ABSTRACT
Many studies implicate altered cyclic nucleotide signaling in the pathophysiology of major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). As such, we explored how phosphodiesterases 2A (PDE2A) and 10A (PDE10A)-enzymes that break down cyclic nucleotides-may be altered in brains of these patients. Using autoradiographic in situ hybridization on postmortem brain tissue from the Stanley Foundation Neuropathology Consortium, we measured expression of PDE2 and PDE10 mRNA in multiple brain regions implicated in psychiatric pathophysiology, including cingulate cortex, orbital frontal cortex (OFC), superior temporal gyrus, hippocampus, parahippocampal cortex, amygdala, and the striatum. We also assessed how PDE2A and PDE10A expression changes in these brain regions across development using the Allen Institute for Brain Science Brainspan database. Compared to controls, patients with SCZ, MDD and BPD all showed reduced PDE2A mRNA in the amygdala. In contrast, PDE2A expression changes in frontal cortical regions were only significant in patients with SCZ, while those in caudal entorhinal cortex, hippocampus, and the striatum were most pronounced in patients with BPD. PDE10A expression was only detected in striatum and did not differ by disease group; however, all groups showed significantly less PDE10A mRNA expression in ventral versus dorsal striatum. Across development, PDE2A mRNA increased in these brain regions; whereas, PDE10A mRNA expression decreased in all regions except striatum. Thus, PDE2A mRNA expression changes in both a disorder- and brain region-specific manner, potentially implicating PDE2A as a novel diagnostic and/or patient-selection biomarker or therapeutic target.
Subject(s)
Aging/metabolism , Bipolar Disorder/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 2/metabolism , Depressive Disorder, Major/metabolism , Phosphoric Diester Hydrolases/metabolism , Schizophrenia/metabolism , Adult , Animals , Biomarkers/metabolism , Brain/metabolism , Brain/pathology , Case-Control Studies , Female , Humans , Male , Mice , Middle Aged , RNA, Messenger/metabolismABSTRACT
A cross-sectional study was conducted aimed at determining the frequency and the risk factors for bacteremia caused by extended-spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae in patients hospitalized in a public hospital in Lima. The study included patients over 14 years of age, with positive blood cultures during their hospitalization in Hospital Nacional Cayetano Heredia in 2016. Patients were classified according to the isolated bacterium (ESBL-producing or not). Bacteremia was caused by ESBL-producing Enterobacteriacea in 50.6% of the cases; 55.8% and 32.6% by E. Coli and K. pneumoniae, respectively. No differences were found regarding co-morbidity, or prior antibiotic use (62.8% of bacteremia due to ESBLproducing strains and 57% in the non-producing strains [p=0.595]). Half of the bacteremia cases due to Enterobacteriaceae in hospitalized patients are produced by ESBL-producing Enterobacteriaceae and, of these, 40% are acquired in the community.
Con el objetivo de determinar la frecuencia y factores de riesgo para bacteriemia por enterobacterias productoras de betalactamasa de espectro extendido (BLEE) en pacientes internados en un hospital público de Lima se realizó un estudio transversal. Fueron incluidos pacientes mayores de 14 años, con hemocultivos positivos durante su hospitalización en el Hospital Nacional Cayetano Heredia el 2016. Se clasificó a los pacientes según la bacteria aislada (productora o no de BLEE). El 50,6 % de las bacteriemias fueron causadas por enterobacterias productoras de BLEE, 55,8 % y 32,6 % por E. Coli y K. pneumoniae, respectivamente. No hallándose diferencias con relación a comorbilidades, ni uso previo de antibióticos (62,8 % de las bacteriemias por cepas productoras de BLEE y en 57 % en las no productoras (p=0,595)). La mitad de las bacteriemias por enterobacterias en pacientes hospitalizados son producidas por enterobacterias productoras de BLEE, y de estas, el 40 % son adquiridas en la comunidad.
Subject(s)
Bacteremia/epidemiology , Bacteremia/microbiology , Cross Infection/epidemiology , Cross Infection/microbiology , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/enzymology , beta-Lactamases/biosynthesis , Cross-Sectional Studies , Hospitals, Public , Humans , Peru , Risk Factors , Urban HealthABSTRACT
RESUMEN Con el objetivo de determinar la frecuencia y factores de riesgo para bacteriemia por enterobacterias productoras de betalactamasa de espectro extendido (BLEE) en pacientes internados en un hospital público de Lima se realizó un estudio transversal. Fueron incluidos pacientes mayores de 14 años, con hemocultivos positivos durante su hospitalización en el Hospital Nacional Cayetano Heredia el 2016. Se clasificó a los pacientes según la bacteria aislada (productora o no de BLEE). El 50,6 % de las bacteriemias fueron causadas por enterobacterias productoras de BLEE, 55,8 % y 32,6 % por E. Coli y K. pneumoniae, respectivamente. No hallándose diferencias con relación a comorbilidades, ni uso previo de antibióticos (62,8 % de las bacteriemias por cepas productoras de BLEE y en 57 % en las no productoras (p=0,595)). La mitad de las bacteriemias por enterobacterias en pacientes hospitalizados son producidas por enterobacterias productoras de BLEE, y de estas, el 40 % son adquiridas en la comunidad.
ABSTRACT A cross-sectional study was conducted aimed at determining the frequency and the risk factors for bacteremia caused by extended-spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae in patients hospitalized in a public hospital in Lima. The study included patients over 14 years of age, with positive blood cultures during their hospitalization in Hospital Nacional Cayetano Heredia in 2016. Patients were classified according to the isolated bacterium (ESBL-producing or not). Bacteremia was caused by ESBL-producing Enterobacteriacea in 50.6% of the cases; 55.8% and 32.6% by E. Coli and K. pneumoniae, respectively. No differences were found regarding co-morbidity, or prior antibiotic use (62.8% of bacteremia due to ESBLproducing strains and 57% in the non-producing strains [p=0.595]). Half of the bacteremia cases due to Enterobacteriaceae in hospitalized patients are produced by ESBL-producing Enterobacteriaceae and, of these, 40% are acquired in the community.
