The developing murine lung is susceptible to acetaminophen toxicity

2021 ◽  
Author(s):  
Evgenia Dobrinskikh ◽  
Laura G Sherlock ◽  
David Orlicky ◽  
Lijun Zheng ◽  
Robyn de Dios ◽  
...  
Keyword(s):  
Lung Injury ◽  
Neonatal Intensive Care ◽  
Perinatal Period ◽  
Antioxidant Response ◽  
Activity Level ◽  
Adult Mice ◽  
Cytokines And Chemokines ◽  
Toxic Exposures ◽  
Pro Inflammatory Cytokines

Acetaminophen (N-acetyl-p-aminophenol, APAP) use in the neonatal intensive care unit is rapidly increasing. While APAP-related hepatotoxicity is rarely reported in the neonatal literature, other end-organ toxicity can occur with toxic exposures. APAP-induced lung injury has been reported with toxic exposures in adults, but whether this occurs in the developing lung is unknown. Therefore, we tested whether toxic APAP exposures would injure the developing lung. Neonatal C57BL/6 mice (PN7, early alveolar stage of lung development) were exposed to a dose of APAP known to cause hepatotoxicity in adult mice (280 mg/kg, IP). This exposure induced significant lung injury in the absence of identifiable hepatic toxicity. This injury was associated with increased pulmonary expression of Cyp2e1, the xenobiotic enzyme responsible for the toxic conversion of APAP. Exposure was associated with increased pulmonary expression of antioxidant response genes and decreased pulmonary glutathione peroxidase activity level. Furthermore, we observed an increase in pulmonary expression of pro-inflammatory cytokines and chemokines. Lastly, we were able to demonstrate that this toxic APAP exposure was associated with a shift in pulmonary metabolism away from glycolysis with an increased oxidative phosphorylation, a finding consistent with increased mitochondrial workload, potentially leading to mitochondrial toxicity. This previously unrecognized injury and metabolic implications highlight the need to look beyond the liver and evaluate both the acute and long-term pulmonary implications of APAP exposure in the perinatal period.

NOISE LEVELS IN INFANT INCUBATORS (ADVERSE EFFECTS?)

PEDIATRICS ◽  
1974 ◽  
Vol 53 (1) ◽  
pp. 29-32
Author(s):  
Gösta Blennow ◽  
Nils W. Svenningsen ◽  
Bengt Almquist
Keyword(s):  
Neonatal Intensive Care ◽  
Perinatal Period ◽  
Noise Levels ◽  
Sound Levels ◽  
Different Types ◽  
High Sound ◽  
Perinatal Risk Factor ◽  
Infant Incubators

Certain environmental factors in neonatal intensive care have attracted large interest and have been studied thoroughly. However, less attention has been paid to the noise level inside infant incubators. The present study of four different types of incubators revealed high sound levels of 70 to 80 dB sound pressure level (SPL) at 125 Hz. Some infants are nursed in incubators for weeks or months and thereby exposed to these noise levels for an undue period of time. It is suggested that the high noise levels in infant incubators should be considered a perinatal risk factor with regard to later hearing impairment. It deserves more attention as hitherto, especially with consideration to the construction of incubators, but also in follow-up studies of long-term sequelae after an abnormal perinatal period.

Caspases and apoptosis

2002 ◽  
Vol 38 ◽  
pp. 9-19 ◽  
Author(s):  
Guy S Salvesen
Keyword(s):  
Cysteine Proteases ◽  
Signalling Pathways ◽  
Term Survival ◽  
Mature Adult ◽  
Intracellular Signalling Pathways ◽  
Adult Cell ◽  
Caspase Family ◽  
Cell Fragments ◽  
Pro Inflammatory Cytokines

The ability of metazoan cells to undergo programmed cell death is vital to both the precise development and long-term survival of the mature adult. Cell deaths that result from engagement of this programme end in apoptosis, the ordered dismantling of the cell that results in its 'silent' demise, in which packaged cell fragments are removed by phagocytosis. This co-ordinated demise is mediated by members of a family of cysteine proteases known as caspases, whose activation follows characteristic apoptotic stimuli, and whose substrates include many proteins, the limited cleavage of which causes the characteristic morphology of apoptosis. In vertebrates, a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways.

Improving Feeding Outcomes in the NICU: Moving From Volume-Driven to Infant-Driven Feeding

2010 ◽  
Vol 19 (3) ◽  
pp. 68-74 ◽  
Author(s):  
Catherine S. Shaker
Keyword(s):  
Intensive Care Unit ◽  
Dynamic Systems ◽  
Neonatal Intensive Care ◽  
Well Being ◽  
Dynamic Systems Theory ◽  
Feeding Problems ◽  
Care Giving ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Current research on feeding outcomes after discharge from the neonatal intensive care unit (NICU) suggests a need to critically look at the early underpinnings of persistent feeding problems in extremely preterm infants. Concepts of dynamic systems theory and sensitive care-giving are used to describe the specialized needs of this fragile population related to the emergence of safe and successful feeding and swallowing. Focusing on the infant as a co-regulatory partner and embracing a framework of an infant-driven, versus volume-driven, feeding approach are highlighted as best supporting the preterm infant's developmental strivings and long-term well-being.

Point of Care Neurosonogram in Neonates - Utility and Prognostic Value

2019 ◽  
Vol 2 ◽  
pp. 1
Author(s):  
Bhushita Lakhkar ◽  
M. M. Patil ◽  
Bhavana Lakhkar ◽  
Bhushan Lakhkar
Keyword(s):  
Neonatal Intensive Care ◽  
Point Of Care ◽  
Color Doppler ◽  
Periventricular Leukomalacia ◽  
Birth Asphyxia ◽  
Common Finding ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Doppler Study

Objective The study aimed to utilize the neurosonographic findings in neonates in early diagnosis, prediction of their long-term outcome, parental counseling, and early intervention. Methods The study was carried out in neonatal intensive care unit (NICU) of Shri BM Patil Medical College and Hospital. All preterms and term babies with neurological clinical findings were included in the study. Neurosonogram was done within first 7 days in preterms and when indicated in terms. Philips HD11XE ultrasound and color Doppler unit were used with a small footprint probe. Color Doppler images for vessels were performed for screening of vascular changes. Results A total of 215 babies were included, of which 80 (32%) were term and the rest were preterm. Mean weight of term babies was 2.8 kg and that of preterm was 1.2 kg.Among term babies, 78% showed ultrasound abnormality, and among preterm, 42%showed abnormalities. Among term babies, 60% and, among preterms, 30% had birth asphyxia. Periventricular leukomalacia was the most common and earliest finding followed by thalamic hyperechogenicity and intracranial hemorrhage. Intraventricular hemorrhage was more common in preterm babies. Other common finding in NICU was meningitis which was more common in pretrms. Among congenital anomalies, corpus callosal agenesis was more common. Conclusions Point of care ultrasonography along with Doppler study is very useful and safe to use in NICUs. It helps in diagnosis, patient management as well as prediction of many short- and long-term outcomes.

NF-κB as a Key Mediator of Brain Inflammation in Alzheimer’s Disease

2019 ◽  
Vol 18 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Chul Ju Hwang ◽  
Dong-Young Choi ◽  
Mi Hee Park ◽  
Jin Tae Hong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Strategies ◽  
Close Correlation ◽  
Specific Protein ◽  
Brain Inflammation ◽  
Cytokines And Chemokines ◽  
Inflammatory Drugs ◽  
Peptide Fibrils

Alzheimer’s disease is the most common form of dementia. It is characterized by betaamyloid peptide fibrils which are extracellular deposition of a specific protein, accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-κB is a family of redox sensitive transcriptional factors, and it is known that NF-κB has binding sites in the promoter region of the genes involved in amyloidogenesis and inflammation. Long-term use of non-steroidal anti-inflammatory drugs prevents progression of AD and delays its onset, suggesting that there is a close correlation between NF-κB and AD pathogenesis. This study aims to (1) assess the association between NF-κB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) review treatment strategies designed to treat or prevent AD with NF-κB inhibitors.

scholarly journals Minimum 10-Year Clinical Outcome of Lateral Collagen Meniscal Implants for the Replacement of Partial Lateral Meniscal Defects: Further Results From a Prospective Multicenter Study

2021 ◽  
Vol 9 (5) ◽  
pp. 232596712199491
Author(s):  
Alberto Grassi ◽  
Gian Andrea Lucidi ◽  
Giuseppe Filardo ◽  
Piero Agostinone ◽  
Luca Macchiarola ◽  
...  
Keyword(s):  
Survival Rate ◽  
Case Series ◽  
Final Analysis ◽  
Activity Level ◽  
Long Term Results ◽  
Level Of Evidence ◽  
Unicompartmental Knee Arthroplasties ◽  
Tegner Score

Background: The collagen meniscal implant (CMI) is a biologic scaffold aimed at replacing partial meniscal defects. The long-term results of lateral meniscal replacement have never been investigated. Purpose: To document the clinical outcomes and failures of lateral CMI implantation for partial lateral meniscal defect at a minimum 10-year follow-up. Study Design: Case series; Level of evidence, 4, Methods: This study included 24 consecutive patients who underwent lateral CMI implantation for partial lateral meniscal defects between April 2006 and September 2009 and who were part of a previous study with a 2-year follow-up. Outcome measures at the latest follow-up included the Lysholm score, Knee injury and Osteoarthritis Outcome Score, visual analog scale (VAS) for pain, Tegner activity level, and EuroQol 5-Dimensions score. Data regarding complications and failures were collected, and patients were asked about their satisfaction with the procedure. Results: Included in the final analysis were 19 patients (16 male, 3 female) with a mean age at surgery of 37.1 ± 12.6 years and a mean follow-up of 12.4 ± 1.5 years (range, 10-14 years). Five failures (26%) were reported: 1 CMI removal because of implant breakage and 4 joint replacements (2 unicompartmental knee arthroplasties and 2 total knee arthroplasties). The implant survival rate was 96% at 2 years, 85% at 5 years, 85% at 10 years, 77% at 12 years, and 64% at 14 years. Lysholm scores at the final follow-up were rated as “excellent” in 36% (5 of 14 nonfailures), “good” in 43% (6 of 14), and “fair” in 21% (3 of 14). The VAS score was 3.1 ± 3.1, with only 16% (3 of 19 patients) reporting that they were pain-free; the median Tegner score was 3 (interquartile range, 2-5). All clinical scores decreased from the 2-year follow-up; however, with the exception of the Tegner score, they remained significantly higher compared with the preoperative status. Overall, 79% of patients were willing to undergo the same procedure. Conclusion: Lateral CMI implantation for partial lateral meniscal defects provided good long-term results, with a 10-year survival rate of 85% and a 14-year survival rate of 64%. At the final follow-up, 58% of the patients had “good” or “excellent” Lysholm scores. However, there was a general decrease in outcome scores between the short- and the long-term follow-up.

scholarly journals When a Neonate Is Born, So Is a Microbiota

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 148
Author(s):  
Alessandra Coscia ◽  
Flaminia Bardanzellu ◽  
Elisa Caboni ◽  
Vassilios Fanos ◽  
Diego Giampietro Peroni
Keyword(s):  
Bacterial Colonization ◽  
Perinatal Period ◽  
Delivery Mode ◽  
Fetal Life ◽  
Assisted Reproduction Techniques ◽  
Neonatal Nutrition ◽  
Short And Long Term ◽  
Number Of Bacteria

In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one’s life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the “sterile womb”. Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject.

scholarly journals Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury

2019 ◽  
Vol 20 (7) ◽  
pp. 1678 ◽  
Author(s):  
Yi-Chen Lee ◽  
Chun-Yu Lin ◽  
Yen-Hsu Chen ◽  
Wen-Chin Chiu ◽  
Yen-Yun Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Cell Lines ◽  
Inflammatory Cytokines ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial ◽  
Epithelial Cell Lines ◽  
Nfκb Pathway ◽  
Pro Inflammatory Cytokines

Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NFκB pathway, and increased the expression of pro-inflammatory cytokines, including IL1-β, IL-6, and TNF-α in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NFκB pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.

scholarly journals Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne-Christine Plank ◽  
Stefan Frey ◽  
Lukas Andreas Basedow ◽  
Jalal Solati ◽  
Fabio Canneva ◽  
...  
Keyword(s):  
Stress Reactivity ◽  
Dorsal Hippocampus ◽  
Methylation Status ◽  
Stress Axis ◽  
Mrna Levels ◽  
Fk506 Binding Protein ◽  
Adult Mice ◽  
Stress Related Genes ◽  
Long Term Impact

AbstractIn our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

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