Bacterial Vaginosis Monitoring with Carbon Nanotube Field-Effect Transistors.

The ability to rapidly and reliably screen for bacterial vaginosis (BV) during pregnancy is of great significance for maternal health and pregnancy outcomes. In this proof-of-concept study, we demonstrated the potential of carbon nanotube field-effect transistors (NTFET) in the rapid diagnostics of BV with the sensing of BV-related factors such as pH and biogenic amines. The fabricated sensors showed good linearity to pH changes with a linear correlation coefficient of 0.99. The pH sensing performance was stable after more than one month of sensor storage. In addition, the sensor was able to classify BV-related biogenic amine-negative/positive samples with machine learning, utilizing different test strategies and algorithms, including linear discriminant analysis (LDA), support vector machine (SVM), and principal component analysis (PCA). The biogenic amine sample status could be well classified using a soft-margin SVM model with a validation accuracy of 87.5%. The accuracy could be further improved using a gold gate electrode for measurement, with accuracy higher than 90% in both LDA and SVM models. We also explored the sensing mechanisms and found that the change in NTFET off current was crucial for classification. The fabricated sensors successfully detect BV-related factors, demonstrating the competitive advantage of NTFET for point-of-care diagnostics of BV.

Modulation of advanced glycation end products by candesartan in patients with diabetic kidney disease--a dose-response relationship study.

Advanced glycation end products (AGEs) are proinflammatory mediators implicated in the pathogenesis of diabetic kidney disease (DKD). In this study, dose-dependent effects of angiotensin receptor blockade on urinary AGEs were evaluated in patients with DKD. Patients with type 2 diabetes and proteinuria ≥500 mg/d (n = 11) were compared with diabetic controls without DKD (n = 10) and normal controls (n = 11). After a 2-week washout period, DKD participants were treated with candesartan doses progressively increasing from 8, 16, 32, to 64 mg/d every 3 weeks for a total of 12 weeks. Other antihypertensive agents were adjusted to maintain stable blood pressure. At baseline and after each dosing period, blood pressure measurements and 24-hour urine collections were obtained. Urinary carboxymethyl lysine, an AGE biomarker, was reduced over the 12-week dose escalation protocol (r = 0.38, P = 0.01) in DKD participants. Creatinine clearance increased slightly, but albuminuria was unaffected by candesartan administration. Baseline urinary transforming growth factor-ß1 excretion was lower in DKD participants than in controls and did not change during the study period. Reducing kidney exposure to AGEs may be a mechanism of protection by angiotensin receptor blockade in DKD. AGEs may also impact the diabetic kidney through mechanisms independent of transforming growth factor-ß1.

Direct high-performance liquid chromatographic analysis of D-tocopheryl acid succinate and derivatives.

A method of analysis of a Vitamin E derivative D-tocopheryl acid succinate (TS) in biological fluids and commercially available products is necessary to study the kinetics of in vitro and in vivo metabolism, tissue distribution, and content uniformity. A simple and inexpensive high-performance liquid chromatographic method was developed for the direct determination of D-tocopheryl acid succinate in commercially available products, rat serum, and rat tissues. This method can also be applied to the determination of 15 Vitamin E derivatives. Rat serum (0.1 ml) was extracted with sodium dodecyl sulfate, ethanol, hexane, and then dried under nitrogen gas after addition of the internal standard, DL-alpha-tocopherol acetate. Separation was achieved on a C18 column with UV detection at 205 nm. The calibration curve for D-tocopheryl acid succinate was linear ranging from 0.025 to 100 microg/ml. The mean extraction efficiency was >92%. Precision of the assay was <5% (CV), and was within 5% at the limit of quantitation (0.025 microg/ml). Bias of the assay was lower than 5%, and was within 5% at the limit of quantitation. The assay was applied successfully to the serum and tissue distribution of D-tocopheryl acid succinate in rats, various Vitamin E derivatives, and content uniformity in commercially available products containing D-tocopheryl acid succinate.

Amino acids injure mesangial cells by advanced glycation end products, oxidative stress, and protein kinase C.

BACKGROUND: In diabetes, high intake of dietary protein exacerbates responses associated with kidney damage. Increased levels of amino acids could injure cells by providing free amino groups for glycation reactions leading to advanced glycation end products (AGEs). METHODS: Rat mesangial cells were cultured with increased amino acids designed to resemble protein feeding, high glucose (30.5 mmol/L), and, the combination, amino acids/high glucose. AGEs, reactive oxygen species (ROS), protein kinase C (PKC) activity and production, and mitogen-activated protein (MAP) kinase-extracellular signal regulated kinase (ERK) 1,2 activity were measured. Inhibitors were used to determine roles of these processes in fibrosis and/or AGE formation. RESULTS: AGE immunostaining increased when cells were cultured in amino acids and was comparable to that observed with high glucose. In amino acids/high glucose, AGE immunostaining appeared even greater. Amino acids, high glucose, and amino acids/high glucose induced ROS production. Aminoguanidine and vitamin E prevented AGE accumulation and induction of protein and mRNA for fibrosis markers [transforming growth factor-beta1 (TGF-beta1), fibronectin, and collagen IV]. PKC and ERK 1,2 activity increased with amino acids, high glucose, and amino acids/high glucose. PKC-beta inhibition prevented ERK 1,2 activation and fibrosis induction. ERK 1,2 inhibition also blocked the fibrosis response. CONCLUSION: A profibrotic injury response occurred in mesangial cells exposed to amino acids, with or without high glucose, by formation of AGE, oxidative stress, and activation of the PKC-beta and MAP kinase-ERK 1,2 signal pathway. These observations provide new insight into cellular mechanisms of kidney damage produced by excess dietary protein, particularly in diabetes.

Chemopreventive effect of dietary d-alpha-tocopheryl succinate supplementation on precancer colon aberrant crypt formation and vitamin E analogue levels in young and old rats.

This study examined the effects of dietary d-alpha-tocopheryl succinate (TS) in female rats, 20 mo (OLD) or 2 mo (YNG) of age, on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and tissue distribution of d-alpha-tocopherol (alphaT), d-gamma-tocopherol (gammaT), and alphaTS. Rats were fed a commercial rodent chow supplemented with or without 1 (YNG) or 2 (OLD) g alphaTS/kg diet for 1 week prior to ip administration of AOM to induce colon ACF. The animals were sacrificed after 49 days of exposure. The results showed that OLD rats had significantly fewer ACF than YNG animals, and the percent body fat and serum triglycerides were significantly higher in the OLD group compared with the YNG. However, only OLD animals receiving alphaTS had significantly reduced numbers of larger ACF and significantly higher levels of colonic alphaT, gammaT, and alphaTS. These data support previous studies demonstrating that dietary alphaTS administration is protective against intestinal cancer. Also, this is the first study to show that alphaTS accumulates in most tissues following dietary exposure. We hypothesize that increased colon accumulation of fat-soluble vitamin E compounds and subsequent chemoprevention may be related to greater percent body fat and serum triglycerides in OLD animals receiving dietary TS.

Provision of pharmacy services to underserved populations via remote dispensing and two-way videoconferencing.

A telepharmacy program aimed to resolve the dual problem of access to prescription drugs and pharmacists for low-income populations is described. The program was conducted at the Community Health Association of Spokane (CHAS), a federally qualified community health center, and initiated in January 2001. The program, known as Telepharmacy at CHAS, allows for the dispensing of low-cost medications through participation in the federal government's 340B program and use of remote dispensing and counseling via a two-way interactive videoconferencing system to patients at six urban and rural clinics. The regulatory and practical steps necessary to implement and maintain the program are also presented. Consecutive patients whose prescriptions were filled at the base site or remote-sites were invited to complete a pharmacy satisfaction questionnaire during a two-week period in March 2003. Over the two-week period, 93 patients seen at remote sites and 106 seen at the base site completed the questionnaire. Over 75% of patients seen at the remote sites were satisfied with their videoconference interactions with the pharmacist. Of the patients seen at the base site, 66% agreed or strongly agreed that they were satisfied with the time required to obtain medications and counseling. A high percentage of patients at both the base site (94%) and remote sites (63%) strongly agreed or agreed that they would have difficulty affording their medications without this program. Telepharmacy at CHAS has been well received by most of the patients and improved their access to medications and pharmacy services.