Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3–4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs.
Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance. Specifically, it discusses: (1) the data on the association between antidepressant drug efficacy and genetically defined characteristics of key proteins in the 5-HT signaling (TPH2, MAOA, SERT and 5-HT1A receptor), (2) the effect of dimerization of 5-HT7 and 5-HT1A receptors on the internalization and functioning of 5-HT1A presynaptic receptors, (3) the role of Tph2 deficiency in the resistance to SSRIs treatment. We shift the emphasis from individual proteins to their interactions in explaining antidepressant action of SSRI.
Expert opinion: These interactions should be considered when developing more effective antidepressant drugs as well as for predicting and improving the efficacy of antidepressant therapies. 相似文献
Protection against diseases caused by the avian viruses, Marek's disease, Infectious laryngotracheitis, chicken anemia and turkey meningoencephalitis is achieved by live vaccines. The application quality is important to assure proper uptake in commercial flocks. We describe a novel evaluation method for the vaccination process by sequential monitoring the vaccine viruses in feathers. Feather collection is easy, non-invasive and non-lethal for the birds, therefore advantageous for monitoring purposes. To demonstrate the vaccine virus presence, an innovative assay of nested real-time amplification was approached because vaccine viruses presence in vivo is less abundant comparing to virulent wild-type isolates.The Marek's disease virus vaccine virus, Rispens/CVI988, in feathers of commercial flock was detected from 4 to 7 days and for at least 3 months post-vaccination, until the survey stopped. As the drinking water route was newly adopted for Infectious laryngotracheitis vaccination, one or two vaccine doses/bird were administered. The virus uptake was detected in feathers between 2 and 20 days-post-vaccination. With a doubled vaccine dose the positivity bird rate was higher. For the first time the chicken anemia vaccine virus presence in chicken feathers was demonstrated between 14 and 35 days-post-vaccination. No previous studies were available, thus in parallel to feathers the vaccine virus was demonstrated in the livers and spleens. The turkey meningoencephalitis vaccine virus uptake in turkey feather-pulps is even more innovative because this is the first turkey virus amplified from feather-pulps. The vaccine virus presence resemble the kinetics of the other 3 viruses, 3–21 days-post-vaccination. Detecting the specific antibodies following vaccination possessed a lower sensitivity than vaccine virus demonstration in feathers. In summary, the presented assay can be adopted for the quality evaluation of the vaccination process in poultry. 相似文献
BackgroundAchilles tendon rupture (ATR) is one of the most frequently encountered injuries in Sports Medicine. ATR can be managed surgically or conservatively followed by early functional rehabilitation or cast immobilization. The aim of the present systematic review and meta-analysis was to provide an update about the role of early weightbearing (WB) versus late WB on the clinical outcomes of adults with acute ATR.MethodsWe performed a systematic literature search in Web of Science, Ovid, Medline/PubMed, and CENTRAL. We included randomized controlled trials (RCTs) that compared early WB, defined as weight-bearing within 4 weeks of treatment, to late WB for individuals with acute (<14 days) ATR. We sought to evaluate the following outcomes: re-rupture rate, Achilles Tendon Rupture Score (ATRS), return to pre-injury sport activity, time to return to work, and adverse event rate. The standardized mean difference (SMD) was used to represent continuous outcomes while the risk ratio (RR) was used to represent dichotomous outcomes.ResultsA total of 9 RCTs that enrolled 1046 participants were deemed eligible. There was no significant difference between early WB and late WB in terms of re-rupture rate (RR=0.75, 95% CI 0.49 to 1.16), ATRS (SMD=0.06, 95% CI –0.03 to 0.16), return to pre-injury sport activity (RR=1.05, 95% CI 0.86 to 1.28), time to return to work (SMD=0.03, 95% CI –0.20 to 0.26), or adverse event rate (RR=1.87, 95% CI 0.53 to 6.63).ConclusionThis meta-analysis shows no difference in the functional outcomes and patient-reported outcomes between early functional rehabilitation and cast immobilization for conservatively treat individuals with acute ATR. 相似文献
BackgroundPaediatric age-adjusted shock index (SIPA) has emerged as a predictor of morbidity and mortality in trauma. Poor sensitivity and low generalisability demonstrated in previous studies have limited its use. We evaluate the use of SIPA in the general Australian paediatric trauma population and the combination of SIPA with GCS.MethodsAll patients from January 2015 to August 2020 at a major Australian paediatric trauma centre were reviewed. Pre-arrival SIPA (pSIPA) and arrival SIPA (aSIPA) were calculated. If SIPA was elevated or the Glasgow Coma Scale ≤ 13, SIPA with mental state (SIPAms) was marked positive for pre-arrival (pSIPAms) and arrival (aSIPAms) respectively.Results/DiscussionData from 480 patients were analysed. pSIPA and aSIPA poorly predicted outcomes of morbidity. Only aSIPA predicted mortality. However, both pre-arrival and arrival SIPAms variables predict mortality, major trauma (ISS≥12), hospital LOS, need for ICU admission, and major surgery. Furthermore, median ISS and lactate were significantly higher in positive pSIPA, aSIPA, pSIPAms, and aSIPAms groups than negative. aSIPAms has a sensitivity of 76% and specificity of 70% for major trauma.ConclusionBroad inclusion criteria reduce SIPA's ability to predict morbidity. Combining it with GCS improves this and is most valuable when calculated at arrival. In addition, the score is more reliable for major trauma (ISS≥12). Future studies should evaluate the use of SIPAms in activation criteria. 相似文献