried out. Moreover, fasting blood glucose, fasting insulin, total cholesterol, and triglyceride were measured to evaluate the dynamic blood sugar and lipid metabolism., Result: The highest successful rate (100%) was observed in rats treated with a single injection of 45 mg/kg STZ, but the plasma insulin level of this particular group was significantly decreased, and ISI has no difference compared to control group. The successful rate of 30 mg/kg STZ twice injection group was significantly high (85%) and the rats in this group presented a typical characteristic of T2DM as insulin resistance, hyperglycemia, and blood lipid disorder. All these symptoms observed in the 30 mg/kg STZ twice injection group were recovered by the treatment of berberine., Conclusion: Together, these results indicated that high-fat diet combined with multiple low doses of STZ (30 mg/kg at weekly intervals for 2 weeks) proved to be a better way for developing a stable animal model of type 2 diabetes, and this new model may be suitable for pharmaceutical screening.

[diagram: see text] Using a boronic acid receptor that was previously found to have high affinity for gluconic acid, we created a colorimetric indicator displacement assay (IDA) that can report the concentration of the product of glucose oxidase (GOx) catalyzed glucose oxidation. The color change obtained directly reflects the concentration of glucose. Our sensing ensemble was then successfully applied to determine the glucose concentration in human serum, which offers a facile, colorimetric, sensitive, and accurate glucose test.

A large proportion of violent offences in Western countries are attributable to antisocial personality disorder (APD). Several studies have shown abnormal lipid, carbohydrate and low cerebrospinal fluid (CSF) monoamine metabolite levels in habitually violent alcoholic offenders with APD, but it is not clear how these biochemical abnormalities are related to each other in this disorder. We aimed to study energy substrate metabolism among habitually violent offenders with APD. Insulin sensitivity (euglycemic insulin clamp), basal energy expenditure (indirect calorimetry), and CSF 5-hydroxyindoleacetic acid (5-HIAA) measurements were performed on 96 habitually violent antisocial male alcoholic offenders and on 40 normal male controls. Habitually violent, incarcerated offenders with APD had significantly lower non-oxidative glucose metabolism, basal glucagon, and free fatty acids when compared with normal controls, but glucose oxidation and CSF 5-HIAA did not differ markedly between these groups. The effect sizes for lower non-oxidative glucose metabolism among incarcerated and non-incarcerated APD subjects were 0.73 and 0.51, respectively, when compared with controls, indicating that this finding was not explained by incarceration. Habitually violent offenders with APD have markedly lower glucagon and non-oxidative glucose metabolism when compared with healthy controls, and these findings were more strongly associated with habitual violent offending than low CSF 5-HIAA levels, a well-established marker for impulsive violent behavior. Follow-up studies are needed to confirm if abnormal glucose and lipid metabolism can be used to predict violent offending over the course of the APD offender's life span.

Unlabelled: Epidemiological studies have documented that postprandial hyperglycemia is the main risk factor for cardiovascular diseases. It has been established that glycated hemoglobin (HbA1C) provides an integrated measure of plasma glucose (PG) of the last 2-3 months. However, the relative contribution of fasting PG (FPG) and postprandial PG (PPG) to the HbA1C value is controversial., Objective: To evaluate FPG and PPG contributions to the HbA1C value in patients with type 2 diabetes mellitus (DM2)., Methods: 53 subjects with stable DM2 were studied. They were treated with oral anti-diabetic agents (n = 27) and/or insulin (n = 26). Each subject went to 3 visits at 2-month-intervals. On each visit, FPG, PPG (2 h after breakfast and lunch), and HbA1C were measured and we provided breakfast and lunch according to their meal habits. PG was measured by glucose-oxidase and HbA1C by ion-exchange chromatography. Statistical analysis was performed by correlation coefficients at a < 0.05 P value., Results: Correlations were stronger between HbA1C and post-breakfast PG (r: 0.66-0.48), mean FPG (r: 0.64-0.41), glucose area under the curve (r: 0.64-0.46), and mean PPG (r: 0.59-0.41)., Conclusions: Measurement of post-breakfast PG showed to be another valuable tool for type 2 diabetic glucose control monitoring.

Most methods used to measure glucose concentrations in biotechnological settings are labour-intensive and/or expensive. With this in mind we have investigated the possibility of employing blood glucose meters, the use of which has the benefit of being fast, convenient and inexpensive, for this purpose. Accu-Chek Advantage (Roche Diagnostics, Indianapolis, IN, U.S.A.) and Precision QID (Medisense, Abbott Laboratories, Indianapolis, IN, U.S.A.) meters were tested using glucose samples of known concentration, at pH 7.5 and 4.8. The Accu-Chek Advantage meter uses strips containing the enzyme glucose dehydrogenase. This meter showed a linear response for glucose concentrations between 0.50 and 6.0 g/litre, and the effect of pH was small. The Precision QID meter uses strips containing the enzyme glucose oxidase and is more sensitive to pH. The displayed glucose concentrations at low pH values were consistently lower than at higher pH values. At both pH values the response curve reached a plateau, which limited the effective range of this meter to a range of 0.30-2.5 g/litre. Unlike the Precision QID meter, the Accu-Chek Advantage meter also responded to xylose and arabinose. A synergistic effect of combining sugars was observed when a mixture of sugars consisting of glucose and arabinose, or glucose and xylose, was applied: the displayed concentrations were consistently higher than was expected on the basis of the individual calibration curves. The use of glucose meters is a fast and convenient alternative to existing methods and may be of particular use for screening purposes where a high degree of accuracy is not crucial. The choice of meter should depend on the application, and in this respect the pH, expected concentration range and the presence of other sugars are among the factors that should be considered.

The objective of this investigation was to evaluate the influence of polymorphonuclear granulocytes on the performance of uncoated and cellulose acetate/Nafion coated amperometric glucose sensors in vitro. The response of these sensors was also investigated in serum. Uncoated and coated sensors showed lower sensitivities to glucose, with a significant drift in sensor output upon exposure to serum or leukocytes. Although the use of a coating resulted in higher sensitivity, the progressive loss of output was not completely prevented. Stimulated granulocytes were shown to excrete components, probably catalase and myeloperoxidase, which consumed the hydrogen peroxide formed by the oxidation of glucose. In addition, adsorbed serum proteins formed a diffusional barrier for glucose. Furthermore, serum was found to contain low-molecular weight components that alone inhibited glucose oxidase activity. Based on preliminary electrochemical results, we postulate that rabbit serum contains oxidizing substrates that compete with molecular oxygen for the acceptance of electrons from the oxidized enzyme. Consequently, future efforts should be aimed at elucidating the mechanisms involved in the interference of unknown serum components with electron transfer. In addition, further investigations have to be performed to develop an outer membrane that minimizes protein adsorption as well as the actions of inflammatory cells., (Copyright 2000 John Wiley & Sons, Inc.)

In the present study, we showed that 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a nitric oxide (NO)-independent activator of soluble guanylate cyclase, could potentiate H2O2-induced inhibition of platelet aggregation and increase of platelet cGMP levels. The synergistic effect of YC-1 and H2O2 on platelet aggregation and increases of cGMP were almost completely prevented by catalase and a selective soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or partially attenuated by the hydroxyl radical scavenger mannitol. In contrast, superoxide dismutase failed to influence H2O2/YC-1-induced inhibition of aggregation. Furthermore, YC-1 could enhance the activation of soluble guanylate cyclase caused by FeSO4/H2O2 and, this effect was prevented markedly by mannitol. These results suggest that YC-1 may enhance the antiaggregatory effect of H2O2 via the sensitization of platelet soluble guanylate cyclase. In addition, this phenomenon is, at least in part, dependent on H2O2-derived hydroxyl radical.

The preterm infant frequently requires glucose level monitorization. This paper compared determinations of blood glucose by two methods: glucose strip test and biochemistry. There was determined 464 pairs of glucose levels by both methods in 40 preterm infants receiving glucose infusion. The hypoglycemia interval showed that the precision of strips was lower than the biochemical method. The same was found in hyperglycemia interval, but the result was a few better. Concluding, the authors emphasize the use of glucose strip test only for screening and the biochemical test for treatment.

To determine if bypassing both intestinal absorption and hepatic glucose uptake by intravenous glucose infusion might increase the rate of muscle glucose oxidation above 1 g.min-1, ten endurance-trained subjects were studied during 125 min of cycling at 70% of peak oxygen uptake (VO2peak). During exercise the subjects ingested either a 15 g.100 ml-1 U-14C labelled glucose solution or H2O labelled with a U-14C glucose tracer for the determination of the rates of plasma glucose oxidation (Rox) and exogenous carbohydrate (CHO) oxidation from plasma 14C glucose and 14CO2 specific activities, and respiratory gas exchange. Simultaneously, 2-3H glucose was infused at a constant rate to measure glucose turnover, while unlabelled glucose (25% dextrose) was infused into those subjects not ingesting glucose to maintain plasma glucose concentration at 5 mmol.l-1. Despite similar plasma glucose concentrations [ingestion 5.3 (SEM 0.13) mmol.l-1; infusion 5.0 (0.09) mmol.l-1], compared to glucose infusion, CHO ingestion significantly increased plasma insulin concentrations [12.9 (1.0) vs 4.8 (0.5) mU.l-1; P < 0.05], raised total Rox values [9.5 (1.2) vs 6.2 (0.7) mmol.125 min-1 kg fat free mass-1 (FFM); P < 0.05] and rates of CHO oxidation [37.2 (2.8) vs 24.1 (3.9) mmol.125 min-1 kg FFM-1; P < 0.05]. An increased reliance on CHO metabolism with CHO ingestion was associated with a decrease in fat oxidation. Whereas the contribution from fat oxidation to energy production increased to 51 (10)% with glucose infusion, it only reached 18 (4)% with glucose ingestion (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The study included 249 patients two days before cardiovascular surgery and 73,915 control subjects. Results obtained were analyzed by grouping the individuals according to sex and age. In coronary heart disease (CHD) in males, total cholesterol was found higher than in controls (mean +/- D.S.: 241.9 +/- 44.7 vs 223.6 +/- 43.0 mg/dl, p < 0.01) between 25 and 49 years of age, this significance being lost with age. Triglycerides were also higher (197 +/- 107.3 vs 161.6 +/- 97.7 mg/dl, p < 0.01) in the CHD male population between ages 25 and 69. In CHD females, triglycerides were higher (116.9 +/- 56.2 vs 91.5 +/- 43.3 mg/dl, p < 0.05) between ages 25 and 49; cholesterol showed no difference at any of the ages studied. HDL-C was much lower in both sexes of CHD patients at all ages studied (p < 0.001). Uric acid was higher in CHD males between ages 25 and 49 (p < 0.05), this significance being lost in the older age CHD group. Other components such as glycated hemoglobin, glucose and ionized calcium, were not different from those of the control group.

The main metabolic properties of human red blood cells (RBC) overloaded with glucose catabolizing enzymes such as hexokinase and glucose oxidase were evaluated. Human erythrocytes loaded with human hexokinase metabolized 3.1 +/- 0.2 mumol/h/ml RBC of glucose, an amount double that consumed by normal and unloaded cells (1.46 +/- 0.16 mumol/h/ml RBC), while glucose oxidase-loaded erythrocytes consumed up to 5.5 +/- 0.5 mumol/h/ml RBC of glucose but with a time-dependent increase in methemoglobin formation due to the H2O2 produced in the glucose oxidase reaction. This methemoglobin production was greatly reduced while glucose consumption was increased (8.1 +/- 0.4 mumol/h/ml RBC) by coentrapment of hexokinase and glucose oxidase. Similar results were obtained in mouse red blood cells, although the role of hexokinase was less pronounced due to a higher basal level of this enzyme. When administered to diabetic mice the hexokinase/glucose oxidase-overloaded erythrocytes had a circulating half-life of 5 days and were able to regulate blood glucose at near physiological levels. A single intraperitoneal administration of 500 microliters of enzyme-loaded cells maintained a near-normal blood glucose concentration for 7 +/- 1 days, while repeated administrations at 10-day intervals were effective in the regulation of blood glucose levels for several weeks. These results suggest that enzyme-loaded erythrocytes can behave as circulating bioreactors and can provide a new way to reduce abnormally elevated blood glucose.

Human leukocytes stimulated by opsonized zymosan increase their NADPH oxidase-catalysed reduction of molecular oxygen. This leads to enhanced formation of superoxyl radicals and subsequently hydrogen peroxide. The leukocyte enzyme myeloperoxidase generates the strong microbicidal oxidant hypochlorite from hydrogen peroxide and chloride anions. Hypochlorite inactivates serum alpha 1-proteinase inhibitor, a protein which protects host tissue from digestion by proteinases, that are also secreted by stimulated leukocytes. Micromolar concentrations of a water-soluble, quaternary ammonium analogue of alpha-tocopherol (vitamin E) (3,4-dihydro-6-hydroxy-N,N,N-2,5,7,8-heptamethyl-2H-1-benzopyran-2 -ethanaminium 4-methylbenzenesulfonate) and its tertiary amine derivative (3,4-dihydro-2- (2-dimethylaminoethyl)-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol hydrochloride) were able to protect alpha 1-proteinase inhibitor from inactivation by stimulated human leukocytes. The mechanism of action of the quaternary ammonium analogue was further investigated. Selective inhibition of hydrogen peroxide formation is assumed to be the reason for its protective effect. This compound rapidly reacts with superoxyl radicals, but not with hydrogen peroxide, and is only a weak hypochlorite scavenger. It neither impedes exocytosis of elastase, nor effectively inhibits NADPH oxidase or myeloperoxidase. In contrast, superoxide dismutase, which enhances hydrogen peroxide formation, cannot protect alpha 1-proteinase inhibitor from inactivation.

The development of membranes that swell in response to glucose is reported. The membranes may prove to be useful in glucose monitoring or glucose-dependent insulin delivery. The polymers were synthesized by the radiation-induced polymerization of frozen solutions containing hydroxyethylmethacrylate, N,N-dimethylaminoethyl methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol, water, and glucose oxidase. The polymers were hydrogels, with water contents in the range of 60-90%, depending on the pH or glucose concentration. Changes in swelling and permeability of the hydrogel were caused by exposure to glucose solutions. The gluconic acid formed by the glucose oxidase catalyzed oxidation of glucose in the membrane lowered the pH of the system and thus caused the changes in the membrane. The retention of enzyme activity by the membranes in vitro and in vivo is also reported. The large differences in properties among membranes made with different chemical formulations suggest that glucose-sensitive membranes with performance characteristics needed for an artificial pancreas may be an achievable goal.

Two automated glucose oxidase methods have been evaluated with respect to accuracy, precision, recovery, linearity and various potential interferences. Trinder's method on an AutoAnalyzer II had a between-day coefficient of variation (C.V.) of 2.6% (mean 228 mg/dl), was linear to 500 mg/dl, and produced a mean recovery of 99.7%. Comparison of Trinder's method with a manual, blanked hexokinase method yielded the regression equation: TR=--1.95 + HEX (1.04); Spearman's rho correlation coefficient was: 0.974. The Beckman System I glucose method had a between-day C.V. of 1.6% (mean 198 mg/dl), was linear to 500 mg/dl, and recovered an average of 98.0% of added glucose. Comparison with the same hexokinase method yielded: SYI = 1.27 + HEX (1.02: Spearman's rho = 0.991. None of the possible interfering compounds tested caused significant deviation of results by either method within the range of concentrations encountered physiologically. Trinder's method on the AutoAnalyzer II and the System I method are accurate, precise methods and are highly recommended for routine use in the clinical laboratory.

Eosinophil and/or neutrophil leukocytes appear to have important roles in host defense against invasive, migratory helminth infestations, but the mechanisms of larval killing by leukocytes are uncertain. This study examines killing of newborn (migratory phase) larvae of Trichinella spiralis during incubation with granule preparations of human eosinophils or neutrophils and generators of hydrogen peroxide (glucose-glucose oxidase) (G-GO) or superoxide and hydrogen peroxide (xanthine-xanthine oxidase). Larvae were killed by either hydrogen peroxide-generating system in a concentration-dependent manner. Direct enumeration of surviving larvae after incubation in microtiter wells containing the appropriate reagents was used in assess larval killing. Verification of the microplate assay was demonstrated by complete loss of larval ability to incorporate [(3)H]deoxyglucose and loss of infectivity after incubation in comparable concentrations of G-GO. Larvae were highly sensitive to oxidative products; significant killing occurred after incubation with 0.12 mU glucose oxidase and complete killing occurred with 0.5 mU. Comparable killing of bacteria required over 60 mU glucose oxidase. At 5 mU glucose oxidase, killing was complete after 6 h of incubation. Killing by G-GO was inhibited by catalase but not by boiled catalase or superoxide dismutase and was enhanced by azide. Addition of peroxidase in granule pellet preparations of eosinophils or neutrophils did not enhance killing by G-GO. These data indicate a remarkable susceptibility of newborn larvae of T. spiralis to the hydrogen peroxide generated by neutrophil and eosinophil leukocytes.

A competitive enzyme immunoassay for the measurement of human plasma fibronectin (PFN) was developed, using polystyrene beads as a solid phase and glucose oxidase as a marker enzyme. This method gave a reproducible standard curve in the range of 0.5-50 micrograms/ml. The mean PFN level in normal persons was 345 micrograms/ml (standard deviation 68.4 micrograms/ml, n = 30). The PFN levels in patients with malignant, collagen and liver diseases were also measured. The mean PFN level in patients with collagen disease was significantly higher than that in normal persons, whereas the mean PFN levels in patients with malignant and liver diseases were not significantly different.

A significant difference in the amount of exhaled mercury per hour between normal and acatalasemic mice was observed in 7 of 11 experiments for different periods of time. The total amount of mercury exhaled from acatalasemic mice was significantly higher than those of normal mice. The results confirm that the reduction of mercuric ion to metallic mercury occurs by recycling of mercury in the tissues and reoxidized metallic mercury to mercuric ion by catalase. Mercuric ion was reduced to metallic mercury in the presence of superoxide anion in vitro. The reduction rate of mercuric ion to metallic mercury in the presence of both superoxide anion and cytochrome C or nitro blue tetrazolium was higher than that in the presence of superoxide anion alone, and the reduction of mercuric ion by NADPH or NADH was also observed. The reduction of mercuric ion to metallic mercury by liver homogenates of acatalasemic mice was higher than that of normal mice.

Using a new, synthetic whole-blood control and an improved reflectance meter, the within-run precision of Dextrostix Reagent Strips for quantitative determination of blood-glucose levels is compared with three common manual methods (hexokinase, o-toluidine, and glucose oxidase), and one automated method (neocuproine-AutoAnalyzer). In addition, the strip is compared on a day-to-day basis with the o-toluidine method. Dextrostix, used with the new instrument and control, provides results that compare very well with the other methods for within-run precision, and with the o-toluidine method for day-to-day results.

The administration of enzymes is of potential therapeutic value in many disease states, e.g. lysosomal storage diseases, provided problems in the metabolism and targeting of large proteins can be overcome. We have addressed ourselves to these problems by studying the pharmacokinetics and distribution of glucose-oxidase (GO) and some of its derivatives in mice. A saturable mechanism was responsible for GO uptake by mononuclear phagocytes. After construction of a pharmacokinetic model, the Kuptake (850 nmol/l) and the number of capturing cells were determined; uptake was half the initial plasma concentration in about 10 min. Deglycosylated GO's had half-lives of about 100 min and were taken up by the same organs that took up native GO. Galactosylated GO had a half-life of 4 min and a different distribution; it was taken up preferentially by the liver in hepatocytes. Our results illustrate the role sugars might play in the targeting of foreign proteins to different cell types, and the feasibility of determining in vivo microscopic constants such as the affinity between molecules and certain cells.

An electrochemical method for the quantitation of glucose oxidase in murine plasma and tissues has been developed. Instead of oxygen, this method uses benzoquinone as an artificial cosubstrate of glucose oxidase. The quantitative detection of the enzymatically produced hydroquinone by controlled-potential amperometry allows measurement of glucose oxidase concentrations in biological samples. The use of an internal standard corrects for all possible interfering effects. We demonstrated a 10-fold increase in sensitivity, as well as the ability to work in turbid media, in comparison to spectrophotometric methods.

The accuracy of a new reagent test strip (Chemstrip BG) for the quantitative estimation of whole blood glucose concentration was compared to that of a widely used test strip (Dextrostix). To perform the comparative study, venous blood specimens were obtained from 133 patients. Interpretations of reagent strip glucose readings were made by three observers who separately recorded their impressions from the two strips on each patient. These estimated levels were compared to quantitative (glucose oxidase) concentrations measured from the same specimen. Although there were significant correlations (p less than 0.001) between both reagent strips and the measured values, the Chemstrip BG results more closely approximately measured values for the range of glucose concentrations encountered (10-600 mg/dl). In addition, Chemstrip BG was easier to read and measured a wider range of values than Dextrostix and, unlike Dextrostix, Chemstrip BG strips could be stored for review at a later time. This new glucose test strip accurately and rapidly determines whole blood glucose concentration at the bedside.