Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.     

New Insights into the Appraisal of Flood-Alleviation Benefits: (1) Flood Damage and Flood Loss Information

New approaches to the appraisal of flood-alleviation investment have been developed over the last twenty-five years. This has led to (a) increased precision in benefit-cost analysis, as better data have become available, and (b) a more rational approach to decision making as the UK Government has clarified and enhanced the decision criteria. This paper presents a detailed account of some of these developments, with an emphasis on the data on flood damages and losses avoided by flood-alleviation schemes, and draws out lessons for those involved in this form of investment appraisal.     

Refactoring Tools: Fitness for Purpose

Refactoring tools can improve the speed and accuracy with which developers create and maintain software—but only if they are used. In practice, tools are not used as much as they could be; this seems to be because sometimes they do not align with the refactoring tactic preferred by most programmers, a tactic the authors call "floss refactoring." They propose five principles that characterize successful floss-refactoring tools—principles that can help programmers to choose the most appropriate refactoring tools and also help toolsmiths to design tools that fit the programmer's purpose.     

Articulated hybrid mobile robot mechanism with compounded mobility and manipulation and on-board wireless sensor/actuator control interfaces

This paper presents the development of a remotely operated mobile robot system with a hybrid mechanism whereby the locomotion platform and manipulator arm are designed as one entity to support both locomotion and manipulation interchangeably. The mechanical design is briefly described as well as the dynamic simulations used to analyze the robot mobility and functionality. As part of the development, this paper mainly focuses on a new generalized control hardware architecture based on embedded on-board wireless communication network between the robot’s subsystems. This approach results in a modular control hardware architecture since no wire connections are used between the actuators and sensors in each of the mobile robot subsystems and also provides operational fault-tolerance. The effectiveness of this approach is experimentally demonstrated and validated by implementing it in the hybrid mobile robot system. The new control hardware architecture and mechanical design demonstrate the qualitative and quantitative performance improvements of the mobile robot in terms of the new locomotion and manipulation capabilities it provides. Experimental results are presented to demonstrate new operative tasks that the robot was able to accomplish, such as traversing challenging obstacles, and manipulating objects of various capacities; functions often required in various challenging applications, such as search and rescue missions, hazardous site inspections, and planetary explorations.     

Design of Multiresponsive Hydrogel Particles and Assemblies

In the realm of soft nanotechnology, hydrogel micro‐ and nanoparticles represent a versatile class of responsive materials. Over the last decade, our group has investigated the synthesis and physicochemical properties of a variety of synthetic hydrogel particles. From these efforts, several particle types have emerged with potentially enabling features for biological applications, including nanogels for targeted drug delivery, microlenses for biosensing, and coatings for biomedical devices. For example, core/shell nanogels have been used to encapsulate and deliver small interfering RNA to ovarian cancer cells; nanogels used in this fashion may improve therapeutic outcomes for a variety of macromolecular therapeutics. Microgels arranged as multilayers on implantable biomaterials greatly minimize the host inflammatory response to the material. Furthermore, the triggered release of drugs (i.e., insulin) has been demonstrated from similar assemblies. The goal of this feature article is to highlight developments in the design of responsive microgels and nanogels in the context of our recent efforts and in relation to the community that has grown up around this fascinating class of materials.     

Investigating polysilicon thin film structural changes during rapid thermal annealing of a thin film crystalline silicon on glass solar cell

Structural changes resulting from rapid thermal annealing were investigated in a thin film crystalline silicon on textured glass solar cell, in particular grain parameters and film modulus. Electron backscatter diffraction showed no significant change in grain dimensions post annealing and no preferred orientation. Columnar grains with large defect densities were visible in transmission electron microscopy with no qualitative change visible post annealing. A similar modulus obtained by nanoindenation, both pre and post annealing suggests no quantitative structural change. The film structure appears unchanged by rapid thermal annealing.     

Comparison of the group V and VI transition metal carbides for methane dry reforming and thermodynamic prediction of their relative stabilities

The DME‐SCR activity was suppressed upon exposure of a γ-alumina catalyst to SO₂, in contrast to methanol‐SCR, which remains active at the same surface sulphate coverage. This difference in behaviour is attributed to the limited availability of surface methoxy, which may be regarded as a prerequisite for NOx- reduction over γ-alumina under lean conditions, in the case of dimethyl ether in the presence of SO₂. This revised version was published online in July 2006 with corrections to the Cover Date.