Characterization of electroencephalographic and biochemical responses at 5‐HT promoting drug‐induced onset of serotonin syndrome in rats

Many psychotropic substances used either for medications or illicit recreational purposes are able to produce an increase in extracellular serotonin (5HT) in the CNS. 5HT is well known to improve mood; however, only when the levels of its release are in an appropriate range. Excessive 5HT is harmful, and will generally result in serotonin syndrome. To date, clinical diagnosis of serotonin syndrome relies exclusively on observation of symptoms because of a lack of available laboratory tests. The goal of this study was to characterize the onset of the syndrome using laboratory settings to determine excessive 5HT‐evoked neurological abnormalities. Experiments were carried out in rats with the syndrome being elicited by three groups of 5HT‐promoting drugs: (i) (±)‐3,4‐methylenedioxymethamphetamine (MDMA); (ii) a combination of the monoamine oxidase inhibitor clorgyline with the 5HT precursor 5‐hydroxytryptophan; (iii) clorgyline combined with the serotonin‐selective reuptake inhibitor paroxetine. The onset of the syndrome was characterized by electroencephalography (EEG), tremor, and brain/plasma 5HT tests. We found that a mild syndrome was associated with reduced EEG amplitudes while a severe syndrome strongly with seizure‐like EEG activity and increased tremor activity. The occurrence of the syndrome was confirmed with microdialysis, showing excessive 5HT efflux in brain dialysate and the increased concentration of unbound 5HT in the plasma. Our findings suggest that the syndrome onset can be revealed with EEG recording, measurements of tremor activity and changes of unbound 5HT concentration in the plasma.     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

Lessons learned from placebo groups in antidepressant trials

This comprehensive review provides an overview about placebo and nocebo phenomena in antidepressant trials. Improvements in the placebo groups may partly be explained through methodological issues such as natural course of depression and regression to the mean, but also fundamentally reflect investigators' and participants' expectations. A meta-analysis by our group of 96 randomized placebo-controlled trials showed large placebo responses to antidepressant medication. Moderator analyses revealed substantially larger placebo responses in observer ratings compared with self-report. Effect sizes in observer ratings showed strong increase with publication year while this effect was not found for patients' self-ratings. This reflects the strong influence of investigators' expectations. The analysis of 'nocebo effects', e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors. While the placebo response seems to be similar for women and men, gender differences were found for nocebo rates. In the conclusion, we discuss potential implications for clinical trial designs and argue for interventions aimed at optimizing positive expectations of treatment benefit while minimizing the impact of adverse effects.     

自动设别技术在医院药品供应和管理体系中的应用

?????? 运用医院电子化药品物流平台,贯穿整个医院药品物流供应过程,并结合运用条形码扫描自动识别技术来判别调配药品以及数量的准确性,同时客观记录人员绩效管理数据。盘点误差由使用前的0.24%,降至零;2011年度验收拒收药品共74次;专业技术人员配备由7名降至5名。整个电子化药品物流平台贯穿医院药品物流始终,能确保入院药品信息准确,杜绝调剂差错,有效提升人员绩效管理,真正发挥药师应有的专业特长,更好地为患者服务。

     

High frequency of leaf swallowing and its relationship to intestinal parasite expulsion in "village" chimpanzees at Bulindi, Uganda

Self-medication by great apes to control intestinal parasite infections has been documented at sites across Africa. Chimpanzees (Pan troglodytes) swallow the leaves of certain plant species whole, without chewing. Previous studies demonstrated a relationship between chimpanzee leaf swallowing and expulsion of nematode worms (Oesophagostomum sp.) and tapeworms (Bertiella sp.) in dung. We investigated the relationship between leaf swallowing and parasite expulsion in chimpanzees inhabiting a fragmented forest-farm mosaic at Bulindi, Uganda. During 13 months whole undigested leaves occurred in chimpanzee dung at a considerably higher frequency (10.4% of dungs) than at other sites (0.4-4.0%). Leaf swallowing occurred year-round and showed no pronounced seasonality. Chimpanzees egested adults of multiple species of Oesophagostomum (including O. stephanostomum) and proglottids of two tapeworms-Bertiella sp. and probably Raillietina sp. The latter may not be a true infection, but the byproduct of predation on domestic fowl. Compared to previous studies, the co-occurrence of whole leaves and parasites in chimpanzee dung was low. Whereas the presence of leaves in dung increased the probability of adult nematode expulsion, no association between leaf swallowing and the shedding of tapeworm proglottids was apparent. Anthropogenic habitat changes have been linked to alterations in host-parasite interactions. At Bulindi, deforestation for agriculture has increased contact between apes and people. Elevated levels of leaf swallowing could indicate these chimpanzees are especially vulnerable to parasite infections, possibly due to environmental changes and/or increased stress levels arising from a high frequency of contact with humans. Frequent self-medication by chimpanzees in a high-risk environment could be a generalized adaptation to multiple parasite infections that respond differently to the behavior. Future parasitological surveys of apes and humans at Bulindi are needed for chimpanzee health monitoring and management, and to investigate the potential for disease transmission among apes, people, and domestic animals.     

The tail suspension test

The tail-suspension test is a mouse behavioral test useful in the screening of potential antidepressant drugs, and assessing of other manipulations that are expected to affect depression related behaviors. Mice are suspended by their tails with tape, in such a position that it cannot escape or hold on to nearby surfaces. During this test, typically six minutes in duration, the resulting escape oriented behaviors are quantified. The tail-suspension test is a valuable tool in drug discovery for high-throughput screening of prospective antidepressant compounds. Here, we describe the details required for implementation of this test with additional emphasis on potential problems that may occur and how to avoid them. We also offer a solution to the tail climbing behavior, a common problem that renders this test useless in some mouse strains, such as the widely used C57BL/6. Specifically, we prevent tail climbing behaviors by passing mouse tails through a small plastic cylinder prior to suspension. Finally, we detail how to manually score the behaviors that are manifested in this test.     

Evidence for collective medication in ants

Social organisms are exposed to many pathogens, and have evolved various defence mechanisms to limit the cost of parasitism. Here we report the first evidence that ants use plant compounds as a collective mean of defence against microorganisms. The wood ants Formica paralugubris often incorporate large quantities of solidified conifer resin into their nests. By creating resin‐free and resin‐rich experimental nests, we demonstrate that this resin inhibits the growth of microorganisms in a context mimicking natural conditions. Such a collective medication probably confers major ecological advantages, and may be an unrecognized yet common feature of large, complex and successful societies.     

Dopaminergic modulation of multi-muscle synergies in postural tasks performed by patients with Parkinson’s disease

BackgroundPostural instability is one of most disabling motor symptoms in Parkinson’s disease. Indices of multi-muscle synergies are new measurements of postural stability.ObjectivesWe explored the effects of dopamine-replacement drugs on multi-muscle synergies stabilizing center of pressure coordinate and their adjustments prior to a self-triggered perturbation in patients with Parkinson’s disease. We hypothesized that both synergy indices and synergy adjustments would be improved on dopaminergic drugs.MethodsPatients at Hoehn-Yahr stages II and III performed whole-body tasks both off- and on-drugs while standing. Muscle modes were identified as factors in the muscle activation space. Synergy indices stabilizing center of pressure in the anterior-posterior direction were quantified in the muscle mode space during a load-release task.ResultsDopamine-replacement drugs led to more consistent organization of muscles in stable groups (muscle modes). On-drugs patients showed larger indices of synergies and anticipatory synergy adjustments. In contrast, no medication effects were seen on anticipatory postural adjustments or other performance indices.ConclusionsDopamine-replacement drugs lead to significant changes in characteristics of multi-muscle synergies in Parkinson’s disease. Studies of synergies may provide a biomarker sensitive to problems with postural stability and agility and to efficacy of dopamine-replacement therapy.     

Eveningness has the increased odds for spinal diseases but the decreased odds for articular diseases with prospective hospital treatments

Eveningness has been associated with multiple health risks, including articular and spinal diseases. Here, we analyzed if higher risks for articular and spinal diseases among Evening-types are also seen as increased treatments severe enough to require hospitalization. Our sample consists of 5696 Finnish adults from the general population with information on treatments during 1987–2010 based on the national hospital discharge register (HILMO). Their chronotype was assessed as part of the national health examination study (FINRISK) in 2007. From 2007 to 2010, the risk for dorsopathies was significantly higher (OR = 1.8, p < 0.05) but that for arthropathies was significantly lower (OR = 0.5, p < 0.05) for Evening-types than for Morning-types, after controlling for a range of potential confounding factors. Based on the clinical diagnoses assessed during hospital treatment, our study demonstrates that the eveningness associates significantly with the increased odds for dorsopathies.