Intravenous administration of adenosine triphosphate and phosphocreatine combined with fluoxetine in major depressive disorder: protocol for a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder. With systematic antidepressant treatment, 50-75% of patients have a treatment response but require 4-6 weeks to have their symptoms alleviated. Therefore, researchers anticipate the development of novel fast-acting antidepressants. Previous studies have revealed that the decrease of bio-energetic metabolism may contribute to the occurrence of depression, while our team has found adenosine triphosphate (ATP) and phosphocreatine (PCr) to be fast-acting antidepressants in the depressed-animal model. ATP and PCr have already been widely prescribed clinically as energy supplements for cells. This will be the first clinical attempt of the intravenous administration of ATP and PCr combined with orally administered fluoxetine in MDD. METHODS: This is a single-center, randomized, double-blind, placebo-controlled pilot study. A total of 42 patients will be divided randomly into three groups. Patients will receive an intravenous administration of ATP or PCr or saline twice daily combined with orally administered fluoxetine (20 mg/day) for the first 2 weeks and fluoxetine monotherapy for the following 4 weeks. Follow-up assessment will be completed at week 10. Feasibility outcomes will include percentages of patient eligibility, intention to use medication, willingness to participate, drug adherence, completion of the scheduled assessment, retention, drop-out, etc. Physical examination results, Side Effect Rating Scale, adverse events, results from blood tests, electroencephalogram, and electrocardiograph will be recorded for safety evaluation of the augmentation therapy. The trends of efficacy will be evaluated by the reduction rate of the Hamilton Depression Rating Scale, the mean change of the Clinical Global Impression Scale, and the Patients Health Questionaire-9 items. DISCUSSION: In our study, ATP and PCr will be given by intravenous infusion. Thus patients will be hospitalized for the initial 2 weeks for safety concern. Hospitalization will be an impact factor for the recruitment, participation, drop-out, efficacy, results, etc. The evaluation of our feasibility outcomes, study setting, safety of augmentation therapy and possible efficacy trends among groups, will facilitate a full-scale trial design and sample size calculation. TRIAL REGISTRATION: NCT03138681 . Registered on 3 May 2017. First patient: 4 May 2017.

Amphiphilic Functionalized Acupuncture Needle as SERS Sensor for In Situ Multiphase Detection.

Surface enhanced Raman spectroscopy (SERS) is a powerful spectroscopic technique with unique vibrational fingerprints, making it an ideal candidate for in situ multiphase detection. However, it is a great challenge to determine how to guide the SERS sensor to target molecules of interest in multiphase heterogeneous samples with minimal disturbance. Here, we present a portable ultrasensitive and highly repeatable SERS sensor for in situ multiphase detection. The sensor is composed of commercial Ag acupuncture needle and PVP-Au nanoparticles (Au NPs). The PVP on the Au NPs can adsorb and induce the Au NPs into a highly uniform array on the surface of the Ag needle because of its adhesiveness and steric nature. The Au NPs-Ag Needle system (Au-AgN) holds a huge SERS effect, which is enabled by the multiple plasmonic couplings from particle-film and interparticle. The PVP, as the amphiphilic polymer, promotes the target molecules to adsorb on surface of the Au-AgN whether in the oil phase or in the water phase. In this work, the Au-AgN sensor was directly inserted into the multiphase system with the laser in situ detection, and SERS detection at different spots of the Au-AgN sensor provided Raman signal of targets molecule in the different phase. In situ multiphase detection can minimize the disturbance of sampling and provide more accurate information. The facile fabrication and amphiphilic functionalization make Au-AgN sensor as generalized SERS detection platform for on-site testing of aqueous samples, organic samples, even the multiphase heterogeneous samples.

Functionalized Acupuncture Needle as Surface-Enhanced Resonance Raman Spectroscopy Sensor for Rapid and Sensitive Detection of Dopamine in Serum and Cerebrospinal Fluid.

It is a challenge to develop a robust sensor for simple, rapid operation and sensitive detection of neurotransmitters in complex specimens. Herein, ferric citrate functionalized gold nanoparticles (CA-FeIII /Au NPs) are utilized to develop a facile sensor based on surface-enhanced resonance Raman spectroscopy (SERRS) for sensitive detection of dopamine (DA). The sensor is prepared by decorating the acupuncture needle with Au NPs, which enables sufficient surface-enhanced Raman spectroscopy enhancement. The CA-FeIII structure is highly sensitive and selective for DA due to the formation of the CA-FeIII -DA resonant structure; this indicates the advantages of capturing, carrying, and separating DA molecules from complicated samples in a simple operation. Furthermore, the practical application of the fabricated sensor is validated by the detection of DA in pretreated serum and cerebrospinal fluid of acupuncture-treated mice with detection limits of 0.1 and 2.5 nm DA, respectively. The developed active acupuncture needle sensor has potential benefits for sensitive detection and qualitative identification of DA molecules from biological samples.