Optical Fibers Functionalized with Single-Walled Carbon Nanotubes for Flexible Fluorescent Catecholamine Detection.

Despite the blockbuster popularity of drugs that act on catecholamine receptors, catecholamine dynamics in human health and disease remain an incomplete picture. Recent advances in fluorescent sensors have enabled unprecedented access to catecholamine dynamics in preclinical animal models, but the requirements of these technologies limit translational value for clinical diagnostics. Here, we present a flexible and convenient tool for fluorescent catecholamine detection by functionalizing optical fibers with single-walled carbon nanotube (SWNT)-based near-infrared catecholamine sensors (nIRCats), a form factor that has potential for more convenient and less invasive clinical translation. We show that these near-infrared functionalized (nIRF) fibers respond to dopamine in a biologically-relevant concentration range (10nM through 1 µM) with a mean ΔF/F0 of 0.022 through 0.411, with no statistically significant effect on signal magnitude after 16-hour exposure to human blood plasma. We further demonstrate the utility of these fibers in as little as 10 µL volumes of clinically relevant biofluids up to 24 weeks after preparation, with a ΔF/F0 of up to 0.059 through 1.127 for 10 nM through 1 µM dopamine. We also introduce a compact, mobile dual-near-infrared fiber photometry rig and demonstrate its success detecting dopamine with 0.005 ΔF/F0 in acute brain slices with nIRF fibers. Together, this fiber-based tool and photometry rig expand the toolbox of catecholamine detection technologies to a broader range of applications.

Uptake of newly introduced universal BCG vaccination in newborns.

Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

Posttreatment exacerbation of hepatitis B virus (HBV) infection in long-term HBV trials of emtricitabine.

Posttreatment exacerbation of hepatitis B virus (HBV) infection in long-term HBV trials of emtricitabine occurred in 23% of patients. Development of antibody to hepatitis e antigen did not prevent hepatic flare. One patient with marked bridging fibrosis required liver transplantation. Patients with advanced liver disease are at risk for hepatic flare with decompensation if active treatment is withdrawn (e.g., when highly active antiretroviral treatment is modified).

Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection.

A multicenter, open-label study was performed to evaluate the safety, anti-hepatitis B virus (anti-HBV) activity, and pharmacokinetics of emtricitabine therapy administered once daily for 8 weeks to patients infected with HBV. Clinical and virologic evaluations were completed at the baseline; at 7, 14, 28, 42, and 56 days during treatment; and at 24, 48, and 28 days posttreatment. Forty-nine patients were enrolled in five dose cohorts (doses of 25, 50, 100, 200, and 300 mg, all of which were administered once daily [q.d.]). Peak plasma emtricitabine concentrations occurred within 1.5 h following dosing. Plasma emtricitabine concentrations (maximum concentrations of drug in plasma and areas under the concentration-time curves) increased nearly dose proportionally over the 25- to 300-mg dose range, with relatively small intersubject variabilities. The plasma half-life of emtricitabine ranged from 6 to 9 h. HBV DNA levels were measured by the Digene HBV Hybrid Capture II assay. Viral suppression (reduction in log(10) serum HBV DNA levels) occurred in all dose cohorts. All doses demonstrated potent and rapid antiviral activities, with a trend toward a greater suppression with daily doses of 100 mg or greater. At 2 months, the median change in the serum HBV DNA level from the baseline level ranged from -1.7 log(10) for the 25-mg dose administered q.d. to -3.3 log(10) for the 300 mg dose administered q.d. Emtricitabine was well tolerated over the 2-month dosing period. These results support further clinical development of emtricitabine for the treatment of chronic hepatitis B infection.