15 research outputs found
The Two Enantiomers of Citalopram Bind to the Human Serotonin Transporter in Reversed Orientations
The Danish Myelodysplastic Syndromes Database:Patient Characteristics and Validity of Data Records
BACKGROUND: The Danish Myelodysplastic Syndromes Database (DMDSD) comprises nearly all patients diagnosed with myelodysplastic syndromes (MDS) in Denmark since 2010. The DMDSD has not yet been used for epidemiological research and the quality of registered variables remains to be investigated. OBJECTIVE: To describe characteristics of the patients registered in the DMDSD and to calculate predictive values and the proportion of missing values of registered data records. METHODS: We performed a nationwide cross-sectional validation study of recorded disease and treatment data on MDS patients during 2010–2019. Patient characteristics and the proportion of missing values were tabulated. A random sample of 12% was drawn to calculate predictive values with 95% confidence intervals (CIs) of 48 variables using information from medical records as a reference standard. RESULTS: Overall, 2284 patients were identified (median age: 76 years, men 62%). Of these, 10% had therapy-related MDS, and 6% had an antecedent hematological disease. Hemoglobin level was less than 6.2 mmol/L for 59% of patients. Within the first two years of treatment, 59% received transfusions, 35% received erythropoiesis-stimulating agents, and 15% were treated with a hypomethylating agent. For the majority of variables (around 80%), there were no missing data. A total of 260 medical records were available for validation. The positive predictive value of the MDS diagnosis was 92% (95% CI: 88–95). Predictive values ranged from 64% to 100% and exceeded 90% for 36 out of 48 variables. Stratification by year of diagnosis suggested that the positive predictive value of the MDS diagnosis improved from 88% before 2015 to 95% after. CONCLUSION: In this study, there was a high accuracy of recorded data and a low proportion of missing data. Thus, the DMDSD serves as a valuable data source for future epidemiological studies on MDS
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Binding of Serotonin to the Human Serotonin Transporter.:Molecular Modeling and Experimental Validation.
The Two Enantiomers of Citalopram Bind to the Human Serotonin Transporter in Reversed Orientations
R-CHOP(-like) treatment of diffuse large B-cell lymphoma significantly reduces CT-assessed vertebral bone density:a single center study of 111 patients
Binding of the Amphetamine-like 1-Phenyl-piperazine to Monoamine Transporters
The human serotonin transporter (hSERT), the human dopamine
transporter
(hDAT), and the human norepinephrine transporter (hNET) facilitate
the active uptake of the neurotransmitters serotonin, dopamine, and
norepinephrine from the synaptic cleft. Drugs of abuse such as MDMA
(streetname “ecstasy”) and certain 1-phenyl-piperazine
(PP) analogs such as 1-(3-chlorophenyl)-piperazine (mCPP) elicit their
stimulatory effect by elevating the synaptic concentration of serotonin
by blocking or reversing the normal transport activity of hSERT. Recent
data suggest that certain analogs of PP may be able to counteract
the addictive effect of cocaine. Little is still known about the precise
mechanism by which MDMA and PP analogs function at hSERT, hDAT, and
hNET and even less is known about the specific protein–ligand
interactions. In this study, we provide a comprehensive biochemical
examination of a repertoire of PP analogs in hSERT, hDAT, and hNET.
Combined with induced fit docking models and molecular dynamics simulations
of PP and 1-(3-hydroxyphenyl)-piperazine (3-OH-PP) bound to hSERT
and hDAT, we present detailed molecular insight into the promiscuous
binding of PP analogs in the monoamine transporters. We find that
PP analogs inhibit uptake as well as induce release in all three monoamine
transporters. We also find that the selectivity of the PP analogs
can be adjusted by carefully selecting substituents on the PP skeleton