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      International Journal of Nanomedicine (submit here)

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      Simultaneous, noninvasive, and transdermal extraction of urea and homocysteine by reverse iontophoresis

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          Abstract

          Background:

          Cardiovascular and kidney diseases are a global public health problem and impose a huge economic burden on health care services. Homocysteine, an amino acid, is associated with coronary heart disease, while urea is a harmful metabolic substance which can be used to reflect kidney function. Monitoring of these two substances is therefore very important. This in vitro study aimed to determine whether homocysteine is extractable transdermally and noninvasively, and whether homocysteine and urea can be extracted simultaneously by reverse iontophoresis.

          Methods:

          A diffusion cell incorporated with porcine skin was used for all experiments with the application of a direct current (dc) and four different symmetrical biphasic direct currents (SBdc) for 12 minutes via Ag/AgCl electrodes. The dc and the SBdc had a current density of 0.3 mA/cm 2.

          Results:

          The SBdc has four different phase durations of 15 sec, 30 sec, 60 sec, and 180 sec. It was found that homocysteine can be transdermally extracted by reverse iontophoresis. Simultaneous extraction of homocysteine and urea by reverse iontophoresis is also possible.

          Conclusion:

          These results suggest that extraction of homocysteine and urea by SBdc are phase duration-dependent, and the optimum mode for simultaneous homocysteine and urea extraction is the SBdc with the phase duration of 60 sec.

          Most cited references25

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          Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.

          The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. Post hoc analysis. The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. 980 patients with mild renal insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration 0.2 for the difference). In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.
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            A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians.

            To assess prospectively the risk of coronary heart disease associated with elevated plasma levels of homocyst(e)ine. Nested case-control study using prospectively collected blood samples. Participants in the Physicians' Health Study. A total of 14,916 male physicians, aged 40 to 84 years, with no prior myocardial infarction (MI) or stroke provided plasma samples at baseline and were followed up for 5 years. Samples from 271 men who subsequently developed MI were analyzed for homocyst(e)ine levels together with paired controls, matched by age and smoking. Acute MI or death due to coronary disease. Levels of homocyst(e)ine were higher in cases than in controls (11.1 +/- 4.0 [SD] vs 10.5 +/- 2.8 nmol/mL; P = .03). The difference was attributable to an excess of high values among men who later had MIs. The relative risk for the highest 5% vs the bottom 90% of homocyst(e)ine levels was 3.1 (95% confidence interval, 1.4 to 6.9; P = .005). After additional adjustment for diabetes, hypertension, aspirin assignment, Quetelet's Index, and total/high-density lipoprotein cholesterol, this relative risk was 3.4 (95% confidence interval, 1.3 to 8.8) (P = .01). Thirteen controls and 31 cases (11%) had values above the 95th percentile of the controls. Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors. Because high levels can often be easily treated with vitamin supplements, homocyst(e)ine may be an independent, modifiable risk factor.
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              Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes.

              A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was -0.01 and 0.26 mmol l(-1) for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l(-1) for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l(-1) h(-1), which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.
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                Author and article information

                Journal
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2011
                2011
                20 February 2011
                : 6
                : 417-423
                Affiliations
                [1 ]Graduate Institute of Biomedicine and Biomedical Technology;
                [2 ]Department of Electrical Engineering, National Chi Nan University, Nantou, Taiwan;
                [3 ]Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan, Republic of China
                Author notes
                Correspondence: Congo Tak-Shing Ching, Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, No 1 University Rd, Puli, Nantou County 54561, Taiwan, Republic of China, Tel +886 4929 10960 ext 4774, Fax +886 4929 12434, Email tsching@ 123456ncnu.edu.tw
                Article
                ijn-6-417
                10.2147/IJN.S16418
                3075907
                21499431
                0f838975-7d15-4229-bc72-da1698ae9133
                © 2011 Ching et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 19 February 2011
                Categories
                Original Research

                Molecular medicine
                reverse iontophoresis,homocysteine,urea,monitoring,noninvasive,transdermal
                Molecular medicine
                reverse iontophoresis, homocysteine, urea, monitoring, noninvasive, transdermal

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