Effect of serotonin transporter genotype on self-reported efficacy and activity changes of brain prefrontal area in response to placebo.

Patients benefit from drug therapy not only through pharmacological mechanisms, but also through non-pharmacological action (placebo effect), which may be mediated in part by the prefrontal area of the brain. We consider that the difference between responders and non-responders to placebo might be related to polymorphisms in the serotonin transporter-linked polymorphic region (5-HTTLPR). To study this idea, we performed a randomized double-blind clinical trial using caffeine and lactose (placebo). Activity in the prefrontal area of the brain was measured in terms of blood flow by means of near-infrared spectroscopy (NIRS) as an objective indicator. Self-reported feelings of drowsiness on established scales were used as subjective indicators. Twenty-one subjects in block A took caffeine on the first day and placebo on the third day, and 21 in block B took placebo on the first day and placebo on the third day. After placebo administration, improvement of sleepiness was significantly enhanced, a similar extent to that after caffeine medication. Among the 42 subjects, 22 showed S/S type polymorphism in the serotonin transporter (52.4 %), 17 showed S/L type (40.5 %) and 3 showed L/L type (7.10 %). Statistical analysis of the results indicate that subjects with L/L genotype showed a significantly greater placebo response in terms of both self-reported feeling of drowsiness and blood flow in the prefrontal area of the brain associated with working memory (46 area). Our results indicate that the L/L genotype of 5-HTTLPR, which is rare in Japanese (3.2 %) but common in Americans (32.2 %), may be associated with a greater placebo effect.

Flow-dependent concentration polarization of plasma proteins at the luminal surface of a cultured endothelial cell monolayer.

Flow-dependent concentration or depletion of atherogenic low density lipoproteins which has been theoretically predicted to occur at a blood/endothelium boundary may play an important role in the genesis, progression, and regression of atherosclerosis in man and intimal hyperplasia in vascular grafts implanted in the arterial system in man and experimental animals. Hence to explore such a possibility, we have studied the effect of a steady shear flow on concentration polarization of plasma proteins and lipoproteins at the luminal surface of a cultured bovine aortic endothelial cell (BAEC) monolayer which served as a model of the vessel wall of an artery or an implanted vascular graft. The study was carried out by circulating a cell culture medium containing fetal calf serum or bovine plasma lipoproteins in steady flow through a parallel-plate flow cell in which a cultured BAEC monolayer was installed, over the physiologic ranges of wall shear rate and water filtration velocity at the BAEC monolayer. The water (cell culture medium) filtration velocity at the BAEC monolayer was determined to provide a measure of the change in concentration of plasma protein particles at the luminal surface of the BAEC monolayer. It was found that for perfusates containing plasma proteins and/or lipoproteins, water filtration velocity varied as a function of flow rate, being lowest in the absence of flow. Water filtration velocity increased or decreased as flow rate increased or decreased from an arbitrarily set non-zero value, indicating that surface concentration of protein particles varied as a direct function of flow rate, and the process was reversible. It was also found that at particle concentrations equivalent to those found in a culture medium containing serum at 20% by volume, plasma lipoproteins which were much smaller in number and lower in concentration but larger in size than albumin, showed almost the same effect as observed with serum which contained both lipoproteins and albumin, indicating that the substance responsible for this phenomenon is not albumin but lipoprotein whose diffusivity is much smaller than that of albumin. The results strongly support our hypothesis that flow-dependent concentration polarization of lipoproteins occurs at a blood endothelium boundary, and this in turn promote the localization of various vascular diseases which develop in our arterial system.

The promise of automated wellness systems.

Do automated wellness programs hold out the promise of improving the health of individuals and populations through the establishment of baseline wellness checkpoints? Nurse case managers have a strong interest in this question. The automation of wellness programs and the integration of this information into the continuum of a care information system model offers ongoing, interactive accountability of individual health status. The crowning glory will be the ultimate integration of the individual's personal health game plan with the provider's continuum of care offering. The strength of the nursing profession lies in its traditional role of promoting health through preventive measures (public health nursing) and managing the ill patient's progress toward his/her optimal health status. Therefore, nurses and nurse case managers should embrace wellness programs and wellness data availability. Because of their experience in using and understanding wellness data, nurses are in a unique position. Not only will they be able to assimilate rapidly the use of wellness data into their own practice, they also will be able to guide other professionals in its use. The table in this articles provides examples of the impact that automated wellness program data could have at various stages of the clinical decision-making process.

Effect of pH on the kinetics of bovine liver glutamate dehydrogenase self-association.

The temperature-jump technique with light-scattering detection was applied to the kinetic study on the self-association of bovine liver glutamate dehydrogenase (EC 1.4.1.3). The measurements were carried out for systems in phosphate buffer of differing pH, 6.3-7.8, and of differing phosphate concentration at 11.5 degrees C. The observed association rate constant decreased with increasing phosphate concentration at the respective pH values. This observation was interpreted in terms of the inhibition from self-association by specific binding of phosphate ion to the protein. According to this interpretation, the intrinsic association rate constant, k(0)a, and the binding constant of phosphate ion, Kp, were estimated. k(0)a varied with pH in a manner as described by a titration curve with pK of about 7, while Kp remained almost constant in the pH range studied.

Subunit dissociation and unfolding of bovine liver glutamate dehydrogenase induced by guanidine hydrochloride.

Equilibrium and kinetic measurements were carried out on the denaturation of bovine liver glutamate dehydrogenase (L-glutamate:NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3) induced by guanidine hydrochloride (Gdn-HCl) in 0.2 M phosphate buffer (pH 7.3) using two types of detection, light-scattering and circular dichroism. The results obtained in equilibrium studies showed that the enzyme exists in solution as hexamers of native subunit at Gdn-HCl concentrations below 0.6 M, as trimers of native subunit in the concentration range between 1.0 and 2.0 M, and as monomers with unfolded structure above 2.8 M. From the kinetic studies, it was found that the dissociation of hexamer to trimer takes place more rapidly than that of trimer to monomer by a factor of 10, and it was also found that the unfolding of the polypeptide chain occurs much more slowly than subunit dissociation.

Effect of phosphate concentration on the kinetics of bovine liver glutamate dehydrogenase self-association.

The kinetics of the self-association of bovine liver glutamate dehydrogenase was studied at various phosphate buffer concentrations (pH 7.3) at 11.5 degrees C by means of the temperature-jump technique with scattered light detection. The observed relaxation times were well explained by the random association model of Thusius et al. With increasing phosphate concentration, the association rate constant derived from the model decreased, while the dissociation rate constant was left almost constant. Relaxation amplitude was also dependent on the phosphate concentration. The changes in the rate constant and relaxation amplitude with phosphate concentration are well elucidated by assuming that glutamate dehydrogenase is protected from association by specific masking of the association site by phosphate ions.