A complex relationship among chemical concentration, detection threshold and suprathreshold intensity of bitter compounds

Detection thresholds and psychophysical curves were established for caffeine, quinine-HCl (QHCl), and propylthiouracil (PROP) in a sample of 33 subjects (28 female mean age 24 &plusmn; 4). The mean detection threshold (&plusmn;standard error) for caffeine, QHCl, and PROP was 1.2 &plusmn; 0.12, 0.0083 &plusmn; 0.001, and 0.088 &plusmn; 0.07 mM, respectively. Pearson product&ndash;moment analysis revealed no significant correlations between detection thresholds of the compounds. Psychophysical curves were constructed for each bitter compound over 6 concentrations. There were significant correlations between incremental points of the individual psychophysical curves for QHCl and PROP. Regarding caffeine, there was a specific concentration (6 mM) below and above which the incremental steps in bitterness were correlated. Between compounds, analysis of psychophysical curves revealed no correlations with PROP, but there were significant correlations between the bitterness of caffeine and QHCl at higher concentrations on the psychophysical curve (P &lt; 0.05). Correlation analysis of detection threshold and suprathreshold intensity within a compound revealed a significant correlation between PROP threshold and suprathreshold intensity (r = 0.46&ndash;0.4, P &lt; 0.05), a significant negative correlation for QHCl (r = &ndash;0.33 to &ndash;0.4, P &lt; 0.05), and no correlation for caffeine. The results suggest a complex relationship between chemical concentration, detection threshold, and suprathreshold intensity.<br /

Structural effects and potential changes in growth factor signalling in penis-projecting autonomic neurons after axotomy

BACKGROUND: The responses of adult parasympathetic ganglion neurons to injury and the neurotrophic mechanisms underlying their axonal regeneration are poorly understood. This is especially relevant to penis-projecting parasympathetic neurons, which are vulnerable to injury during pelvic surgery such as prostatectomy. We investigated the changes in pelvic ganglia of adult male rats in the first week after unilateral cavernous (penile) nerve axotomy (cut or crush lesions). In some experiments FluoroGold was injected into the penis seven days prior to injury to allow later identification of penis-projecting neurons. Neurturin and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors for penile parasympathetic neurons, so we also examined expression of relevant receptors, GFRα1 and GFRα2, in injured pelvic ganglion neurons. RESULTS: Axotomy caused prolific growth of axon collaterals (sprouting) in pelvic ganglia ipsilateral to the injury. These collaterals were most prevalent in the region near the exit of the penile nerve. This region contained the majority of FluoroGold-labelled neurons. Many sprouting fibres formed close associations with sympathetic and parasympathetic pelvic neurons, including many FluoroGold neurons. However immunoreactivity for synaptic proteins could not be demonstrated in these collaterals. Preganglionic terminals showed a marked loss of synaptic proteins, suggesting a retrograde effect of the injury beyond the injured neurons. GFRα2 immunofluorescence intensity was decreased in the cytoplasm of parasympathetic neurons, but GFRα1 immunofluorescence was unaffected in these neurons. CONCLUSION: These studies show that there are profound changes within the pelvic ganglion after penile nerve injury. Sprouting of injured postganglionic axons occurs concurrently with structural or chemical changes in preganglionic terminals. New growth of postganglionic axon collaterals within the ganglion raises the possibility of the formation of aberrant synaptic connections between injured and un-injured ganglion neurons. Together these changes demonstrate a broader effect on the pelvic autonomic circuitry than simply loss of neuroeffector connections. These structural changes are accompanied by potential changes in neurotrophic factor signalling due to altered expression of receptors for members of the GDNF family. Together our results advance understanding of the responses of pelvic autonomic nerve circuits to injury and may assist in designing strategies for promoting regeneration

Pelvic Nerve Injury Causes a Rapid Decrease in Expression of Choline Acetyltransferase and Upregulation of c-Jun and ATF-3 in a Distinct Population of Sacral Preganglionic Neurons

Autonomic regulation of the urogenital organs is impaired by injuries sustained during pelvic surgery or compression of lumbosacral spinal nerves (e.g., cauda equina syndrome). To understand the impact of injury on both sympathetic and parasympathetic components of this nerve supply, we performed an experimental surgical and immunohistochemical study on adult male rats, where the structure of this complex part of the nervous system has been well defined. We performed unilateral transection of pelvic or hypogastric nerves and analyzed relevant regions of lumbar and sacral spinal cord, up to 4 weeks after injury. Expression of c-Jun, the neuronal injury marker activating transcription factor-3 (ATF-3), and choline acetyltransferase (ChAT) were examined. We found little evidence for chemical or structural changes in substantial numbers of functionally related but uninjured spinal neurons (e.g., in sacral preganglionic neurons after hypogastric nerve injury), failing to support the concept of compensatory events. The effects of injury were greatest in sacral cord, ipsilateral to pelvic nerve transection. Here, around half of all preganglionic neurons expressed c-Jun within 1 week of injury, and substantial ATF-3 expression also occurred, especially in neurons with complete loss of ChAT-immunoreactivity. There did not appear to be any death of retrogradely labeled neurons, in contrast to axotomy studies performed on other regions of spinal cord or sacral ventral root avulsion models. Each of the effects we observed occurred in only a subpopulation of preganglionic neurons at that spinal level, raising the possibility that distinct functional subgroups have different susceptibility to trauma-induced degeneration and potentially different regenerative abilities. Identification of the cellular basis of these differences may provide insights into organ-specific strategies for attenuating degeneration or promoting regeneration of these circuits after trauma

Creating change in government to address the social determinants of health: how can efforts be improved?

Background: The evidence base for the impact of social determinants of health has been strengthened considerably in the last decade. Increasingly, the public health field is using this as a foundation for arguments and actions to change government policies. The Health in All Policies (HiAP) approach, alongside recommendations from the 2010 Marmot Review into health inequalities in the UK (which we refer to as the ‘Fairness Agenda’), go beyond advocating for the redesign of individual policies, to shaping the government structures and processes that facilitate the implementation of these policies. In doing so, public health is drawing on recent trends in public policy towards ‘joined up government’, where greater integration is sought between government departments, agencies and actors outside of government. Methods: In this paper we provide a meta-synthesis of the empirical public policy research into joined up government, drawing out characteristics associated with successful joined up initiatives. We use this thematic synthesis as a basis for comparing and contrasting emerging public health interventions concerned with joined-up action across government. Results: We find that HiAP and the Fairness Agenda exhibit some of the characteristics associated with successful joined up initiatives, however they also utilise ‘change instruments’ that have been found to be ineffective. Moreover, we find that – like many joined up initiatives – there is room for improvement in the alignment between the goals of the interventions and their design. Conclusion: Drawing on public policy studies, we recommend a number of strategies to increase the efficacy of current interventions. More broadly, we argue that up-stream interventions need to be ‘fit-for-purpose’, and cannot be easily replicated from one context to the next

Bitterness suppression with zinc sulfate and na-cyclamate: a model of combined peripheral and central neural approaches to flavor modification

Purpose Zinc sulfate is known to inhibit the bitterness of the antimalarial agent quinine [R. S. J. Keast. The effect of zinc on human taste perception. J. Food Sci. 68:1871&ndash;1877 (2003)]. In the present work, we investigated whether zinc sulfate would inhibit other bitter-tasting compounds and pharmaceuticals. The utility of zinc as a general bitterness inhibitor is compromised, however, by the fact that it is also a good sweetness inhibitor [R. S. J. Keast, T. Canty, and P. A. S. Breslin. Oral zinc sulfate solutions inhibit sweet taste perception. Chem. Senses 29:513&ndash;521 (2004)] and would interfere with the taste of complex formulations. Yet, zinc sulfate does not inhibit the sweetener Na-cyclamate. Thus, we determined whether a mixture of zinc sulfate and Na-cyclamate would be a particularly effective combination for bitterness inhibition (Zn) and masking (cyclamate). Method We used human taste psychophysical procedures with chemical solutions to assess bitterness blocking. Results Zinc sulfate significantly inhibited the bitterness of quinine&ndash;HCl, Tetralone, and denatonium benzoate (DB) (p &lt; 0.05), but had no significant effect on the bitterness of sucrose octa-acetate, pseudoephedrine (PSE), and dextromethorphan. A second experiment examined the influence of zinc sulfate on bittersweet mixtures. The bitter compounds were DB and PSE, and the sweeteners were sucrose (inhibited by 25 mM zinc sulfate) and Na-cyclamate (not inhibited by zinc sulfate). The combination of zinc sulfate and Na-cyclamate most effectively inhibited DB bitterness (86%) (p &lt; 0.0016), whereas the mixture\u27s inhibition of PSE bitterness was not different from that of Na-cyclamate alone. Conclusion A combination of Na-cyclamate and zinc sulfate was most effective at inhibiting bitterness. Thus, the combined use of peripheral oral and central cognitive bitterness reduction strategies should be particularly effective for improving the flavor profile of bitter-tasting foods and pharmaceutical formulations. <br /

New citizen collectives, their democratic potential and their implications for public management

This issue-paper written by the panel-conveners introduces the panel’s topic, delineating its focus and discussing its scientific and practical relevance. It presents core concepts and ideas, aiming to provide context, direction and a common language to the panel discussions and the panelist papers. The paper discusses the rise of new citizen collectives (grass roots initiatives, community trusts, social enterprises, citizen initiatives) as new forms of civic engagement in policy fields such as energy, spatial planning, social care, community provisions and social services more generally. Under such models, citizens take the lead in dealing with common, or localized problems and public issues and are directly engaged in developing and implementing solutions and services. The emergence of citizen collectives give rise to new practical and theoretical questions concerning the meaning of these citizen collectives for local communities and government. The implications of this growing reliance of citizen collectives as vehicles for policy development and service delivery on the community sector has yet to be fully explored. In this paper, we aim to describe the rise and the forces shaping these new citizen collectives and to analyze their institutional characteristics, including to what extent they are new. Furthermore, we explore what these initiatives have to offer in terms of their democratic potential and what they mean for government and public management in particular, providing an agenda for further research into this blooming topic. The paper ends by identifying a number of issues, which if more deeply examined, will better help us to understand the functioning of citizens collectives and the challenges they face from a public management perspective. We think these issues are worthwhile for further debate during our panel and are summarized in the concluding section of this paper

The Growth of Transplanted Tumours in Mice after Chronic Inhalation of Fresh Cigarette Smoke

The subcutaneous growth of the Lewis lung tumour in C57BL mice chronically exposed to fresh cigarette smoke was increased above that in age-matched control mice. When murine sarcoma virus (Harvey) induced tumour cells were introduced to the lungs of groups of BALB/c mice, only mice chronically exposed to fresh cigarette smoke died with tumour cells in the lungs. Tumour cell growth in mice during short term cigarette smoke exposure was indistinguishable from that in controls

The concentration of oleocanthal in olive oil waste

The aim of this study was to determine the concentration of oleocanthal in olive pomace waste and compare this to its concentration in extra-virgin olive oil (EVOO). The concentration of oleocanthal in freshly pressed EVOO and its subsequent waste was analysed at early, mid and late season harvests. Oleocanthal concentrations were quantified using high-performance liquid chromatography&ndash;mass spectrometry. In oil, oleocanthal concentration was as follows: 123.24 &plusmn; 6.48 mg kg&macr;&sup1;1 in early harvest, 114.20 &plusmn; 17.42 mg kg&macr;&sup1; in mid harvest and 152.22 &plusmn; 10.54 mg kg&macr;&sup1; in late harvest. Its concentration in waste was determined to be: 128.25 &plusmn; 11.33 mg kg&macr;&sup1; in early harvest, 112.15 &plusmn; 1.51mg kg&macr;&sup1; in mid harvest and 62.35 &plusmn; 8.00 mg kg&macr;&sup1; in late harvest. Overall, olive pomace waste is a valuable source of oleocanthal.<br /

A prospective cohort study of the effects of adjuvant breast cancer chemotherapy on taste function, food liking, appetite and associated nutritional outcomes

\u27Taste\u27 changes are commonly reported during chemotherapy. It is unclear to what extent this relates to actual changes in taste function or to changes in appetite and food liking and how these changes affect dietary intake and nutritional status