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The P2X7 is an adenosine triphosphate (ATP)-gated ion channel involved in several facets of immune activation and neuronal function through its importance in interleukin (IL)-1ß secretion. We hypothesized that blockade of P2X7 would prevent perinatal brain injury associated with exposure to intrauterine (IU) inflammation. Dams received 45 mg/kg of Brilliant Blue G (BBG), a specific P2X7 receptor (P2X7R) antagonist, on gestation day 17 (E17) prior to administration of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). Furthermore, we utilized embryo transfer experiments to delineate whether the P2X7 was the key mediator of IU inflammation-associated brain injury on maternal or fetal sides. In these experiments, P2X7-/- dams were embryo-transferred wild type embryos and wild type dams were embryo-transferred P2X7-/- embryos. In the mouse model of intrauterine inflammation, pharmacologic blockade of P2X7R reduced preterm birth rate, improved offspring performance on neuromotor tests as well as the dendritic arborization and density of cortical neurons. Embryo transfer experiments demonstrated the importance of maternal P2X7R in IU inflammation-mediated effects on offspring. Both genetic and pharmacologic blockade of IL-1ß signaling, by targeting maternal P2X7R, ameliorated perinatal brain injury following exposure to IU inflammation. Specific targeting of maternal P2X7R may provide a clinically useful tool to prevent both preterm birth and prematurity-associated perinatal brain injury, and further studies are urgently needed.
Assuntos
Lesões Encefálicas/prevenção & controle , Inflamação/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Corantes de Rosanilina/farmacologia , Animais , Córtex Cerebral/citologia , Feminino , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Gravidez , Complicações na Gravidez/induzido quimicamente , Nascimento Prematuro , Receptores Purinérgicos P2X7/genética , Processos de Determinação Sexual/fisiologiaRESUMO
Objective The objective of this study was to localize by neuroimaging the altered structural brain development of these offspring using an autism model of transgenic mice lacking contactin-associated protein-like 2 (Cntnap2). Materials and Methods Pregnant dams were randomly allocated to fructose solution (10% W/V) as only drinking fluid or water. Cntnap2 heterozygous (+/-) offspring from each group were euthanized at 6 months of age and their whole brains evaluated by magnetic resonance imaging. T2-weighted images were acquired to evaluate the volumes of 29 regions of interest involved in autism spectrum disorder (ASD) pathogenesis. Whole brains were washed and processed for Nissl staining. Mann-Whitney U test and one-way analysis of variance were used for statistical analysis (significance: p < 0.05). Results The corpus callosum, anterior commissure, and caudate putamen were significantly smaller in Cntnap2 (+/-) male offspring exposed to fructose. No brain alterations were found in the female counterparts. Nissl staining of the caudate putamen revealed higher neuronal cell count in the male fructose offspring. Female group revealed an increase in caudate putamen neuronal cell count. Conclusion Metabolic dysregulation in pregnancy alters fetal brain development in genetically predisposed offspring. This is consistent with findings in human studies and supports the role of intrauterine factors in the etiology of autism.
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Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/patologia , Encéfalo/embriologia , Encéfalo/patologia , Frutose/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Animais , Transtorno do Espectro Autista/genética , Modelos Animais de Doenças , Feminino , Desenvolvimento Fetal , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Gravidez , Distribuição Aleatória , Fatores SexuaisRESUMO
Abdominal wall and spinal soft tissue findings are frequently encountered on CT or MR imaging of the abdomen and pelvis. Many of these entities have specific imaging findings, for which a definitive diagnosis can be made without the need for further work up. These abdominal wall and spinal findings may be diagnostically challenging for sub-specialized abdominal radiologists who are unfamiliar with their appearance and appropriate management. This review article describes and illustrates pathognomonic or characteristic abdominal wall and spinal pathologies, which reside outside the abdominopelvic cavity. The cases selected all have findings that allow a confident diagnosis without further imaging or intervention. The cases presented include myonecrosis, intramuscular abscess, myositis, iliopsoas bursitis, Morel-Lavallée lesion, hydrocele of canal of Nuck, Klippel Trenaunay Weber syndrome, neurofibroma with target sign, perineural cysts, filum terminale lipoma, calvarial bone flap, transverse rectus abdominis muscle (TRAM) flap, liposuction, and hidradenitis suppurativa, among others. Although not all-encompassing, this paper will help abdominal radiologists to accurately diagnose a variety of abdominal and pelvic extra-cavitary soft tissue pathologies by identifying key radiologic findings.
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Parede Abdominal , Masculino , Humanos , Parede Abdominal/diagnóstico por imagem , Pelve , Retalhos Cirúrgicos , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: Off-label drug use (OLDU) refers to the prescription of a currently available and marketed medication for a use that has never been approved by the Food and Drug Administration (FDA). Misoprostol is one of the drugs which is used off-label. This drug, authorized for the treatment or prevention of peptic ulcers and other stomach disorders, is commonly used off-label for inducing labor or intrauterine device insertion. This research focuses on identifying the percentage of morbidity and mortality by off-label use of misoprostol; classifying the most common off-label misoprostol use in Tabuk hospitals; and determining the availability of policy and procedures behind prescribing the off-label misoprostol. MATERIALS AND METHODS: Retrospective observational study was carried out. Data were collected from patients' files for those admitted to the maternity wards in Tabuk Hospitals from March 2019 until September 2019. RESULTS: Approximately 53% of cases were diagnosed with missed abortion. The mean time for abortion after administering misoprostol was 20.7 ± 28.2h. About 76% of women had an indication of bleeding. Guidelines were not followed with respect to dosage regimen. The mean of hospital stay was 3 days. There were no significant complications associated with the administration of misoprostol. CONCLUSION: There is no policy and procedure available in the hospital regarding off-label use of misoprostol. Moreover, physicians have low adherence to the guideline in terms of dosage, interval, and route of administration for each indication in obstetrics and gynecology.
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Continuing education (CE) is a structured educational activity. Pharmacists must actively participate in CE and is an important part of developing the professional competency of pharmacists. This research focuses on measuring Saudi pharmacists' perception in CE, its impact on professional performance, and the barriers in CE. This was a cross-sectional study, conducted in 2020, using random sample of Saudi pharmacists working in all workplaces from different cities in Saudi Arabia using a questionnaire. The questionnaire consists of 15 questions that assess the perception of Saudi pharmacists toward CE and barriers that prevent them from CE. A total of 409 pharmacists participated in the study. Majority of pharmacists were working in government hospitals (48.4%) and have <2 years of practice experience (44.5%). More than 70% of respondents acknowledged that CE helps to increase their knowledge. The pharmacists mentioned that getting a certificate (23.37%) was the major reason for attending a CE event. The reasons that prevent respondents from attending live CE were cost and work responsibilities (23.59% and 24.57%, respectively). This study reported a subjective assessment of pharmacists' perception toward CE, their lifelong learning experience. Saudi pharmacists showed a great desire for CE because they believed that it greatly affects their professional performance.
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The purpose of this paper is to describe cross-sectional imaging anatomic and morphologic parameters of solid renal tumors that urologists and interventional radiologists need for precise management, review the commonly used terms and descriptors of those parameters, and suggest a comprehensive reporting system for detected masses.
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Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Radiologistas , Radiologia Intervencionista , UrologistasRESUMO
We investigated the mechanisms by which CD8+ T-cell trafficking in placenta contributes to perinatal brain injury by studying effects of maternal CD8+ T-cell depletion (DEP) in a mouse model of intrauterine inflammation (IUI). Maternal CD8+ T cells were depleted with anti-CD8+ antibodies. IUI was induced with lipopolysaccharide (LPS). DEP was confirmed using flow cytometry. Preterm birth rate was evaluated. Offspring neurologic sequelae were assessed by Nissl staining, immune arrays, confirmatory individual TaqMan® gene assays, and neurobehavioral tests. DEP did not significantly prevent LPS-induced preterm birth but improved neurobehavioral performance (P < .001) and increased cortical neuronal density (P < .05) in LPS-exposed pups compared to controls. These changes were associated with decreased CCL3 and CXCL10 and increased CCL5 in DEP LPS-exposed mice. We demonstrate that DEP reduces perinatal brain injury following IUI. This supports a role for maternal CD8+ T-cell trafficking in placenta in mediating perinatal brain injury separate from preterm birth mechanisms.
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Lesões Encefálicas/imunologia , Linfócitos T CD8-Positivos/imunologia , Inflamação/imunologia , Placenta/imunologia , Animais , Quimiocina CCL3/imunologia , Quimiocina CCL5/imunologia , Quimiocina CXCL10/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Lipopolissacarídeos/imunologia , Depleção Linfocítica/métodos , Camundongos , Neurônios/imunologia , Gravidez , Nascimento Prematuro/imunologiaRESUMO
Preterm birth is a major risk factor for adverse neurological outcomes in ex-preterm children, including motor, cognitive, and behavioral disabilities. N-acetyl-L-cysteine therapy has been used in clinical studies; however, it requires doses that cause significant side effects. In this study, we explore the effect of low dose N-acetyl-L-cysteine therapy, delivered using a targeted, systemic, maternal, dendrimer nanoparticle (DNAC), in a mouse model of intrauterine inflammation. Our results demonstrated that intraperitoneal maternal DNAC administration significantly reduced the preterm birth rate and altered placental immune profile with decreased CD8+ T-cell infiltration. Furthermore, we demonstrated that DNAC improved neurobehavioral outcomes and reduced fetal neuroinflammation and long-term microglial activation in offspring. Our study is the first to provide evidence for the role of CD8+ T-cell in the maternal-fetal interface during inflammation and further support the efficacy of DNAC in preventing preterm birth and prematurity-related outcomes.
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Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Dendrímeros/uso terapêutico , Inflamação/complicações , Nascimento Prematuro/tratamento farmacológico , Nascimento Prematuro/etiologia , Animais , Coeficiente de Natalidade , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Dendrímeros/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Recém-Nascido , Lipopolissacarídeos/imunologia , Camundongos , Microglia/imunologia , Microglia/metabolismo , Nanopartículas , Placenta/imunologia , Placenta/metabolismo , Gravidez , Saco Vitelino/imunologia , Saco Vitelino/metabolismoRESUMO
OBJECTIVE: Recent epidemiological studies reported an association between maternal intake of acetaminophen (APAP) and attention deficit hyperactivity disorder (ADHD) in their children. However, none of these studies demonstrated causality. Our objective was to determine whether exposure to APAP during pregnancy result in hyperkinetic dysfunctions in offspring, using a murine model. MATERIAL AND METHODS: Pregnant CD1 mice (N = 8/group) were allocated to receive by gavage either APAP (150 mg/kg/day, equivalent to the FDA-approved maximum human clinical dose), or 0.5% carboxymethylcellulose (control group), starting on embryonic day 7 until delivery. Maternal serum APAP and alanine transaminase (ALT) concentrations were determined by ELISA and kinetic colorimetric assays, respectively. Open field locomotor activity (LMA) in the 30-day old mouse offspring was quantified using Photobeam Activity System. Mouse offspring were then sacrificed, whole brains processed for magnetic resonance imaging (MRI; 11.7 Tesla magnet) and for neuronal quantification using Nissl stain. The association between APAP exposure and LMA in mouse offspring was analyzed using a mixed effects Poisson regression model that accounted for mouse offspring weight, gender, random selection, and testing time and day. We corrected for multiple comparisons and considered P<0.008 as statistically significant. RESULTS: Maternal serum APAP concentration peaked 30 minutes after gavage, reaching the expected mean of 117 µg/ml. Serum ALT concentrations were not different between groups. There were no significant differences in vertical (rearing), horizontal, or total locomotor activity between the two rodent offspring groups at the P level fixed to adjust for multiple testing. In addition, no differences were found in volumes of 29 brain areas of interest on MRI or in neuronal quantifications between the two groups. CONCLUSION: This study refutes that hypothesis that prenatal exposure to APAP causes hyperkinetic dysfunction in mouse offspring. Due to lack of accurate assessment of ADHD in murine models, our results should be taken with caution when compared to the reported clinical data.