5-hydroxytryptamine and depression: studies using a neuroendocrine strategy

S-Hydroxytryptamine and depression; studies using a neuroendocrine strategy I M Anderson BA MB.BS MA MRCP(UK) MRCPsych The syndrome of depression is a common psychiatric disorder with considerable morbidity and mortality. Brain pathways involving 5-hydroxytryptamine (5-HT) are likely to form part of the biological substrate for mood and there is now considerable evidence that depressed patients have abnormalities in measures of 5-HT function. However the nature of the 5-HT abnormality and its relationship to clinical features and to potentially confounding factors such as weight loss remain unknown. The present studies use a neuroendocrine challenge strategy to investigate aspects of 5-HT function related to depression. First, I study the effect of weight loss in normal volunteers and demonstrate that moderate weight loss through dieting lowers the plasma availability of the 5-HT precursor, L-tryptophan (TRP) in both sexes and that in women, but not men, brain 5-HT function, as measured by the prolactin (PRL) response to TRP, is altered. Second, I demonstrate that whereas the PRL response to infusion of the 5-HT uptake inhibitor, clomipramine, may provide an index of brain 5-HT function, its propensity to cause stressful side-effects warrants caution in interpretation of results. Using this challenge I show that depressed patients have blunted PRL responses compared to controls, particularly if they have features of melancholia, have attempted suicide or lost weight. This finding is not simply a reflection of impaired PRL secretion as I demonstrate that the PRL response to the dopamine antagonist, metoclopramide, is not altered in depression. Third, I investigate the hormone and temperature effects of a 5-HT1A agonist, gepirone, in normal volunteers and show that it may prove a useful tool in assessing the function of this 5-HT receptor subtype in humans. The implications of these studies are discussed. Weight loss is a potential confound for investigations of 5-HT function in depressed patients and may itself alter brain 5-HT function. This has implications for findings in depressed patients and for understanding the effects of dieting and the aetiology of eating disorders. The patient studies are consistent with, and add weight to, a substantial body of research showing decreased 5-HT function in depression although at present the site of the abnormality is not known. Use of specific 5-HT agonists, such as gepirone, will allow the investigation of 5-HT receptor subtype function in humans and will help to identify the nature of the 5-HT abnormality in depression

Secondary Ion Mass Spectrometry And Its Application To Studies In Geochemistry

Secondary ion mass spectrometry (SIMS) with specimen isolation conditions (an extreme form of energy filtering) is useful in geochemical studies. The presence of molecular ion interferences in SIMS spectra is greatly reduced when analyzing high energy secondary ions (i.e. specimen isolation conditions), thus simplifying the interpretation of mass spectra.;High energy secondary ions were found to be less susceptible to the dramatic changes in ionization yield resulting from the effect of the matrix in secondary ion production. Correlation of ion intensities for glass and crystalline materials of identical composition is possible for most elements when using some form of energy filtering, and thus the use of glass standards for SIMS analysis of minerals is possible. Some matrix effects are still present in the high energy ion population. However, in a given concentration range with a reliable set of standards, quantitative analysis down to the ppm level is available with specimen isolation or conventional energy filtering methods. This has been demonstrated for the rare-earth elements at both trace and major element concentration levels in various mineral grains.;The ionization probability of high energy ions was studied as a function of kinetic energy, first ionization potential, and oxide bond strength. A simple mechanism for the production of high energy secondary ions could not be obtained from these results.;Besides the elimination of molecular ion interferences, the method of specimen isolation is an excellent technique for the analysis of non-conducting samples. Leached, or altered zones up to several hundreds of angstroms in thickness have been observed in SIMS depth profiles of naturally and laboratory dissolved plagioclase. Dissolution of plagioclase in relatively simple laboratory experiments (pH 3.5 and 5.7) forms altered zones depleted of sodium, calcium and aluminum, and enriched (residually) in silicon. For specimens undergoing a more complex set of reactions (dissolution in nature), layers enriched in aluminum were observed in the SIMS profiles. Each of these layers are believed to form during the dissolution process. Qualitatively similar results were obtained using X-ray photoelectron spectroscopy, while SEM analysis has shown the sample surfaces to be clean and free of secondary precipitates

Design of a high performance soft x-ray emission spectrometer for the REIXS beamline at the Canadian Light Source

The optical design of a soft X-ray (90-1100~eV) emission spectrometer for the Resonant Elastic and Inelastic X-ray Scattering (REIXS) beamline to be implemented at the CLS is presented. An overview of soft X-ray optical theory as it relates to diffraction gratings is given. The initial constraints and the process that led to this design are outlined. Techniques and software tools that were developed, using ray-tracing and diffraction grating efficiency calculations, are discussed. The analysis completed with these tools to compare existing soft X-ray emission spectrometer designs is presented. Based on this analysis, a new design with superior performance for this application is proposed and reviewed. This design employs Rowland circle geometry to achieve a resolving power in excess of 2,500 in the range of interest. In addition, a novel design is proposed for a larger extremely high resolution spectrometer which will provide resolving powers exceeding 10,000 throughout the higher end of this range. A review is given of research into the components, manufacturing techniques and tolerances that will be required to produce this spectrometer

Studies on the photocatalytic activity of titanium dioxide

A novel technique for determining the photoactivity of anatase and rutile forms of TiO₂ has been developed. This involves measurement of the rate of oxygen-uptake in the propan-2-ol/propanone dehydrogenation system, which is photocatalysed by TiO₂ particles maintained in suspension. The system has been studied under several experimental conditions, including the variation of incident light intensity and sample temperature. The effect of varying the alcohol concentration on the oxygen-uptake rate has been studied and, found to be related to the self-association properties of the alcohol, as determined from a series of NMR studies. In addition, strong organic bases have been shown to be effective in reducing the oxygen-uptake rate and a mechanism involving the blocking of surface sites on TiO₂ is proposed. The generation and participation H₂O₂ of in the alcohol to ketone conversion has been studied and, in particular, a technique has been developed to enable the luminescence, which has been observed to emanate from the vortex of the irradiated suspension, to be studied under various experimental conditions. This technique revealed the rapid nature of the interaction of H₂O₂ at the TiO₂ surface. The overall mechanism of the photocatalysed dehydrogenation is discussed in terms of two interdependent pathways: one involving oxygen, the other H₂O₂. Photoluminescence from dry, powdered samples of anatase and rutile has been observed at low temperatures upon excitation with a pulsed nitrogen laser. The decay kinetics of the photoluminesoence have been modelled via computer fitting techniques and the participation of two sets of trapping sites is postulated for anatase and rutile. The photophysical behaviour of benzophenone in poly(methylmethacrylate) films has been studied and a dual pathway for triplet deactivation, involving delayed fluorescence and triplet-triplet annihilation put forward

Assessing the impacts of the first year of rotavirus vaccination in the United Kingdom

The United Kingdom (UK) added rotavirus (RV) vaccine (Rotarix GlaxoSmithKline) to the national vaccine schedule in July 2013. During the 2012–2014 rotavirus seasons, children presenting to the Bristol Royal Hospital for Children Emergency Department with gastroenteritis symptoms had stool virology analysis (real-time PCR) and clinical outcome recorded. Nosocomial cases were identified as patients with non-gastroenteritis diagnosis testing positive for rotavirus > 48h after admission. In comparison to average pre-vaccine seasons, in the first year after vaccine introduction there were 48% fewer attendances diagnosed with gastroenteritis, 53% reduction in gastroenteritis admissions and a total saving of 330 bed-days occupancy. There was an overall reduction in number of rotavirus-positive stool samples with 94% reduction in children aged under one year and a 65% reduction in those too old to have been vaccinated. In the first year after the introduction of universal vaccination against rotavirus we observed a profound reduction in gastroenteritis presentations and admissions with a substantial possible herd effect seen in older children. Extrapolating these findings to the UK population we estimate secondary healthcare savings in the first year of ca £7.5 (€10.5) million. Ongoing surveillance will be required to determine the long-term impact of the RV immunisation programme

Long term improvements in activities of daily living in patients with hemispatial neglect

No abstract available

A counterintuitive stereochemical outcome from a chelation-controlled vinylmetal aldehyde addition leads to the configurational reassignment of phormidolide A.

As part of our ongoing studies towards the total synthesis of phormidolide A (1), we explored the chelation-controlled vinylmetal addition of iodide 2 to aldehyde 3 to install the reported 17S configuration. While the stereochemical outcome of this reaction was opposite to that expected, detailed NMR comparisons with the previously reported triacetonide derivative of phormidolide A (18) highlighted that the major adduct was a better match to the natural product. The synthesis of three model acetonides and detailed spectroscopic comparisons to the triacetonide derivative of phormidolide A supports a reassignment of seven of the 11 stereocentres in phormidolide A (1a)

Population density profiles of nasopharyngeal carriage of 5 bacterial species in pre-school children measured using quantitative PCR offer potential insights into the dynamics of transmission.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBacterial vaccines can reduce carriage rates. Colonization is usually a binary endpoint. Real time quantitative PCR (qPCR) can quantify bacterial DNA in mucosal samples over a wide range. Using culture and single-gene species-specific qPCRs for Streptococcus pneumoniae (lytA), Streptococcus pyogenes (ntpC), Moraxella catarrhalis (ompJ), Haemophilus influenzae (hdp) and Staphylococcus aureus (nuc) and standard curves against log-phase reference strain broth cultures we described frequency and peak density distributions of carriage in nasopharyngeal swabs from 161 healthy 2-4 y old children collected into STGG broth. In general, detection by qPCR and culture was consistent. Discordance mostly occurred at lower detection thresholds of both methods, although PCR assays for S. pyogenes and S. aureus were less sensitive. Density varied across 5-7 orders of magnitude for the 5 species with the abundant species skewed toward high values (modes: S. pneumoniae log3-4, M. catarrhalis & H. influenzae log4-5 CFU/ml broth). Wide ranges of bacterial DNA concentrations in healthy children carrying these bacteria could mean that different individuals at different times vary greatly in infectiousness. Understanding the host, microbial and environmental determinants of colonization density will permit more accurate prediction of vaccine effectiveness.ESPID research fellowshi

The Effects of LAIV on Nasopharyngeal Bacteria in Healthy 2-4 Year Olds:a Randomized Controlled Trial

Rationale: Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria. Changes in the bacterial niche could affect transmission dynamics. Attenuated vaccine viruses can be used to investigate this empirically in humans. Objectives: To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine (LAIV) as a surrogate. Methods: We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Staphylococcus aureus. A total of 151 healthy children were randomized 1:1 to receive the vaccine starting either at recruitment (n = 74) or 28 days later (n = 77) in a stepped wedge fashion, allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination. Bacterial carriage and density were determined using quantitative polymerase chain reaction assays. Measurements and Main Results: A total of 151 children were recruited, 77 in the LAIV group and 74 in the control group. LAIV recipients (n = 63 analyzed) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls (n = 72 analyzed). S. pneumoniae density was substantially higher in vaccine recipients (16,687 vs. 1935 gene copies per milliliter) 28 days after the first dose (P < 0.001). Whole-group multivariable analysis (prevaccine, after one dose, and after two doses) also showed increases in density of other species and H. influenzae carriage prevalence. Conclusions: In the absence of any safety signals despite widespread use of the vaccine, these findings suggest that bacterial density, and thus transmission rates among children and to people in other age groups, may rise following attenuated influenza infections without associated clinical disease. LAIV could therefore be used as an experimental tool to elucidate the dynamics of transmission of nasopharyngeal bacteria