ABSTRACT
Healthcare-associated infections (HAIs) represent a global challenge and an even more staggering concern when related to microorganisms capable of resisting and surviving for long periods in the environment, such as Acinetobacter spp. Strategies that allow a reduction of pathogens from hospital environments represent an additional barrier in infection control protocols, minimizing transmission to hospitalized patients. Considering the antimicrobial properties of copper, here, the bacterial load and the presence of Acinetobacter spp. were monitored on high handling surfaces covered by 99.9% copper films on intensive and non-intensive care unit bedrooms in a tertiary care hospital. Firstly, copper-coated films were able to inhibit the adhesion and biofilm formation of A. baumannii strains in in vitro assays. On the other hand, Acinetobacter spp. were isolated from both copper-coated and uncoated surfaces in the hospital, although the majority was detected on surfaces without copper. All carbapenem-resistant A. baumannii isolates identified harbored the blaoxa-23 gene, while the A. nosocomialis isolates were susceptible to most antimicrobials tested. All isolates were susceptible to polymyxin B. Regarding the total aerobic bacteria, surfaces with copper-coated films presented lower total loads than those detected for controls. Copper coating films may be a workable strategy to mitigate HAIs, given their potential in reducing bacterial loads in nosocomial environments, including threatening pathogens like A. baumannii.
ABSTRACT
Gestational methylazoxymethanol acetate (MAM) treatment produces offspring with adult phenotype relevant to schizophrenia, including positive- and negative-like symptoms, cognitive deficits, dopaminergic dysfunction, structural and functional abnormalities. Here we show that adult rats prenatally treated with MAM at gestational day 17 display significant increase in dopamine D3 receptor (D3) mRNA expression in prefrontal cortex (PFC), hippocampus and nucleus accumbens, accompanied by increased expression of dopamine D2 receptor (D2) mRNA exclusively in the PFC. Furthermore, a significant change in the blood perfusion at the level of the circle of Willis and hippocampus, paralleled by the enlargement of lateral ventricles, was also detected by magnetic resonance imaging (MRI) techniques. Peripubertal treatment with the non-euphoric phytocannabinoid cannabidiol (30 mg/kg) from postnatal day (PND) 19 to PND 39 was able to reverse in MAM exposed rats: i) the up-regulation of the dopamine D3 receptor mRNA (only partially prevented by haloperidol 0.6 mg/kg/day); and ii) the regional blood flow changes in MAM exposed rats. Molecular modelling predicted that cannabidiol could bind preferentially to dopamine D3 receptor, where it may act as a partial agonist according to conformation of ionic-lock, which is highly conserved in GPCRs. In summary, our results demonstrate that the mRNA expression of both dopamine D2 and D3 receptors is altered in the MAM model; however only the transcript levels of D3 are affected by cannabidiol treatment, likely suggesting that this gene might not only contribute to the schizophrenia symptoms but also represent an unexplored target for the antipsychotic activity of cannabidiol.
Subject(s)
Brain/drug effects , Cannabidiol/pharmacology , Receptors, Dopamine D3/genetics , Schizophrenia/drug therapy , Animals , Antipsychotic Agents/pharmacology , Brain/diagnostic imaging , Cannabidiol/chemistry , Cerebrovascular Circulation , Disease Models, Animal , Female , Gene Expression Regulation , Haloperidol/chemistry , Haloperidol/pharmacology , Magnetic Resonance Imaging , Male , Methylazoxymethanol Acetate/toxicity , Models, Molecular , Molecular Dynamics Simulation , Pregnancy , Prenatal Exposure Delayed Effects , Puberty , Rats, Sprague-Dawley , Receptors, Dopamine D2/chemistry , Receptors, Dopamine D2/genetics , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3/chemistry , Receptors, Dopamine D3/metabolism , Schizophrenia/chemically induced , Schizophrenia/diagnostic imaging , Schizophrenia/geneticsABSTRACT
The dopamine D3 receptor (D3R), in the nucleus accumbens (NAc), plays an important role in alcohol reward mechanisms. The major neuronal type within the NAc is the GABAergic medium spiny neuron (MSN), whose activity is regulated by dopaminergic inputs. We previously reported that genetic deletion or pharmacological blockade of D3R increases GABAA α6 subunit in the ventral striatum. Here we tested the hypothesis that D3R-dependent changes in GABAA α6 subunit in the NAc affect voluntary alcohol intake, by influencing the inhibitory transmission of MSNs. We performed in vivo and ex vivo experiments in D3R knockout (D3R -/-) mice and wild type littermates (D3R +/+). Ro 15-4513, a high affinity α6-GABAA ligand was used to study α6 activity. At baseline, NAc α6 expression was negligible in D3R+/+, whereas it was robust in D3R-/-; other relevant GABAA subunits were not changed. In situ hybridization and qPCR confirmed α6 subunit mRNA expression especially in the NAc. In the drinking-in-the-dark paradigm, systemic administration of Ro 15-4513 inhibited alcohol intake in D3R+/+, but increased it in D3R-/-; this was confirmed by intra-NAc administration of Ro 15-4513 and furosemide, a selective α6-GABAA antagonist. Whole-cell patch-clamp showed peak amplitudes of miniature inhibitory postsynaptic currents in NAc medium spiny neurons higher in D3R-/- compared to D3R+/+; Ro 15-4513 reduced the peak amplitude in the NAc of D3R-/-, but not in D3R+/+. We conclude that D3R-dependent enhanced expression of α6 GABAA subunit inhibits voluntary alcohol intake by increasing GABA inhibition in the NAc.
Subject(s)
Binge Drinking/genetics , GABAergic Neurons/pathology , Receptors, Dopamine D3/genetics , Receptors, GABA-A/genetics , Animals , Binge Drinking/pathology , GABAergic Neurons/metabolism , Gene Expression Regulation , Male , Mice , Mice, Knockout , Nucleus Accumbens/metabolism , Nucleus Accumbens/pathology , Protein Subunits/genetics , RNA, Messenger/geneticsABSTRACT
In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At the molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression, which might be due to reduction in DNA methylation at the gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both the schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30â¯mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5â¯mg/kg/day), but not with haloperidol (0.6â¯mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.
Subject(s)
Cannabidiol/pharmacology , Methylazoxymethanol Acetate/pharmacology , Prenatal Exposure Delayed Effects/drug therapy , Schizophrenia/drug therapy , Amides , Animals , Arachidonic Acids/metabolism , Disease Models, Animal , Endocannabinoids/metabolism , Ethanolamines/metabolism , Female , Glycerides/metabolism , Hippocampus/metabolism , Interpersonal Relations , Male , Motor Activity/drug effects , Oleic Acids/metabolism , Palmitic Acids/metabolism , Piperidines/pharmacology , Polyunsaturated Alkamides/metabolism , Prefrontal Cortex/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Puberty , Pyrazoles/pharmacology , RNA, Messenger/metabolism , Rats , Receptor, Cannabinoid, CB1/metabolism , Recognition, Psychology/drug effects , Schizophrenia/chemically induced , Schizophrenia/metabolismABSTRACT
O objetivo do estudo foi avaliar o grau de dependência dos idosos internados, conforme o sistema de classificação de pacientes; e identificar fatores relacionados à dependência dos pacientes para o cuidado de enfermagem. Delineamento transversal, com amostra de 161 pacientes idosos avaliados no início, meio e final da hospitalização, pela escala de classificação de pacientes. Identificou-se prevalência na classificação intermediária (52,2%); associação estatística significativa da faixa etária de 80 a 100 anos com as classes intermediária e semi-intensiva; 40% dos classificados com cuidados semi-intensivos tiveram o óbito como desfecho. O processo de envelhecimento deve determinar cuidados de enfermagem específicos para esse grupo populacional, garantindo a qualidade da assistência.
The study aimed to evaluate the degree of dependency of elderly inpatients, according to the classification system of patients, and to identify factors related to patient dependency to nursing care. Cross-sectional study with a sample of 161 elderly patients evaluated at the beginning, middle and end of hospitalization, according to the patient classification scale. It was identified a prevalence in the intermediate rating (52.2%); statistically significant association between the ages of 80 to 100 years with the middle and semi-intensive classes; 40% of the elderly classified to the semi-intensive care had death as the outcome. The aging process must determine specific nursing care for this population group, ensuring the quality of care.
El objetivo del estudio fue evaluar el grado de dependencia de los ancianos hospitalizados, de acuerdo con el sistema de clasificación de pacientes, e identificar los factores relacionados con la dependencia del paciente a la atención de enfermería. Estudio transversal con una muestra de 161 pacientes de edad avanzada evaluados al inicio, mitad y final de la hospitalización, con la escala de clasificación de pacientes. Fue identificada prevalencia en la clasificación intermedia (52,2%); se encontró asociación estadísticamente significativa entre las edades de 80 a 100 años y las clases medias y semi-intensivo; y 40% de los ancianos clasificados como de atención semi-intensiva tuvieran la muerte como resultado. El proceso de envejecimiento debe determinar los cuidados de enfermería específicos para este grupo de población, asegurando la calidad de la atención.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Activities of Daily Living , Geriatric Assessment , Hospitalization , Patients/classification , Cross-Sectional StudiesABSTRACT
The study aimed to evaluate the degree of dependency of elderly inpatients, according to the classification system of patients, and to identify factors related to patient dependency to nursing care. Cross-sectional study with a sample of 161 elderly patients evaluated at the beginning, middle and end of hospitalization, according to the patient classification scale. It was identified a prevalence in the intermediate rating (52.2%); statistically significant association between the ages of 80 to 100 years with the middle and semi-intensive classes; 40% of the elderly classified to the semi-intensive care had death as the outcome. The aging process must determine specific nursing care for this population group, ensuring the quality of care.
