Evaluating podiatry services: Testing a treatment specific measure of health status

This study reports on the preliminary testing of a new measure designed for use alongside EQ-5D in evaluating outcomes in podiatry: the Podiatry Health Questionnaire (PHQ). Individuals aged 18 years or more, receiving podiatry services in clinic or domicilliary locations across four NHS Trusts in Yorkshire and Humberside UK took part in a questionnaire survey. Respondents reported high levels of problems on all six PHQ dimensions. Correlations suggested that the PHQ and EQ-5D were measuring distinct constructs. The levels on each dimension were well defined in terms of self-rated morbidity on the PHQ visual analogue scale (PHQ_vas) and the EQ-5D_vas, although PHQ_vas appeared to be slightly more sensitive to changes in health on the dimensions. There was a strong relationship between clinicians' Podiatry Clinical Score rating and reported symptoms for four out of six PHQ dimensions and PHQ_vas. The PHQ was able to distinguish respondents in terms of their self-reported morbidity in EQ-5D and in terms of their morbidity as assessed by clinicians. It is suggested that the respondent completed PHQ appears to be a useful new measure for assessing foot-related health. However, further investigation of the psychometric properties of the measure is required.     

Synaptic potentials and effects of amino acid antagonists in the auditory cortex

Neurons of in vitro guinea pig and rat auditory cortex receive a complex synaptic pattern of afferent information. As many as four synaptic responses to a single-stimulus pulse to the gray or white matter can occur; an early-EPSP followed, sequentially, by an early-IPSP, late-EPSP, and late-IPSP. Paired pulse stimulation and pharmacological studies show that the early-IPSP can modify information transmission that occurs by way of the early-EPSP. Each of these four synaptic responses differed in estimated reversal potential, and each was differentially sensitive to antagonism by pharmacological agents. DNQX (6,7-dinitroquinoxaline-2,3-dione), a quisqualate/kainate receptor antagonist, blocked the early-EPSP, and the late-EPSP was blocked by the NMDA receptor antagonist APV (D-2-amino-5-phosphonovalerate). The early-IPSP was blocked by the GABA-a receptor antagonist bicuculline, and the late-IPSP by the GABA-b receptor antagonists 2-OH saclofen or phaclofen. Presentation of stimulus trains, even at relatively low intensities, could produce a long-lasting APV-sensitive membrane depolarization. Also discussed is the possible role of these synaptic potentials in auditory cortical function and plasticity.     

S-100 beta and insulin-like growth factor-II differentially regulate growth of developing serotonin and dopamine neurons in vitro.

To study the phenotypic specificity of S-100 beta and insulin-like growth factor II (IGF-II) for developing monoamine neurons, serotonin (5-HT) neurons from the embryonic day 14 (E14) rostral raphe or dopamine (TH) neurons from the substantia nigra/ventral tegmental area were cultured for 3 days in vitro (3 DIV) in the presence of these factors. Neuronotrophic effects were analyzed by computer-assisted morphometry of 5-HT and TH-immunoreactive neurons. S-100 beta and IGF-II differentially regulated the growth of 5-HT and TH neurons but did not affect their survival. S-100 beta significantly increased several parameters of neurite outgrowth by 5-HT neurons but inhibited the spatial extent (field area) of TH neurites. IGF-II promoted growth of cell bodies of both phenotype, but only stimulated neurite outgrowth by TH neurons. S-100 beta and IGF-II differentially affected the number of GFAP immunoreactive cells from raphe and substantia nigra, but these effects did not correlate with the specificity of neuronotrophic effects. S-100 beta and IGF-II immunoreactivities were expressed in glial cultures derived from the same brain regions, raising the possibility that these factors have autocrine effects on glia as well as paracrine actions on neurons. The results of this study suggest that specificity of neurotrophic factors for particular embryonic neurons may be correlated with their neurotransmitter phenotype.     

Acute selective serotonin reuptake inhibitors increase conditioned fear expression: blockade with a 5-HT(2C) receptor antagonist.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) effectively treat various anxiety disorders, although symptoms of anxiety are often exacerbated during early stages of treatment. We previously reported that acute treatment with the SSRI citalopram enhances the acquisition of auditory fear conditioning, which is consistent with the initial anxiogenic effects reported clinically. Here, we extend our findings by assessing the effects of acute SSRI treatment on the expression of previously acquired conditioned fear. METHODS: Rats underwent fear conditioning drug-free. Tone-evoked fear responses were tested after drug treatment the following day. This protocol more closely resembles the clinical setting than pre-conditioning treatment, because it evaluates effects of treatment on a pre-existing fear rather than on the formation of a new fear memory. RESULTS: A single pre-testing injection of the SSRIs citalopram or fluoxetine significantly increased fear expression. There was no effect of the antidepressant tianeptine or the norepinephrine reuptake inhibitor tomoxetine, indicating that this effect is specific to SSRIs. The SSRI-induced enhancement in fear expression was not blocked by tropisetron, a 5-HT(3) receptor antagonist, but was blocked by SB 242084, a specific 5-HT(2C) receptor antagonist. CONCLUSIONS: Enhanced activation of 5-HT(2C) receptors might be a mechanism for the anxiogenic effects of SSRIs observed initially during treatment.     

An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity

Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of dengue viruses (DENVs). This disease, which is prevalent in over a hundred tropical and sub-tropical countries of the world, represents a significant global public health problem. A tetravalent dengue vaccine capable of protecting against all four DENV serotypes has been elusive so far. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we have utilized a discrete carboxy-terminal region of the major DENV envelope (E) protein, known as domain III (EDIII), which mediates virus entry into target cells and contains multiple serotype-specific neutralizing epitopes, to create a chimeric tetravalent antigen. This antigen derived by in-frame fusion of the EDIII-encoding sequences of the four DENV serotypes was expressed using a replication-defective recombinant human adenovirus type 5 (rAdV5) vaccine vector. This rAdV5 vector induced cell-mediated immune responses and virus-neutralizing antibodies specific to each of the four DENVs in mice. Interestingly, anti-AdV5 antibodies did not suppress the induction of DENV-specific neutralizing antibodies. We observed that anti-AdV5 antibodies in the sera of immunized mice could promote uptake of a rAdV5-derived reporter vector into U937 cells, suggesting that pre-existing immunity to AdV5 may in fact facilitate the uptake of rAdV5 vectored vaccines into antigen presenting cells. This work presents an alternative approach to developing a single component tetravalent vaccine that bypasses the complexities inherent in the currently adopted four-in-one physical mixture approach.     

血清1,5-脱水葡糖醇的测定及在糖尿病诊断中的应用

目的:应用血清1,5-脱水葡糖醇(1,5AG)的酶动力学法,探讨其在糖尿病诊断中的应用价值。方法:应用全自动生化分析仪,采用全酶法测定健康人和糖尿病患者血清1,5AG的含量。结果:该法测定血清1,5AG精密度好,高、低值混合血清的CV分别为1.47％和1.70％;回收率分别为98.28％、101.32％和97.64％、103.36％,平均回收率为100.15％;在1,5-AG浓度为360μmol/L内呈良好的线性;60例糖尿患者血清1,5AG(5.38-59.54μmol/L)明显低于健康人(60.89～269.79μmol/L),P<0.01。结论:该方法重复性好,准确度高,工作试剂在2 d内稳定,适合常规实验室开展;血清1,5AG测定有助于糖尿病的诊断和治疗过程的监控。     

小肠吸收胆固醇的分子生物学研究进展

胆固醇通过分布于十二指肠和近段空肠黏膜上皮细胞刷状缘膜的Niemann—Pick C1样蛋白1摄取，ATP结合盒G5、G8抑制小肠对胆固醇的摄取过程。进入上皮细胞的胆固醇大多数被乙酰辅酶A，胆固醇转乙酰基酶2酯化，随后通过组装形成乳糜微粒，经淋巴管进入血循环；另一部分胆固醇则以未酯化形式直接进入血循环形成高密度脂蛋白颗粒。这些过程受核受体——肝脏X受体的调控。年龄、性别、黏膜屏障和小肠传输速度也影响胆固醇的吸收。     

Airway hyper-responsiveness to adenosine 5''-monophosphate in preschool-age children with asthma

Airway hyper-responsiveness (AHR) to adenosine 5'-monophosphate (AMP) is closely associated with airway inflammation; however, not all asthmatic patients are responsive to it. This study was planned to investigate the predictive factors of AHR to AMP in asthmatic children aged between 3 and 6 yr. We performed a retrospective analysis of data from 63 asthmatic preschool-age children who were challenged by AMP in our department. All children were characterized by skin-prick tests, serum immunoglobulin E (IgE) levels, peripheral blood eosinophil percentage and bronchial challenge with methacholine (MCH) and AMP. Potential determinants for AHR to AMP were assessed within the group. AHR to AMP was found in 46% of preschool-age children with asthma, while that of MCH was 93.7%. All children responsive to AMP were also responsive to MCH. The geometric mean provocative concentration of MCH and AMP causing a 15% fall in transcutaneous oxygen tension (PC(15)PtcO(2)MCH and AMP) were 0.55 mg/ml (0.004-9.19) and 10.53 mg/ml (0.59-342.89), respectively. AMP-responsive children did not differ from non-responsive ones with respect to demographic factors, geometric mean PC(15)PtcO(2)MCH and atopic status. The median serum IgE level was significantly higher in AMP-responsive group than the non-responsive ones (p = 0.011). The peripheral blood eosinophilia was more frequent among responsive children (p = 0.019), and it was found as the only predictive factor for AMP responsiveness in preschool-age children with asthma in logistic regression model (odds ratio: 5.14; 95% CI: 1.23-21.47; p = 0.025). AMP responsiveness may be predicted by peripheral blood eosinophilia but not with atopy markers in young children with asthma.