scholarly journals Role of Infection and Immunity in Bovine Perinatal Mortality: Part 2. Fetomaternal Response to Infection and Novel Diagnostic Perspectives

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2102
Author(s):  
Paulina Jawor ◽  
John F. Mee ◽  
Tadeusz Stefaniak
Keyword(s):  
Perinatal Mortality ◽  
Inflammatory Responses ◽  
Intrauterine Infection ◽  
Organ Damage ◽  
Diagnostic Methods ◽  
Organ Injury ◽  
Fetal Mortality ◽  
Phase Reaction ◽  
Bovine Fetuses ◽  
Analytical Approaches

Bovine perinatal mortality due to infection may result either from the direct effects of intrauterine infection and/or the fetal response to such infection, leading to the fetal inflammatory response syndrome (FIRS). Both intrauterine infection and FIRS, which causes multi-organ damage and involution of immune organs, compromise fetal survivability, sometimes fatally. Organ injury associated with FIRS may, in addition to causing fetal mortality, irreversibly compromise extrauterine adaptation of the neonate, a recognized problem in human fetuses. Diagnosis of intrauterine infection and of FIRS requires related, but independent analytical approaches. In addition to detection of pathogens, the immune and inflammatory responses of the bovine fetus may be utilized to diagnose intrauterine infection. This can be done by detection of specific changes in internal organs and the measurement of antibodies and/or elements of the acute phase reaction. Currently our ability to diagnose FIRS in bovine fetuses and neonates is limited to research studies. This review focuses on both the fetomaternal response to infection and diagnostic methods which rely on the response of the fetus to infection and inflammatory changes, as well other methods which may improve diagnosis of intrauterine infection in cases of bovine perinatal mortality.

scholarly journals The role of adenosine 1a receptor signaling on GFR early after the induction of sepsis

2018 ◽  
Vol 314 (5) ◽  
pp. F788-F797
Author(s):  
Jonathan M. Street ◽  
Erik H. Koritzinsky ◽  
Tiffany R. Bellomo ◽  
Xuzhen Hu ◽  
Peter S. T. Yuen ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Cumulative Effect ◽  
Organ Damage ◽  
Tubuloglomerular Feedback ◽  
Organ Injury ◽  
Sodium Reabsorption ◽  
Wild Type

Sepsis and acute kidney injury (AKI) synergistically increase morbidity and mortality in the ICU. How sepsis reduces glomerular filtration rate (GFR) and causes AKI is poorly understood; one proposed mechanism includes tubuloglomerular feedback (TGF). When sodium reabsorption by the proximal tubules is reduced in normal animals, the macula densa senses increased luminal sodium chloride, and then adenosine-1a receptor (A1aR) signaling triggers tubuloglomerular feedback, reducing GFR through afferent arteriole vasoconstriction. We measured GFR and systemic hemodynamics early during cecal ligation and puncture-induced sepsis in wild-type and A1aR-knockout mice. A miniaturized fluorometer was attached to the back of each mouse and recorded the clearance of FITC-sinistrin via transcutaneous fluorescence to monitor GFR. Clinical organ injury markers and cytokines were measured and hemodynamics monitored using implantable transducer telemetry devices. In wild-type mice, GFR was stable within 1 h after surgery, declined by 43% in the next hour, and then fell to less than 10% of baseline after 2 h and 45 min. In contrast, in A1aR-knockout mice GFR was 37% below baseline immediately after surgery and then gradually declined over 4 h. A1aR-knockout mice had similar organ injury and inflammatory responses, albeit with lower heart rate. We conclude that transcutaneous fluorescence can accurately monitor GFR and detect changes rapidly during sepsis. Tubuloglomerular feedback plays a complex role in sepsis; initially, TGF helps maintain GFR in the 1st hour, and over the subsequent 3 h, TGF causes GFR to plummet. By 18 h, TGF has no cumulative effect on renal or extrarenal organ damage.

scholarly journals PCSK9 and the Gut-Liver-Brain Axis: A Novel Therapeutic Target for Immune Regulation in Alcohol Use Disorder

2021 ◽  
Vol 10 (8) ◽  
pp. 1758
Author(s):  
Ji Soo Lee ◽  
Emma M. O’Connell ◽  
Pal Pacher ◽  
Falk W. Lohoff
Keyword(s):  
Alcohol Use ◽  
Therapeutic Target ◽  
Alcohol Use Disorder ◽  
Inflammatory Responses ◽  
Density Lipoprotein ◽  
Organ Damage ◽  
Brain Inflammation ◽  
Organ Injury ◽  
Chronic Alcohol ◽  
Novel Therapeutic

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to control or stop alcohol intake and is associated with organ damage including alcohol-associated liver disease (ALD) and progressive neurodegeneration. The etiology of AUD is complex, but organ injury due to chronic alcohol use can be partially attributed to systemic and local inflammation along the gut-liver-brain axis. Excessive alcohol use can result in translocation of bacterial products into circulation, increased expression of pro-inflammatory cytokines, and activation of immune cells, including macrophages and/or microglia in the liver and brain. One potential mediator of this alcohol-induced inflammation is proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is primarily known for its regulation of plasma low-density lipoprotein cholesterol but has more recently been shown to influence inflammatory responses in the liver and brain. In rodent and post-mortem brain studies, chronic alcohol use altered methylation of the PCSK9 gene and increased expression of PCSK9 in the liver and cerebral spinal fluid. Additionally, PCSK9 inhibition in a rat model of ALD attenuated liver inflammation and steatosis. PCSK9 may play an important role in alcohol-induced pathologies along the gut-liver-brain axis and may be a novel therapeutic target for AUD-related liver and brain inflammation.

scholarly journals Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nan Xiao ◽  
Meng Nie ◽  
Huanhuan Pang ◽  
Bohong Wang ◽  
Jieli Hu ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
Fatal Outcome ◽  
Organ Injury ◽  
Cytokine Release ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear

AbstractCytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.

Perinatal Profile of Twin Pregnancies: A Retrospective Review of 11 Years (1969–1979) at Hôpital Notre-Dame, Montréal, Canada

1982 ◽  
Vol 31 (3-4) ◽  
pp. 157-163 ◽  
Author(s):  
Marie-Françoise Desgranges ◽  
Xavier De Muylder ◽  
Jean-Marie Moutquin ◽  
Francisco Lazaro-Lopez ◽  
Bernard Leduc
Keyword(s):  
Perinatal Mortality ◽  
Perinatal Care ◽  
Fetal Mortality ◽  
Ultrasound Technique ◽  
Intrauterine Growth ◽  
Before And After ◽  
The Impact ◽  
Second Period ◽  
Twin Pregnancies ◽  
Main Factor

Four hundred and thirty four twins occurring in 220 women were studied during a period of 11 years (1969–1979) at Notre-Dame Hospital.Perinatal mortality (< 28 days) was compared before and after 1974, and the impact of ultrasound technique upon perinatal outcome was assessed during the second period (1974–1979). The main factor associated with perinatal mortality was low birth weight caused by either prematurity or intrauterine growth retardation.While fetal mortality remained unchanged within the two study periods, neonatal mortality decreased from 68.2/1,000 to 28.9/1,000 mainly due to increased survival rate of twins below 1,500 g at birth.With identical perinatal care during the same period, perinatal mortality and incidence of intrauterine growth-retarded twins remained unchanged despite early diagnosis by ultrasound.

scholarly journals Survival and Pulmonary Injury After Neonatal Sepsis: PD1/PDL1's Contributions to Mouse and Human Immunopathology

2021 ◽  
Vol 12 ◽  
Author(s):  
Eleanor A. Fallon ◽  
Chun-Shiang Chung ◽  
Daithi S. Heffernan ◽  
Yaping Chen ◽  
Monique E. De Paepe ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Intrauterine Infection ◽  
Organ Injury ◽  
Experimental Sepsis ◽  
Neonatal Mice ◽  
Neonatal Lung ◽  
Healthcare Crisis ◽  
Septic Neonate ◽  
Zona Occludens ◽  
The Impact

Morbidity and mortality associated with neonatal sepsis remains a healthcare crisis. PD1−/− neonatal mice endured experimental sepsis, in the form of cecal slurry (CS), and showed improved rates of survival compared to wildtype (WT) counterparts. End-organ injury, particularly of the lung, contributes to the devastation set forth by neonatal sepsis. PDL1−/− neonatal mice, in contrast to PD1−/− neonatal mice did not have a significant improvement in survival after CS. Because of this, we focused subsequent studies on the impact of PD1 gene deficiency on lung injury. Here, we observed that at 24 h post-CS (but not at 4 or 12 h) there was a marked increase in pulmonary edema (PE), neutrophil influx, myeloperoxidase (MPO) levels, and cytokine expression sham (Sh) WT mice. Regarding pulmonary endothelial cell (EC) adhesion molecule expression, we observed that Zona occludens-1 (ZO-1) within the cell shifted from a membranous location to a peri-nuclear location after CS in WT murine cultured ECs at 24hrs, but remained membranous among PD1−/− lungs. To expand the scope of this inquiry, we investigated human neonatal lung tissue. We observed that the lungs of human newborns exposed to intrauterine infection had significantly higher numbers of PD1+ cells compared to specimens who died from non-infectious causes. Together, these data suggest that PD1/PDL1, a pathway typically thought to govern adaptive immune processes in adult animals, can modulate the largely innate neonatal pulmonary immune response to experimental septic insult. The potential future significance of this area of study includes that PD1/PDL1 checkpoint proteins may be viable therapeutic targets in the septic neonate.

scholarly journals Laboratory Markers in the Management of Pediatric Polytrauma: Current Role and Areas of Future Research

2021 ◽  
Vol 9 ◽  
Author(s):  
Birte Weber ◽  
Ina Lackner ◽  
Christian Karl Braun ◽  
Miriam Kalbitz ◽  
Markus Huber-Lang ◽  
...  
Keyword(s):  
Imaging Techniques ◽  
Lactate Concentration ◽  
Organ Damage ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Organ Injury ◽  
Future Research ◽  
Acid Base Balance ◽  
Early Assessment ◽  
Laboratory Markers

Severe trauma is the most common cause of mortality in children and is associated with a high socioeconomic burden. The most frequently injured organs in children are the head and thorax, followed by the extremities and by abdominal injuries. The efficient and early assessment and management of these injuries is essential to improve patients' outcome. Physical examination as well as imaging techniques like ultrasound, X-ray and computer tomography are crucial for a valid early diagnosis. Furthermore, laboratory analyses constitute additional helpful tools for the detection and monitoring of pediatric injuries. Specific inflammatory markers correlate with post-traumatic complications, including the development of multiple organ failure. Other laboratory parameters, including lactate concentration, coagulation parameters and markers of organ injury, represent further clinical tools to identify trauma-induced disorders. In this review, we outline and evaluate specific biomarkers for inflammation, acid-base balance, blood coagulation and organ damage following pediatric polytrauma. The early use of relevant laboratory markers may assist decision making on imaging tools, thus contributing to minimize radiation-induced long-term consequences, while improving the outcome of children with multiple trauma.

scholarly journals Expression Levels of Candidate Circulating microRNAs in Early-Onset Neonatal Sepsis Compared With Healthy Newborns

2018 ◽  
Vol 11 ◽  
pp. 117863101879707 ◽  
Author(s):  
Benet B Dhas ◽  
Vijaya R Dirisala ◽  
B Vishnu Bhat
Keyword(s):  
Neonatal Sepsis ◽  
Inflammatory Responses ◽  
Diagnostic Techniques ◽  
Diagnostic Methods ◽  
Large Sample Size ◽  
Case Control Studies ◽  
Circulating Micrornas ◽  
Expression Levels ◽  
Sepsis Diagnosis ◽  
Low Sensitivity

The high mortality rate of neonatal sepsis is directly connected with time-consuming diagnostic methods that have low sensitivity and specificity. The need of the hour is to develop novel diagnostic techniques that are rapid and more specific. In this study, we estimated the expression levels of circulating microRNAs (miRNAs) that are involved in regulating immune response genes and underlying inflammatory responses, which may be used for sepsis diagnosis. The total circulating miRNA was isolated and the candidate miRNAs (miR-132, miR-146a, miR-155, and miR-223) were quantified by real-time polymerase chain reaction technique. Statistical analysis revealed that miR-132 ( P < .01) and miR-223 ( P < .05) were downregulated in septic newborns compared with healthy babies. The decrease in expression of miR-132 and miR-223 may be associated with increased expression of immune-related genes involved in TLR (Toll-like receptor) signaling pathway. Further case-control studies with large sample size are required to identify the potential of miRNAs in neonatal sepsis diagnosis.

scholarly journals Different experimental multiple trauma models induce comparable inflammation and organ injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Borna Relja ◽  
Bing Yang ◽  
Katrin Bundkirchen ◽  
Baolin Xu ◽  
Kernt Köhler ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Multiple Trauma ◽  
Inflammatory Cells ◽  
Organ Damage ◽  
Organ Injury ◽  
Local Inflammatory Response ◽  
Healthy Control ◽  
Post Traumatic ◽  
Tissue Trauma ◽  
Trauma Group

AbstractMultiple injuries appear to be a decisive factor for experimental polytrauma. Therefore, our aim was to compare the inflammatory response and organ damage of five different monotrauma with three multiple trauma models. For this, mice were randomly assigned to 10 groups: Healthy control (Ctrl), Sham, hemorrhagic shock (HS), thoracic trauma (TxT), osteotomy with external fixation (Fx), bilateral soft tissue trauma (bsTT) or laparotomy (Lap); polytrauma I (PT I, TxT + HS + Fx), PT II (TxT + HS + Fx + Lap) and one multi-trauma group (MT, TxT + HS + bsTT + Lap). The inflammatory response and organ damage were quantified at 6 h by analyses of IL-6, IL-1β, IL-10, CXCL1, SAA1, HMGB1 and organ injury. Systemic IL-6 increased in all mono and multiple trauma groups, while CXCL1 increased only in HS, PT I, PT II and MT vs. control. Local inflammatory response was most prominent in HS, PT I, PT II and MT in the liver. Infiltration of inflammatory cells into lung and liver was significant in all multiple trauma groups vs. controls. Hepatic and pulmonary injury was prominent in HS, PT I, PT II and MT groups. These experimental multiple trauma models closely mimic the early post-traumatic inflammatory response in human. Though, the choice of read-out parameters is very important for therapeutic immune modulatory approaches.

scholarly journals The Cytokine Network in the Critically Ill

1992 ◽  
Vol 20 (3) ◽  
pp. 288-302 ◽  
Author(s):  
R. Bellomo
Keyword(s):  
Septic Shock ◽  
Critical Illness ◽  
Critically Ill ◽  
Interleukin 1 ◽  
Endotoxic Shock ◽  
Organ Damage ◽  
Organ Injury ◽  
Blood Levels ◽  
Cytokine Network ◽  
Smooth Muscle Contractility

There is increasing experimental and clinical evidence that a number of cytokines play a major role in the response to injury and infection and in the development of organ damage in critically ill patients. Tumour necrosis factor (TNF) is now proposed to be a key mediator of organ injury during sepsis. It is elevated early in the course of septic shock and high levels correlate with unfavourable outcome. In animals it can produce the effects of endotoxin. The prophylactic administration of anti-TNF antisera protects mice and rabbits from lethal effects of lipopolysaccharide. Interleukin-1 (IL-1) is an endogenous pyrogen which induces leukocytosis and muscle catabolism. It causes hypotension and tachycardia by reducing smooth muscle contractility. IL-1 receptor blockers have been shown to diminish mortality in experimental endotoxic shock. Interleukin-6 (IL-6) is a pyrogen and lymphocyte activator. It is the major stimulus to acute phase protein production by the liver. A recently described neutrophil-activating peptide (Interleukin-8; IL-8) may be involved in the pathogenesis of ARDS. High blood levels of IL-8 have been found in patients with septic shock. Platelet-derived growth factor (PDGF) has been shown to stimulate TNF production, leukocyte chemotaxis and pulmonary vasoconstriction in response to endotoxin. Other cytokines and growth factors have not yet been studied in critical illness. The cytokine network can be either protective or damaging. Its activation during critical illness triggers complex and still poorly understood interactions. A better comprehension of its role in protection from infection and in the pathogenesis of multiple organ failure may allow therapeutic manipulations aimed at minimising adverse effects while retaining immunological protection.

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