Mussel-inspired enzyme immobilization and dual real-time compensation algorithms for durable and accurate continuous glucose monitoring.

Blood glucose sensing is very important for diabetic management. It is shifting towards a continuous glucose monitoring because such a system can alleviate patient suffering and provide a large number of glucose measurements. Here, we proposed a novel approach for the development of durable and accurate enzymatic continuous glucose monitoring system (CGMS). For the long-term durable and selective immobilization of glucose oxidase on a microneedle electrode, a biocompatible engineered mussel adhesive protein was employed through efficient electrochemical oxidation strategy. For the accurate performance in in vivo environments, we also suggested dual real-time compensated algorithms to cover both temperature and time-lag differences. After pre-clinical and pilot-clinical evaluations, we confirmed that our proposed CGMS has an outstanding performance compared with various commercially available continuous systems and achieves comparable performance to disposable glucose sensors.

A selective glucose sensor based on direct oxidation on a bimetal catalyst with a molecular imprinted polymer.

A selective nonenzymatic glucose sensor was developed based on the direct oxidation of glucose on hierarchical CuCo bimetal-coated with a glucose-imprinted polymer (GIP). Glucose was introduced into the GIP composed of Nafion and polyurethane along with aminophenyl boronic acid (APBA), which was formed on the bimetal electrode formed on a screen-printed electrode. The extraction of glucose from the GIP allowed for the selective permeation of glucose into the bimetal electrode surface for oxidation. The GIP-coated bimetal sensor probe was characterized using electrochemical and surface analytical methods. The GIP layer coated on the NaOH pre-treated bimetal electrode exhibited a dynamic range between 1.0µM and 25.0mM with a detection limit of 0.65±0.10µM in phosphate buffer solution (pH 7.4). The anodic responses of uric acid, acetaminophen, dopamine, ascorbic acid, L-cysteine, and other saccharides (monosaccharides: galactose, mannose, fructose, and xylose; disaccharides: sucrose, lactose, and maltose) were not detected using the GIP-coated bimetal sensor. The reliability of the sensor was evaluated by the determination of glucose in artificial and whole blood samples.

Disposable all-solid-state pH and glucose sensors based on conductive polymer covered hierarchical AuZn oxide.

Poly(terthiophene benzoic acid) (pTBA) layered-AuZn alloy oxide (AuZnOx) deposited on the screen printed carbon electrode (pTBA/AuZnOx/SPCE) was prepared to create a disposable all-solid-state pH sensor at first. Further, FAD-glucose oxidase (GOx) was immobilized onto the pTBA/AuZnOx/SPCE to fabricate a glucose sensor. The characterizations of the sensor probe reveal that AuZnOx forms a homogeneous hierarchical structure, and that the polymerized pTBA layer on the alloy oxide surface captures GOx covalently. The benzoic acid group of pTBA coated on the probe layer synergetically improved the pH response of the alloy oxide and provide chemical binding sites to enzyme, which resulted in a Nernstian behavior (59.2 ± 0.5 mV/pH) in the pH range of 2-13. The experimental parameters affecting the glucose analysis were studied in terms of pH, temperature, humidity, and interferences. The sensor exhibited a fast response time <1s and a dynamic range between 30 and 500 mg/dL glucose with a detection limit of 17.23 ± 0.32 mg/dL. The reliabilities of the disposable pH and glucose sensors were examined for biological samples.

Interference Reduction in Glucose Detection by Redox Potential Tuning: New Glucose Meter Development.

A new glucose meter was developed employing a novel disposable glucose sensor strip comprising a nicotinamide adenine dinucleotide-glucose dehydrogenase (NAD-GDH) and a mixture of Fe compounds as a mediator. An iron complex, 5-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)-1,10-phenanthroline iron(III) chloride (Fe-PhenTPy), was synthesized as a new mediator for the NAD-GDH system. Due to the high oxidation potential of the mediator, the detection potential was tuned to be more closely fitted toward the enzyme reaction potential, less than 400 mV (vs. Ag/AgCl), by mixing with an additional iron mediator. The impedance spectrometry for the enzyme sensor containing the mixed mediators showed an enhanced charge transfer property. In addition, a new cartridge-type glucose meter was manufactured using effective aligned-electrodes, which showed an enhanced response compared with conventional electrode alignment. The proposed glucose sensor resulted in a wide dynamic range in the concentration range of 30 - 500 mg dL(-1) with a reduced interference effect and a good sensitivity of 0.57 µA mM(-1).

Reliability of ultra-short-term analysis as a surrogate of standard 5-min analysis of heart rate variability.

BACKGROUND: Despite the increasing demands of ultra-short-term heart rate (HR) variability (HRV) for practical ambulatory applications, there have been few studies that have investigated R-R interval recording for less than 5 min for HRV analysis. It has not been extensively validated, and, currently, no normative data for ultra-short-term HRV exist. The aim of this study was to investigate the relationship between standard 5-min and ultra-short-term HRV by collecting data from a large population consisting of a wide range of age groups. MATERIALS AND METHODS: The 5-min R-R interval series were obtained from 467 healthy volunteers ranging from 8 to 69 years of age. The original R-R interval was segmented into 270, 240, 210, 180, 150, 120, 90, 60, 30, 20, and 10 s, and those HRV features most commonly reported within the literature were calculated and compared with those using the original 5-min R-R interval series. The Pearson correlation r, the p value by the Kruskal-Wallis test, and the Bland-Altman plot analysis computations were performed for each HRV variable calculated using different lengths of R-R interval series. RESULTS: For each HRV variable, the minimum length of the R-R interval required to reliably estimate the 5-min HRV was identified. The results were different for each age group: 10 s for HR, 20 s for high-frequency, 30 s for root mean square difference, 60 s for proportion of the number of interval differences of successive NN intervals greater than 50 ms divided by total number of NNs, 90 s for low-frequency, normalized low-frequency, normalized high-frequency, and low-frequency/high-frequency, 240 s for standard deviation of successive NN interval differences and time-frequency, and 270 s for very low-frequency. In addition, the reference value for short-term HRV from normal healthy subjects was also presented. CONCLUSIONS: Some HRV variables calculated from R-R interval series shorter than 5 min were well matched with those calculated from the 5-min R-R interval. Thus, ultra-short-term HRV is likely to be a good surrogate method to assess trends in HRV.

Electron-transfer mediator for a NAD-glucose dehydrogenase-based glucose sensor.

A new electron-transfer mediator, 5-[2,5-di (thiophen-2-yl)-1H-pyrrol-1-yl]-1,10-phenanthroline iron(III) chloride (FePhenTPy) oriented to the nicotinamide adenine dinucleotide-dependent-glucose dehydrogenase (NAD-GDH) system was synthesized through a Paal-Knorr condensation reaction. The structure of the mediator was confirmed by Fourier-transform infrared spectroscopy, proton and carbon nucler magnetic resonance spectroscopy, and mass spectroscopy, and its electron-transfer characteristic for a glucose sensor was investigated using voltammetry and impedance spectroscopy. A disposable amperometric glucose sensor with NAD-GDH was constructed with FePhenTPy as an electron-transfer mediator on a screen printed carbon electrode (SPCE) and its performance was evaluated, where the addition of reduces graphene oxide (RGO) to the mediator showed the enhanced sensor performance. The experimental parameters to affect the analytical performance and the stability of the proposed glucose sensor were optimized, and the sensor exhibited a dynamic range between 30 mg/dL and 600 mg/dL with the detection limit of 12.02 ± 0.6 mg/dL. In the real sample experiments, the interference effects by acetaminophen, ascorbic acid, dopamine, uric acid, caffeine, and other monosaccharides (fructose, lactose, mannose, and xylose) were completely avoided through coating the sensor surface with the Nafion film containing lead(IV) acetate. The reliability of proposed glucose sensor was evaluated by the determination of glucose in artificial blood and human whole blood samples.

5alpha-reductase inhibitory components as antiandrogens from herbal medicine.

We investigated medicinal plant sources with 5alpha-reductase inhibitory activity. These compounds have been used in several remedies against androgen-dependent diseases including benign prostatic hyperplasia. The 50% ethanol extract of Polygonum multiflorum Thunb (Polygoni Multiflori Radix; Polygonaceae) showed potent 5alpha-reductase inhibitory activity. The fraction responsible for this activity was purified, and the active constituent was isolated and identified as emodin, an anthraquinone compound. Although emodin showed considerably less potent inhibitory activity than riboflavin, the inhibitory activity of the compound was more potent than that of alizarin (1,2-dihydroxyanthraquinone), an anthraquinone-type positive control. Also, anthraquinone itself was substantially inactive against 5alpha-reductase, in dicating that the hydroxyl group on the structure of emodin is an important structural moiety for displaying inhibitory activity.

Detection of subjects with higher self-reporting stress scores using heart rate variability patterns during the day.

Heart rate variability (HRV) has been well established to measure instantaneous levels of mental stress. Circadian patterns of HRV features have been reported but their use to estimate levels of mental stress were not studied thoroughly. In this study, we investigated time dependent variations of HRV features to detect subjects under chronic mental stress. Sixty eight subjects were divided into high (n=10) and low stress group (n=43) depending on their self-reporting stress scores. HRV features were calculated during three different time periods of the day. High stress group showed decreased patterns of HRV features compared to low stress group. When logistic regression analysis was performed with raw multiple HRV features, the classification was 63.2% accurate. A new % deviance score reflecting the degree of difference from normal reference patterns increased the accuracy to 66.1%. Our data suggested that HRV patterns obtained at multiple time points of the day could provide useful data to monitor subjects under chronic stress.

Foreign body-induced actinomycosis mimicking bronchogenic carcinoma.

Actinomycosis is a slowly progressive infectious disease caused by an anaerobic and microaerophilic bacteria that colonizes the face, neck, lung, pleura and the ileocecal region. There have been a few cases of this disease which have involved in the lung but one very rare case has been reported. We report a case of foreign body-induced endobronchial actinomycosis mimicking bronchogenic carcinoma in a 69-year-old man. On admission, the patient presented with weight loss, cough and hemoptysis. The fiberoptic bronchoscopy revealed a soft tissue mass, with a partial occlusion of the left upper bronchus, which resembled bronchogenic carcinoma. Contrary to the first impression, the biopsy of the bronchus revealed the mass lesion to be an actinomycotic infection involving the bronchus. After the confirmation of the lesion, treatment with penicillin was initiated. The follow-up bronchoscopy revealed an aspirated fish bone at the site of infection. The foreign body was safely removed.

The Effects of Insulin-like Growth Factor-I (IGF-I) in Mouse Lung Cancer Cells.

PURPOSE: Insulin-like growth factor-I (IGF-I) is an important mitogen in many types of malignancies. The purpose of this study was to evaluate the role of the IGF system on cell proliferation and cell death in mouse lung cancer cell lines (3LL). MATERIALS AND METHODS: Northern analysis was performed in 3LL cells. We evaluated the phosphorylation of IGF-I receptor (IGF-IR) with IGF-I stimulation. MTT assay was performed after treating 3LL cells with IGF-I and the treatment effect on cell death in the presence of anticancer drug was investigated. RESULTS: Northern analysis revealed the presence of IGF-I and IGF-IR mRNA expression in 3LL cells. IGF-I increased cellular proliferation in serum free media. IGF-I also stimulated the tyrosine phosphorylation of two proteins: one, with a molecular mass of 95 kDa, was the beta-subunit of IGF-IR; the other, with an approximate molecular mass of 185 kDa, was originally identified as the insulin receptor substrate-I (IRS-I). IGF-I at a low concentration inhibited the cell death induced by adriamycin. CONCLUSION: IGF-I, a mitogen through the phosphorylation of the IGF-IR beta-subunit, acts as a survival factor to inhibit cell death. Therefore, these findings suggest that IGF-I and IGF-IR are involved in both the cell proliferation and cell death associated with cancer cell growth.