scholarly journals Inflammatory Response to Different Toxins in Experimental Sepsis Models

2019 ◽  
Vol 20 (18) ◽  
pp. 4341 ◽  
Author(s):  
Kayle Dickson ◽  
Christian Lehmann
Keyword(s):  
Immune System ◽  
Host Response ◽  
Physiological Responses ◽  
Lipoteichoic Acid ◽  
Experimental Sepsis ◽  
Gram Negative ◽  
Mortality And Morbidity ◽  
Preclinical Drug Development ◽  
Life Threatening ◽  
Microcirculatory Disturbances

Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection. Despite serious mortality and morbidity, no sepsis-specific drugs exist. Endotoxemia is often used to model the hyperinflammation associated with early sepsis. This model classically uses lipopolysaccharide (LPS) from Gram-negative pathogens to activate the immune system, leading to hyperinflammation, microcirculatory disturbances and death. Other toxins may also be used to activate the immune system including Gram-positive peptidoglycan (PG) and lipoteichoic acid (LTA). In addition to these standard toxins, other bacterial components can induce inflammation. These molecules activate different signaling pathways and produce different physiological responses which can be taken advantage of for sepsis modeling. Endotoxemia modeling can provide information on pathways to inflammation in sepsis and contribute to preclinical drug development.

scholarly journals Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Maxime Bodinier ◽  
Estelle Peronnet ◽  
Karen Brengel-Pesce ◽  
Filippo Conti ◽  
Thomas Rimmelé ◽  
...  
Keyword(s):  
Immune System ◽  
Risk Stratification ◽  
Host Response ◽  
Surface Protein ◽  
Immunomodulatory Treatment ◽  
Early Risk ◽  
Hla Dr ◽  
Surface Protein Expression ◽  
Life Threatening ◽  
Over Time

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune system plays a key role in sepsis onset and remains dysregulated over time in a heterogeneous manner. Here, we decipher the heterogeneity of the first week evolution of the monocyte HLA-DR (mHLA-DR) surface protein expression in septic patients, a key molecule for adaptive immunity onset. We found and verified four distinctive trajectories endotypes in a discovery (n = 276) and a verification cohort (n = 102). We highlight that 59% of septic patients exhibit low or decreasing mHLA-DR expression while in others mHLA-DR expression increased. This study depicts the first week behavior of mHLA-DR over time after sepsis onset and shows that initial and third day mHLA-DR expression measurements is sufficient for an early risk stratification of sepsis patients. These patients might benefit from immunomodulatory treatment to improve outcomes. Going further, our study introduces a way of deciphering heterogeneity of immune system after sepsis onset which is a first step to reach a more comprehensive landscape of sepsis.

A Serological Storm

1970 ◽  
Vol 9 (2) ◽  
Author(s):  
Bertha Wong MD ◽  
Maria Bagovich MD ◽  
Ivan Blasutig PhD ◽  
Simon Carette MD MPhil
Keyword(s):  
Differential Diagnosis ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Clinical Context ◽  
Autoantibody Profile ◽  
Life Threatening ◽  
Clinically Significant ◽  
Sensory Polyneuropathy

This article describes a patient presenting with a sensory polyneuropathy and multiple autoantibodies, leading to the diagnosis of hepatitis C virus (HCV) infection. His widely positive autoantibody profile in the absence of clinically significant rheumatic disease illustrates the importance of interpreting autoimmune serology in the appropriate clinical context and the concept of HCV being a non-specific activator of the immune system. In addition, it highlights the importance of considering untreated HCV infection in the differential diagnosis of rheumatic complaints, particularly if the workup reveals multiple autoantibodies, as HCV is a potentially severe and life-threatening disease, which can be appropriately managed with effective antiviral therapy.

scholarly journals A novel chemical biology and computational approach to expedite the discovery of new-generation polymyxins against life-threatening Acinetobacter baumannii

2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  
Keyword(s):  
Public Health ◽  
Chemical Biology ◽  
Multidrug Resistant ◽  
Computational Approach ◽  
Gram Negative Bacteria ◽  
Global Public Health ◽  
Gram Negative ◽  
Life Threatening ◽  
New Generation ◽  
Novel Antibiotics

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.

scholarly journals Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tsukasa Tominari ◽  
Ayumi Sanada ◽  
Ryota Ichimaru ◽  
Chiho Matsumoto ◽  
Michiko Hirata ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bone Loss ◽  
Alveolar Bone ◽  
Osteoclast Differentiation ◽  
Lipoteichoic Acid ◽  
Alveolar Bone Loss ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

AbstractPeriodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

scholarly journals Evaluation of the Performance of Direct Susceptibility Test by VITEK-2 from Positively Flagged Blood Culture Broth for Gram-Negative Bacilli

2021 ◽  
Author(s):  
Kavipriya D. ◽  
Suman Susan Prakash ◽  
Sarumathi Dhandapani ◽  
Deepashree Rajshekar ◽  
Apurba Sankar Sastry
Keyword(s):  
Blood Culture ◽  
Susceptibility Testing ◽  
Blood Stream Infection ◽  
Tertiary Care ◽  
Reference Method ◽  
Culture Broth ◽  
Timely Initiation ◽  
Gram Negative ◽  
Mortality And Morbidity ◽  
Vitek 2

Abstract Background Timely initiation of antimicrobial therapy in patients with blood stream infection is absolutely necessary to reduce mortality and morbidity. Most clinical microbiology laboratories use conventional methods for identification and antimicrobial susceptibility testing (AST) that involve biochemical methods for identification followed by AST by disk diffusion. The aim of the current study is to assess the various errors associated with direct susceptibility testing done from blood culture broth using automated AST system-Vitek-2 compact compared with the reference method of AST done from bacterial colonies. Materials and Methods The study was conducted in a tertiary care public sector 2,200-bedded hospital in South India for a period of 6 months. The study involved positively flagged blood culture bottles that yielded single morphotype of Gram-negative organism by Gram stain. A total of 120 bacterial isolates were collected that consisted of consecutively obtained first 60 isolates of Enterobacteriaceae family (30 Escherichia coli and 30 Klebsiella pneumoniae) and consecutively obtained first 60 nonfermenters (30 Pseudomonas aeruginosa and 30 Acinetobacter baumannii). Vitek-2 AST was done from these 120 blood culture broth, following the protocol by Biomerieux, and results were obtained. Then, Vitek-2 was done from colonies (reference method) using appropriate panel for Enterobacteriaceae and nonfermenters, and results were obtained. Both the results were compared. Results Nonfermenters showed a better categorical agreement of 97.6%, as compared to Enterobacteriaceae, which showed 97%. Among Enterobacteriaceae, both E. coli and K. pneumoniae showed categorical agreement of 97% each. Conclusion The procedure of AST directly from blood culture broth represents a simple and effective technique that can reduce the turnaround time by 24 hours, which in turn benefits the clinician in appropriate utilization of antimicrobials for better patient care.

scholarly journals Epidemiology and outcome of sepsis in a tertiary-care hospital in a developing country

2005 ◽  
Vol 134 (2) ◽  
pp. 315-322 ◽  
Author(s):  
M. D. TANRIOVER ◽  
G. S. GUVEN ◽  
D. SEN ◽  
S. UNAL ◽  
O. UZUN
Keyword(s):  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Clinical Approach ◽  
Gram Negative Bacteria ◽  
Care Hospital ◽  
Gram Negative ◽  
Mortality And Morbidity ◽  
Underlying Diseases ◽  
Major Pathogens ◽  
Very High

Sepsis continues to have a substantial mortality and morbidity despite advances in the diagnosis and management of this condition. We retrospectively analysed hospital charts of patients diagnosed to have sepsis between January 2002 and June 2003. Demographic characteristics of patients, microbiological findings and predictors of survival were evaluated. Sixty-nine sepsis episodes that occurred in 63 patients were analysed. The most common underlying diseases were hypertension, malignancies and diabetes mellitus. Renal insufficiency, respiratory distress and disseminated intravascular coagulation developed in 52·2, 30·4 and 30·4% of the episodes respectively; 47·7% of the blood cultures yielded an organism. Gram-negative bacteria were the predominant microorganisms (65·9%). Fifty-five patients (87·3%) died. Mechanical ventilation and underlying renal disease were significant determinants of mortality. In conclusion, Gram-negative bacteria remain the major pathogens in sepsis. The mortality remains very high, and a change in the clinical approach to the septic patient should be employed to improve the outcome.

scholarly journals The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangtao Zheng ◽  
Weiwei Chen ◽  
Fangchen Gong ◽  
Ying Chen ◽  
Erzhen Chen
Keyword(s):  
Immune Response ◽  
Organ Dysfunction ◽  
Host Response ◽  
Therapeutic Targets ◽  
Host Immune Response ◽  
Unique Form ◽  
Pathogen Infection ◽  
Programmed Death ◽  
Life Threatening ◽  
Future Direction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.

scholarly journals Gram Positive Bacterial Lipoteichoic Acid Role in a Root Canal Infection – A Literature Review

2021 ◽  
Author(s):  
Vinoo Subramaniam Ramachandran ◽  
Mensudar Rathakrishnan ◽  
Malathy Balaraman Ravindrran ◽  
Alargarsamy Venkatesh ◽  
Vidhya Shankari Shanmugasundaram ◽  
...  
Keyword(s):  
Cell Wall ◽  
Immune Surveillance ◽  
Lipoteichoic Acid ◽  
The Body ◽  
Gram Positive ◽  
Gram Negative ◽  
Cell Wall Components ◽  
Root Canals ◽  
Endodontic Infection ◽  
Wall Components

Bacteria and its by-products are found to be the main cause of pulpal and periapical infection of tooth. Infected root canals of tooth harbours a wide variation of microbial flora that includes both Gram-positive and Gram-negative microorganisms. Bacterial components such as Lipopolysaccharide (LPS) of gram negative bacteria and Lipoteichoic Acid (LTA) of gram positive bacteria have the potential to enter the peri-apical tissue of tooth and initiate the inflammatory process. After microbial death that occurs either due to body’s defence cells or by antibiotic action, bacterial cell wall components such as LTA are released which can persist inside macrophages for prolonged periods causing chronic inflammation. Once these cell-wall components are recognized by the body immune surveillance cells, numerous inflammatory mediators are released leading to inflammation and subsequent pathological consequences. The purpose of this review is intend to summarize the role of gram positive bacterial component LTA in causing endodontic infection and use of potential therapeutic agents against LTA.

scholarly journals Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Wang ◽  
Ni Yang ◽  
Ri Wen ◽  
Chun-Feng Liu ◽  
Tie-Ning Zhang
Keyword(s):  
Host Response ◽  
Noncoding Rna ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Specific Treatment ◽  
Kidney Injury ◽  
Biological Processes ◽  
Immune Functions ◽  
Life Threatening ◽  
Organ Dysfunctions

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by a hyperinflammatory state accompanied by immunosuppression. Long noncoding RNAs (lncRNAs) are noncoding RNAs longer than 200 nucleotides and have important roles in mediating various biological processes. Recently, lncRNAs were found to exert both promotive and inhibitory immune functions in sepsis, thus participating in sepsis regulation. Additionally, several studies have revealed that lncRNAs are involved in sepsis-induced organ dysfunctions, including cardiovascular dysfunction, acute lung injury, and acute kidney injury. Considering the lack of effective biomarkers for early identification and specific treatment for sepsis, lncRNAs may be promising biomarkers and even targets for sepsis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in sepsis and sheds light on their use as potential biomarkers and treatment targets for sepsis.

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