Septic Inflammation Research Articles

Lysosomal cationic proteins as the basis of cellular and humoral immunity of animals: the role of neutrophil extracellular traps (NETs) in immune homeostasis (review)

Relevance. Lysosomal cationic proteins (LCP) of granulocytic leukocytes: elastase, cathepsin G, proteinase-3, calgranulin, cathelicidins, defensins, lactoferrin, protegrins are active against viruses, bacteria, fungi, protozoa. The issues of physiological regulatory, immune and pathological effects of LCP and their derivatives – neutrophil (heterophil) extracellular traps (NETs) on pathogens, healthy cellular and tissue structures of the body are noted.Results. The increment of LCP granulocytes is realized by: 1. merocrine type — by degranulation; 2. exocytosis and false degranulation, that is, the process of decationization of lysosomes containing granules of cationic proteins with apocrine or holocrine type of secretion. Decationization implements exocytosis of LCP, extrusion of intact lysosomes from the cell with LCP, and diffusion of LCP through the lysosome membrane. Lysosome degranulation reactions with LCP form phagolysosomes and initiate phagocytosis, lysosome decationization reactions with LCP ensure the formation and functions of NETs. NETs is formed by non-lytic (non-lytic) and lytic (lyzed) pathways in septic and aseptic inflammation, with the ontogenetic development of immune links. NETs is stereotypically formed intravascular during aseptic inflammation, oxidative stress and in a physiological regime, when granulocytes are stimulated by products of oxidative metabolism. Using a cytochemical test with a highly sensitive acid-base bromophenol blue indicator, subcellular and cellular manifestations of the physiological age-related immune activity of cationic proteins accumulated in granulocyte lysosomes were studied on the avian model organism (Aves), and nonspecific adaptive reactions (NAR) of vertebrates in early postnatal ontogenesis were studied. The basis for the formation of NAR is the relationship of groups of leukocytes (lymphocytes, monocytes and granulocytes) with the dynamics of their lysosomal cationic proteins. The method for calculating the level of activity and potential capabilities of granulocytes in phagocytic reactions and in the formation of .NETs includes indices characterizing the directions and intensity of immune reactions of granulocytes, taking into account the processes: 1. degranulation of lysosomes with LCP — in the initiation of the cellular phagocytic link; 2. decationization of lysosomes with LCP — in the initiation of extracellular traps involved in the implementation of the humoral link of immunity.

Temporal kinetics of serum amyloid A (SAA) concentration and identification of SAA isoforms in blood and synovial fluid of horses with experimentally induced septic arthritis, non-septic synovitis, and systemic inflammation.

Prompt diagnosis of equine septic arthritis is crucial for successful treatment. Serum amyloid A (SAA) has been suggested as a reliable biomarker. However, we previously found that synovial fluid SAA increases in nonaffected joints of horses with septic arthritis. We hypothesized that systemic SAA may leak into the nonaffected joints. If this is the case, we also hypothesized that locally produced joint SAA isoforms may be better candidates for septic arthritis biomarkers. Thus, our objectives were 1) to evaluate the temporal kinetics of systemic and synovial fluid SAA in horses with septic arthritis (n = 5), non-septic synovitis (n = 5), and systemic inflammation (n = 5), examining both affected and contralateral joints; and 2) investigate putative locally produced joint SAA isoforms and detect amino-acid differences between them. We confirmed that SAA increases significantly in synovial fluid in nonaffected joints of horses with systemic inflammation (≤352 mg/L), as well as in contralateral nonaffected joins in horses with septic arthritis (≤1,830 mg/L) compared to baseline at time 0 (<0.2 mg/L). We also identified a putative locally produced joint SAA peptide in synovial fluid (FGDSGHGAADSR) that differed in 1 amino acid from 2 systemic peptides found both in plasma and synovial fluid. The putative joint SAA isoform was present in joints of horses with both septic arthritis and systemic inflammation (ion intensities 104-106). Thus, the increase of synovial fluid SAA may be both due to the leakage of SAA from serum into joints and local production of joint SAA isoforms.

Non‐functional metastatic thyroid carcinoma with oesophageal invasion and ulceration in a cat

AbstractAn adult, male, neutered, domestic shorthair cat was presented with a 2‐month history of dysphagia and a movable cervical mass. Cytology of the cervical mass was consistent with carcinoma. Thoracic radiographs revealed pleural effusion, cardiomegaly, diffuse patchy interstitial pattern and pulmonary nodules. Fluid analysis of the pleural effusion was consistent with marked septic neutrophilic inflammation, and Pasteurella multocida was isolated. Contrast‐enhanced cervical and thoracic computed tomography scan revealed a cervical mass in the region of the right thyroid lobe, with circumferential invasion of the oesophageal wall and well‐defined pulmonary nodules consistent with distant metastases. Oesophago‐gastroscopy was performed and revealed a proximal, oesophageal, mural mass causing severe intraluminal obstruction. Humane euthanasia was elected. Postmortem examination with histology and immunohistochemistry confirmed a thyroid carcinoma with oesophageal invasion and pulmonary metastases. The oesophageal mucosa was extensively disrupted and ulcerated by the thyroid carcinoma. Additionally, echocardiogram and postmortem examination confirmed cardiomyopathy and congestive heart failure.

Enhancing Aseptic Inflammation Resolution with 1-(2-Ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl Propionate: A Novel β-Cyclodextrin Complex as a Therapeutic Agent.

The synthesized compound, 1-(2-ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl propionate (EPPP), and its 1:1 complex with β-cyclodextrin (EPPPβCD) have been characterized for the first time through a comprehensive suite of analytical methods. This study explores the therapeutic potential of EPPPβCD in modulating immune responses and accelerating the resolution of septic inflammation induced by chromium and vanadium ions in outbred male rats. The research highlights the significant impact of EPPPβCD on the dynamics of regulatory T lymphocytes (Tregs), notably causing a reduction in the CD4+CD25+ fractions at the onset of inflammation. This effect is attributed to the inhibition of Treg proliferation, which is crucial in hastening the resolution of inflammation. These findings underscore the potential of EPPPβCD as a promising therapeutic agent in controlling and mitigating inflammation mediated by heavy metal exposure, thereby offering a new avenue for the development of anti-inflammatory treatments.

Free radical fragmentation and oxidation in the polar part of lysophospholipids: Results of the study of blood serum of healthy donors and patients with acute surgical pathology

The interaction of reactive oxygen species with cell membrane lipids is usually considered in the context of lipid peroxidation in the nonpolar component of the membrane. In this work, for the first time, data were obtained indicating that damage to human cell membranes can occur in the polar part of lysophospholipids at the interface with the aqueous environment due to free radical fragmentation (FRF) processes. FRF products, namely 1-hexadecanoyloxyacetone (PAc) and 1-octadecanoyloxyacetone (SAc), were identified in human serum, and a GC-MS method was developed to quantify PAc and SAc.The content of FRF products in serum samples of 52 healthy donors was found to be in the range of 1.98–4.75 μmol/L. A linear regression equation, CPAc&SAc (μmol/L) = 0.51 + 0.064 × years, was derived to describe the relationship between age and content of FRF products. In 70 patients with acute surgical pathology in comparison with the control group of healthy donors, two distinct clusters with different concentration levels of FRF products were revealed. The first cluster: groups of 43 patients with various localized inflammatory-destructive lesions of hollow organ walls and bacterial translocation (septic inflammation) of abdominal cavity organs. These patients showed a 1.5–1.9-fold (p = 0.012) decrease in the total concentration of PAc and SAc in serum. In the second cluster: groups of 27 patients with ischemia-reperfusion tissue damage (aseptic inflammation), – a statistically significant increase in the concentration of FRF products was observed: in 2.2–4.0 times (p = 0.0001).The obtained data allow us to further understand the role of free-radical processes in the damage of lipid molecules. FRF products can potentially be used as markers of the degree of free-radical damage of hydroxyl containing phospholipids.

Clinical aspects of diagnosis and prognosis of acute necrotic pancreatitis

Aim - to evaluate diagnostic markers of acute pancreatitis. Materials and methods. The study was conducted in the period from 2014 to 2023 and was based on the assessment of the severity of acute pancreatitis (AP) in 237 patients. All patients were divided due to the severity of AP. Mild AP was detected in 85 (35.86%), moderate - in 90 (37.97%), severe - in 44 (18.56%), critical - in 18 (7.59%) patients. Also, two study groups were formed: the Group 1 (patients with mild and moderate AP) and the Group 2 (severe and critical AP). Results. The level of procalcitonin in the blood was increased in 29 (12.23%) patients of the Group 2 (severe and critical AP) and was &gt;2.0 ng/ml. Among them in 25 (86.2%) patients early surgical treatment was perfomed and septic inflammation was detected in operating room. Typical ultrasound signs of AP were in 207 (87.34%) patients. Correlation roots between amylase and diastase on the first day of illness were: r=0,71 in the Group 1 and r=0.73 in the Group 2. Conclusions. The diagnosis of AP should be based on a comparative evaluation of the results of instrumental, laboratory tests and clinical symptoms. Levels of PCT, amylase, blood glucose, and urine diastase together with other clinical parameters helped to confirm the diagnosis of AP on admission to the hospital in 162 (92.57%) and 54 (87.09%) patients of the Group 1 and the Group 2. PCT should be used to predict complications and evaluate the efficiency of antibacterial therapy. The study was performed in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee for all participants. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Electrospun Composites of Chitosan with Cerium Oxide Nanoparticles for Wound Healing Applications: Characterization and Biocompatibility Evaluation In Vitro and In Vivo.

Cerium oxide nanoparticles (CeONPs), as part of tissue regeneration matrices, can protect cells from reactive oxygen species and oxidative stress. In addition, they can influence the properties of the scaffold, including its electrospinnability and mechanical strength. In this work, we prepared electrospun fiber mats from a chitosan and polyethylene oxide blend (CS-PEO) with the addition of ceria nanoparticles (CS-PEO-CeONP). The addition of CeONPs resulted in a smaller fiber diameter and higher swelling compared to CS-PEO fiber mats. CeONP-modified fiber mats also had a higher Young's modulus due to the reinforcing effect of the nanoparticles. Both mats had comparable adhesion and cytocompatibility to mesenchymal stem cells, which had a more rounded morphology on CS-PEO-CeONP compared to elongated cells on the CS-PEO mats. Biocompatibility in an in vivo rat model showed no acute toxicity, no septic or allergic inflammation, and no rough scar tissue formation. The degradation of both mats passed the stage of matrix swelling. CS-PEO-CeONP showed significantly slower biodegradation, with most of the matrix remaining in the tissue after 90 days. The reactive inflammation was aseptic in nature with the involvement of multinucleated foreign-body type giant cells and was significantly reduced by day 90. CeONPs induced the formation of the implant's connective tissue capsule. Thus, the introduction of CeONPs influenced the physicochemical properties and biological activity of CS-PEO nanofiber mats.

Osteopontin Depletion in Nonhematopoietic Cells Improves Outcomes in Septic Mice by Enhancing Antimicrobial Peptide Production.

Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that nonhematopoietic but not hematopoietic Opn depletion improved septic outcomes. When compared with wild type mice, cohoused Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation and OPN neutralization assay showed that Opn depletion could reduce bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in wild type organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN-deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes.

Histone H3 posttranslational modified enzymes defined neutrophil plasticity and their vulnerability to IL-10 in the course of the inflammation

BackgroundNeutrophils are a heterogeneous population capable of antimicrobial functions associated with pre-activation/activation and tissue regeneration. The specific polarisation of immune cells is mediated by the modification of ‘chromatin landscapes’, which enables differentiated access and activity of regulatory elements that guarantee their plasticity during inflammation No specific pattern within histone posttranslational modifications (PTMs) controlling this plasticity has been identified.MethodsUsing the in vitro model of inflammation, reflecting different states of neutrophils from resting, pre-activated cells to activated and reducing tissue regeneration, we have analysed 11 different histone posttranslational modifications (PTMs), PTM enzymes associated with remodelling neutrophil chromatin, and H3K4me3 ChIP-Seq Gene Ontology analysis focusing on the processes related to histone PTMs. These findings were verified by extrapolation to adequate clinical status, using neutrophils derived from the patients with sepsis (systemic septic inflammation with LPS-stimulated neutrophils), neuromyelitis optical spectrum disorders (aseptic inflammation with pre-activated neutrophils) and periodontitis (local self-limiting septic inflammation with IL-10-positive neutrophils).ResultsPhysiological activation of neutrophils comprises a pre-activation characterised by histone H3K27ac and H3K4me1, which position enhancers; direct LPS exposure is induced explicitly by H3K4me3 which marked Transcription Start Site (TSS) regions and low-level of H3K9me3, H3K79me2 and H3K27me3 which, in turn, marked repressed genes. Contrary to antimicrobial action, IL-10 positively induced levels of H3S10p and negatively H3K9me3, which characterised processes related to the activation of genes within heterochromatin mediated by CHD1 and H3K9me3 specific demethylase JMJD2A. IL-10 protects changes within histone PTMs induced by TNF or LPS that affected H3K4me3-specific methyltransferase SETD1A and MLL1. Neutrophils previously exposed to inflammatory factors become unvulnerable to IL-10 because previous LPS stimulation interrupts TSS regions marked by H3K4me3 of CHD1 and JMJD2A genes. Therefore, LPS-activated neutrophils are disabled to induce CHD1/JMJD2A enzymes by IL-10, making this process irreversible. Because transcription of JMJD2A and CHD1 also depends on TSS positioning by H3K4me3, neutrophils before LPS stimulation become insensitive to IL-10.ConclusionNeutrophils, once pre-activated by TNF or directly stimulated by LPS, become insensitive to the anti-inflammatory effects of IL-10, and vice versa; IL-10 protects neutrophils against these proinflammatory stimuli. This phenomenon is responsible for disturbing the natural process of resolving inflammation and tissue regeneration.Graphical

The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.

Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. SIGNIFICANCE STATEMENT: Invasive bacterial infections and sepsis are a major global health problem made worse by expanding antibiotic resistance, meaning better treatment options are urgently needed. Biomimetic cell-membrane-coated nanoparticles are an innovative therapeutic platform that deploys a multifaceted mechanism to action to neutralize microbial virulence factors, capture endotoxins, and bind excessive host proinflammatory cytokines, seeking to reduce host tissue injury, aid in microbial clearance, and improve patient outcomes.

PH Sensing for Early Detection of Septic Inflammation Based on Intrinsic Titanium β-Alloy Nanotubular Oxides

Orthopaedic surgeries like total hip and knee arthroplasty play a crucial role in restoring joint function for individuals with osteoarthritis. Deep bacterial infections are one of the most serious complications for orthopaedic implants. An infectious complication of an orthopaedic implant requires long-term and demanding treatment, often with repeated surgical procedures, and can lead to serious consequences such as implant failure, sepsis, and even death. Early detection of complications is of key importance for efficient therapy. The objective of this work is to investigate the possibilities of the nanotubular TiNbTa oxide for pH change sensing. Different surface treatments which lead to different surface natures were tested. For experiments, the inflammation was simulated by pH changes in the physiological solution. The response of the surface was monitored via the electrode potential changes. The results show that the nanotubular surface prepared on the TiNbTa alloy is a good possible candidate for pH sensing devices.

A reactive monocyte subset characterized by low expression of CD91 is expanded during sterile and septic inflammation.

This study was undertaken to assess CD91 expression on monocytes and changes in monocyte subset distribution during acute tissue damage and bloodstream infection (BSI). We investigated blood specimens from healthy individuals, trauma and cardiac surgery patients as a model of tissue damage, and patients with BSI, by flow cytometry using a panel of antibodies comprising CD45, HLA-DR, CD14, CD16 and CD91 for the identification of monocyte subsets. While infrequent in healthy subjects, CD91low/neg monocyte levels were markedly high in BSI, trauma and after cardiac surgery. This monocyte subset expanded up to15-fold in both patient cohorts, whereas CD14+CD16+ inflammatory monocytes were multiplied by a factor of 5 only. CD14+CD91low monocytes displayed a significantly lower density of HLA-DR and markedly reduced expression of CD300e, compared to the other subsets. They also expressed high levels of myeloperoxidase and showed robust phagocytic and oxidative burst activity. Expansion of CD91low monocytes is a sensitive marker of acute inflammatory states of infectious and non-infectious etiology.

Electroacupuncture targeting the immune system to alleviate sepsis

Sepsis is a life-threatening inflammatory syndrome with high morbidity and mortality rates. However, options for sepsis are still limited to general treatment in intensive care units (ICUs), and effective therapies that improve sepsis survival are required. Immune disturbances play a vital role in the pathology of sepsis and are associated with protracted inflammation, susceptibility to infections, and death. Therefore, many investigators have focused on the potential benefits of immunomodulation therapy for sepsis. Electroacupuncture (EA) has been practiced in clinics for many years and has shown advantages in treating infectious diseases. Over the last few decades, our understanding of the efficacy and mechanisms of EA in sepsis has undergone considerable developments. We searched the literature regarding “CNKI, Wan Fang Data, VIP Database, PubMed, and Ingenta Connect” from 2010 to 2023, using the keywords “sepsis” “septic” and “electroacupuncture” and 336 sources were searched. Finally, we included 82 studies that targeted the immune system to determine EA’s anti-inflammatory and immunomodulatory effects on sepsis. In this review, we found that EA has clinical benefits in relieving septic inflammation, improving immune function, and attenuating related multi-organ injury through several mechanisms, such as activation of the cholinergic anti-inflammatory pathway (CAP), vagal-adrenal axis, inhibition of the nuclear factor Kappa-B (NF-κB) signaling pathway, signal transducers and activators of transcription (STAT) signaling pathway, and improvement of immune cell function. Therefore, EA may be a promising complementary therapy for sepsis treatment. We also expect these data will contribute to further studies on EA in sepsis.

Investigation of the protective activity of baicalein on the lungs via regulation of various cellular responses in rats exposed to experimental sepsis.

In the present study, a cecal ligation and puncture (CLP)-induced experimental sepsis rat model was used to explore the effects of baicalein on inflammatory cytokine levels and oxidative stress as well as the possible regulatory role of nuclear factor-kappa B (NF-κB). For that purpose, 42 Wistar albino rats were equally divided into control, sham, sepsis, B50+S, B100+S, S+B50, and S+B100 groups. The B50+S and B100+S groups received baicalein before the induction of sepsis, while the S+B50 and S+B100 groups received baicalein afterwards. Experimental sepsis in related groups is generated through ligation of cecum and a puncture in cecal wall. Serum samples were used for tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) analyses, and tissue Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione (GSH), IL-6, and NF-κB levels were measured. Compared to the control group, there were significantly increases in the serum TNF-α, IL-6, tissue MDA, and NF-κB levels and decreases in the tissue SOD and GSH levels in the septic group (P<0.05). Compared to the septic group, inflammation and oxidative stress were reduced in the baicalein-treated groups. Although all of the pre- and post-treatment protocols alleviated inflammation and oxidative stress to varying degrees, pre-treatment with 100mg/kg was the most successful. Findings of this study indicated that baicalein has the potential to reduce sepsis-related oxidative stress and inflammation in the lungs and that pathological outcomes could be regulated via NF-κB transcription factor activity.

Visualizing neutrophil extracellular traps in septic equine synovial and peritoneal fluid samples using immunofluorescence microscopy.

Septic synovitis and peritonitis are routinely diagnosed in horses based on clinical examination findings and laboratory assessment of synoviocentesis and abdominocentesis samples, respectively. Diagnosis is difficult in some cases because of an overlap in laboratory results for septic and non-septic inflammation. Neutrophil extracellular trap (NET) formation is part of the innate immune response against pathogens. Identifying and quantifying NETs, which have not been explored in clinical samples from horses with septic synovitis and peritonitis, to our knowledge, may be helpful in detecting infectious processes. Our main objective was to determine whether NETs could be visualized in septic equine synovial and peritoneal fluid cytology samples using immunofluorescence with antibodies against citrullinated histone H3 (Cit-H3) and myeloperoxidase (MPO). We analyzed 9 synovial and 4 peritoneal fluid samples. NET percentages were quantified using a simple counting technique, which is suitable for high-quality, well-preserved, and stained cytospin smears. NETs were evident in all septic samples and were absent in a non-septic sample; NETs were better visualized with Cit-H3 than with MPO immunolabeling. Overall, we believe that there is the potential for NETs and associated markers to be used to investigate and understand septic inflammation in horses.

Septic inflammation of the bicipital bursa: clinical, imaging, and surgical findings in nine horses.

To describe the etiologies, clinicopathologic findings, diagnostic modalities employed, treatments, and outcome associated with cases of septic bicipital bursitis. 9 horses. Medical records of horses diagnosed with septic bicipital bursitis between 2000 and 2021 were reviewed. Horses were included if synoviocentesis of the bicipital bursa revealed a total nucleated cell count of ≥ 20,000 cells/µL with a neutrophil proportion of ≥ 80%, a total protein concentration of ≥ 4.0 g/dL, and/or the presence of bacteria on cytology, or positive culture of the synovial fluid. Information retrieved from medical records included signalment, history, clinicopathologic variables, diagnostic imaging findings, treatment, and outcome. Trauma was the most common inciting cause (n = 6). Synoviocentesis using ultrasonographic guidance was performed in all cases and showed alterations consistent with septic synovitis. Radiography identified pathology in 5 horses, whereas ultrasonography identified pathology in all horses. Treatment consisted of bursoscopy (n = 6) of the bicipital bursa of which 1 was performed under standing sedation, through-and-through needle lavage (3), bursotomy (2), or medical management alone (2). Five (55.6%) horses survived to discharge. Long-term follow-up was available for 3 horses and all were serviceably sound, with 2 in training as pleasure horses and 1 case continuing retirement. Ultrasonography was the most informative imaging modality and paramount in obtaining synovial fluid samples for definitive diagnosis of septic bicipital bursitis. Bursoscopy performed under standing sedation is a feasible treatment option. Horses treated for bicipital septic bursitis have a fair prognosis for survival and may return to some level of athletic performance.

Mammary gland inflammation in rabbits does (Oryctolagus cuniculus): A systematic review.

Mastitis is a common condition in rabbit (Oryctolagus cuniculus) does, especially in rabbitries where mammae inflammations are the leading pathological expression of Staphylococcus aureus infections in reproductive females. It affects both the litter and the lactating female, including subsequent lactations. Non-septic (i.e. galactostasis and cystic mastitis) and septic (i.e. Mastitis acuta; including Mastitis gangrenosa; and Mastitis chronica) mammary inflammations are acknowledged; however, the literature is scarce regarding non-septic inflammations or subclinical mastitis. Thus, the present systematic review highlights and summarizes the existing data concerning mastitis in rabbit does, including diagnosis and treatment plans.

Severe necrotizing soft tissue infections-Is wound microbiology a prognostic factor for clinical outcome?

Necrotizing soft tissue infections (NSTIs) represent similar pathophysiological features, but the clinical course might range from subacute to a rapidly progressive, fulminant sepsis. Initial wound microbiology is the base for the Guiliano classification. The timeline of microbiological colonization has not been described during the clinical course. The role of the different microbiological pathogens on the outcome and mortality is unclear. One hundred eighty patients were included with septic inflammation response syndrome on admission. Initial wound microbiology and the changes in wound microbiology were analysed during the clinical course and correlated with outcome and risk indicators. Overall mortality was 35%. Higher age, a high Charlson Comorbidity Index or ASA score and truncal infections were highly prognostic for a lethal outcome. Microbiological findings revealed significant differences in the persistence of bacteria during the course of disease. Streptococci were only detectable within the first 5 days, whereas other bacteria persisted over a longer period of time. Initial microbiological findings correlated with better prognosis when no causative agent was identified and for gram-negative rods. Varying survival rates were observed for different Streptococci, Staphylococci, Enterococci and other bacteria. The highest odds ratio for a lethal outcome was observed for Enterococci and fungi. Microbiological colonization changes during the clinical course of NSTIs and some microbiologic pathogens are predictive for worsening the outcome and survival. Streptococcus pyogenes is only detectable in the very early phase of NSTI and after 6 days not anymore detectable. Later Enterococci and fungi showed the highest odds ratios for a lethal outcome. Enterococci bacteria and fungi have yet not been considered of clinical relevance in NSTI or even as indicator for worsening the outcome.

Syndecan-4 is the key proteoglycan involved in mediating sepsis-associated lung injury

Vascular endothelial cell dysfunction involving syndecan (SDC) proteoglycans contributes to acute sepsis-associated lung injury (ALI), but the exact SDC isoform involved is unclear. We aimed to clarify which SDCs are involved in ALI. A relevant gene expression dataset (GSE5883) was analysed for differentially expressed genes (DEGs) between lipopolysaccharide (LPS)-treated and control lung endothelial cells and for SDC isoform expression. Bioinformatic analyses to predict DEG function were conducted using R language, Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes. SDC2 and SDC4 expression profiles were examined under inflammatory conditions in human lung vascular endothelial cell and mouse sepsis-associated ALI models. Transcription factors regulating SDC2/4 were predicted to indirectly assess SDC involvement in septic inflammation. Of the DEGs, 224 and 102 genes were up- and downregulated, respectively. Functional analysis indicated that DEGs were involved in modulating receptor ligand and signalling receptor activator activities, cytokine receptor binding, responses to LPS and molecules of bacterial origin, regulation of cell adhesion, tumour necrosis factor signalling, and other functions. DEGs were also enriched for cytoplasmic ribonucleoprotein granules, transcription regulator complexes, and membrane raft cellular components. SDC4 gene expression was 4.5-fold higher in the LPS group than in the control group, while SDC2 levels were similar in both groups. SDC4 mRNA and protein expression was markedly upregulated in response to inflammatory injury, and SDC4 downregulation severely exacerbated inflammatory responses in both in vivo and in vitro models. Overall, our data demonstrate that SDC4, rather than SDC2, is involved in LPS-induced sepsis-associated ALI.

Модели создания гнойно-септического воспаления большеберцовой кости у крысы для оценки действия биорезорбируемых материалов с антимикробными препаратами

Introduction A brief review of modeling purulent septic inflammation in rats, including with the help of an active bacterial agent, and methods for diagnosing inflammation are given. The aim of the study was to demonstrate the results of the development of an effective experimental model of purulent septic inflammation of the tibia in rats using minimally invasive methods for diagnosing infection in vivo. Materials and methods Various models of purulent septic inflammation were studied in four groups of small laboratory animals, when using the inoculation of Staphylococcus aureus. Methods for assessing purulent-septic inflammation that are not destructible by the object have been worked out: microbiological, tomographic, morphological. Results The results of the study indicate the possibility of creating experimental purulent-septic inflammation in rats by 14-60 days using S. aureus inoculation, which is a severe, rapidly progressive purulent infection that leads to extensive destruction of the bone with the formation of sequesters. Discussion To guarantee the formation of a purulent-inflammatory process of bone tissue in a shorter period of observation, a quantitatively controlled invasion of an active bacterial agent is necessary. A sclerosing agent and formation of a fistulous tract are not essential in creating inflammation. Conclusion The results of the development of experimental models for the creation of purulent-septic inflammation using minimally invasive in vivo diagnostic methods are demonstrated, which will allow an adequate assessment of the degree of infection before treatment.