Infectious Inflammatory Diseases Research Articles

Milk fat globules as a source of microRNAs for mastitis detection

Mastitis is an infectious inflammatory disease in dairy cows, causing economic losses and reducing animal welfare. With the final aim of discovering early and easily accessible biomarkers, the objective of this study was to validate the use of milk fat globules (MFGs) as a source of small non-coding RNAs (microRNAs, miRNAs) to diagnose mastitis. We studied the abundance of six miRNAs known to be regulated in the mammary gland during inflammation, by comparing their abundance in MFGs from five cows before and after lipopolysaccharide (LPS) challenge. Among them, four (miR-494-3p, -148a-3p, -99a-5p, -125b-5p) were differentially abundant according to inflammatory status. Bioinformatics analyses showed that they are predicted to target genes regulating cell life (e.g.: apoptotic process, cell cycle) and genes involved in gene expression (e.g.: mRNA processing, translation). Network analyses revealed that they are also related to Interleukin signaling network, confirming the contribution of miRNAs to the inflammation response of the mammary gland. We demonstrated that MFGs might be an easy source of miRNAs that are potential biomarkers to detect early mastitis allowing the application of a rapid and effective treatment. However, before its exploitation to diagnose mastitis, investigation of MFGs of early spontaneous mastitis must validate the use of these miRNAs as biomarkers of early infection of the mammary gland.

Integrated N-glycoproteomics Analysis of Human Saliva for Lung Cancer.

Aberrant protein N-glycosylation is a cancer hallmark, which has great potential for cancer detection. However, large-scale and in-depth analysis of N-glycosylation remains challenging because of its high heterogeneity, complexity, and low abundance. Human saliva is an attractive diagnostic body fluid, while few efforts explored its N-glycoproteome for lung cancer. Here, we utilized a zwitterionic-hydrophilic interaction chromatography-based strategy to specifically enrich salivary glycopeptides. Through quantitative proteomics analysis, 1492 and 1234 intact N-glycopeptides were confidently identified from pooled saliva samples of 10 subjects in the nonsmall-cell lung cancer group and 10 subjects in the normal control group. Accordingly, 575 and 404 N-glycosites were revealed for the lung cancer group and normal control group. In particular, 154 N-glycosites and 259 site-specific glycoforms were significantly dysregulated in the lung cancer group. Several N-glycosites located at the same glycoprotein and glycans attached to the same N-glycosites were observed with differential expressions, including haptoglobin, Mucin-5B, lactotransferrin, and α-1-acid glycoprotein 1. These N-glycoproteins were mainly related to inflammatory responses, infectious diseases, and cancers. Our study achieved comprehensive characterization of salivary N-glycoproteome, and dysregulated site-specific glycoforms hold promise for noninvasive detection of lung cancer.

Abstract 3130: IL-27 signaling regulates anti-cancer immune response in hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is the most common form of liver cancer with poor survival and limited therapeutic options. HCC development is accompanied by underlying chronic inflammation, which represents a major unifying mechanism for tumor promotion. While some tumor-promoting inflammatory mechanisms had been proposed, the identity of immune mechanisms controlling anti-cancer immunity in HCC remain poorly understood. Interleukin (IL)-27 receptor signaling plays an anti-inflammatory role in a variety of infectious and chronic inflammatory diseases. Here, using genetic and pharmacological approaches we found that IL-27 receptor (IL-27R) signaling promotes HCC development in vivo. Genetic loss of IL-27R suppressed HCC in both carcinogen-induced and non-alcoholic steatohepatitis (NASH)-driven models. Mechanistically, the pro-tumorigenic effect was mediated by an immunoregulatory role of IL-27R within the tumor microenvironment, particularly the suppression of cytotoxic Natural killer (NK) cells. Single-cell RNA analysis further established the role of IL-27R signaling in restraining cytotoxic populations of NK cells. IL-27R ablation enhanced the accumulation and activation of cytotoxic NK cells during acute liver injury and in HCC tumors, while depletion or functional impairment of NK cells abrogated the effect of genetic IL-27R disruption. Taken together, our data suggest an unexpected role of IL-27R signaling as a novel immunological checkpoint regulating innate cytotoxic cell activity and promoting development of HCC of different etiologies. Citation Format: Aleksandra M. Mazitova, Turan Aghayev, Jennifer Fang, Amiran Dzutsev, Giorgio Trinchieri, Kerry S. Campbell, Sergei I. Grivennikov, Ekaterina K. Koltsova. IL-27 signaling regulates anti-cancer immune response in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3130.

ПАРАМЕТРЫ НЕТОЗА У ПАЦИЕНТОВ С СЕЛЕКТИВНЫМ ДЕФИЦИТОМ ИММУНОГЛОБУЛИНА А

Objective. To study NETosis parameters in patients with selective immunoglobulin A deficiency. Material and methods. We studied the features of NETosis in peripheral blood of 46 patients (21 males and 25 females, mean age 37±12.7 years) with a confirmed diagnosis of selective immunoglobulin A deficiency. Results. Аctivation of NETosis (NET30SP, NET30ST, NET150SP and NET150ST, р<0.001) was found in patients with selective IgA deficiency relative to the comparison group. The maximum degree of increase in leukocyte NETosis in patients was observed during short-term incubation of cells (NET30SP, NET30ST). The relationship between the level of NETosis and apoptosis of neutrophils has been revealed. The patients with a simultaneous activation of NETosis and superoxide anion production by neutrophils showed a higher incidence of combined clinical manifestations compared to patients with an isolated increase of NETosis (χ2=9.19; р=0.002). Conclusion. This study demonstrated that in patients with selective immunoglobulin A deficiency during remission of infectious inflammatory diseases, the ability of blood neutrophils to form extracellular networks in combination with the activation of other manifestations of neutrophils reactivity – superoxide anion-producing function and apoptosis – is increased.

Diagnostic value of estimation of cytokine status at the infectious­inflammatory diseases of vagina and neck of uterus

The results of the conducted researches testify to the substantial role of cytokine status at the estimation of the state of local factors of defence for patients with the infectious-inflammatory diseases of vagina and neck of uterus. The got results must be taken into account at development of algorithm of diagnostic and treatment-and-prophylactic measures.

Anti-apoptosis and anti-inflammation activity of circ_0097010 downregulation in lipopolysaccharide-stimulated periodontal ligament cells by miR-769-5p/Krüppel like factor 6 axis

Background/purposePeriodontitis is a prevalent infectious inflammatory disease. Growing evidence has revealed important roles for circular RNAs (circRNAs) and circRNA sponge activity in periodontitis. Here, we elucidated the precise part of circ_0097010 in periodontitis pathogenesis. Materials and methodsHuman periodontal ligament cells (hPDLCs) were exposed to lipopolysaccharide (LPS). Cell viability, proliferation and apoptosis were evaluated by CCK-8 assay, EdU incorporation assay and flow cytometry, respectively. Circ_0097010, microRNA (miR)-769-5p and Krüppel like factor 6 (KLF6) were quantified by qRT-PCR and Western blot. Interleukin 6 (IL-6) level, tumor necrosis factor-α (TNF-α) secretion, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were used to confirm the direct relationship between miR-769-5p and circ_0097010 or KLF6. ResultsOur data showed that LPS repressed cell proliferation and induced cell apoptosis and inflammation in hPDLCs. Circ_0097010 was upregulated in periodontitis samples and LPS-exposed hPDLCs. Downregulation of circ_0097010 exerted anti-apoptosis and anti-inflammation functions in LPS-exposed hPDLCs. Mechanistically, circ_0097010 acted as a miR-769-5p sponge, and reduced abundance of miR-769-5p reversed the anti-apoptosis and anti-inflammation effects of circ_0097010 suppression. KLF6 was a direct miR-769-5p target, and miR-769-5p-mediated inhibition of KLF6 possessed anti-apoptosis and anti-inflammation functions in LPS-induced hPDLCs. Moreover, circ_0097010 controlled KLF6 expression by miR-769-5p. ConclusionThese data identify circ_0097010 as a key regulator of LPS-induced inflammation and apoptosis in hPDLCs and highlight a novel mechanism of circ_0097010 regulation through miR-769-5p/KLF6 axis.

Role of thymic stromal lymphopoietin in allergy and beyond.

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that acts on multiple cell lineages, including dendritic cells, T cells, B cells, neutrophils, mast cells, eosinophils and innate lymphoid cells, affecting their maturation, survival and recruitment. It is best known for its role in promoting type 2 immune responses such as in allergic diseases and, in 2021, a monoclonal antibody targeting TSLP was approved for the treatment of severe asthma. However, it is now clear that TSLP has many other important roles in a variety of settings. Indeed, several genetic variants for TSLP are linked to disease severity, and chromosomal alterations in TSLP are common in certain cancers, indicating important roles of TSLP in disease. In this Review, we discuss recent advances in TSLP biology, highlighting how it regulates the tissue environment not only in allergic disease but also in infectious diseases, inflammatory diseases and cancer. Encouragingly, therapies targeting the TSLP pathway are being actively pursued for several diseases.

Trachoma.

Trachoma is a neglected tropical disease caused by infection with conjunctival strains of Chlamydia trachomatis. It can result in blindness. Pathophysiologically, trachoma is a disease complex composed of two linked chronic processes: a recurrent, generally subclinical infectious-inflammatory disease that mostly affects children, and a non-communicable, cicatricial and, owing to trichiasis, eventually blinding disease that supervenes in some individuals later in life. At least 150 infection episodes over an individual's lifetime are needed to precipitate trichiasis; thus, opportunity exists for a just global health system to intervene to prevent trachomatous blindness. Trachoma is found at highest prevalence in the poorest communities of low-income countries, particularly in sub-Saharan Africa; in June 2021, 1.8 million people worldwide were going blind from the disease. Blindness attributable to trachoma can appear in communities many years after conjunctival C. trachomatis transmission has waned or ceased; therefore, the two linked disease processes require distinct clinical and public health responses. Surgery is offered to individuals with trichiasis and antibiotic mass drug administration and interventions to stimulate facial cleanliness and environmental improvement are designed to reduce infection prevalence and transmission. Together, these interventions comprise the SAFE strategy, which is achieving considerable success. Although much work remains, a continuing public health problem from trachoma in the year 2030 will be difficult for the world to excuse.

EFFECT OF CURCUMIN AS AN ADJUNCT TO SCALING AND ROOT PLANING, AND ITS THERAPEUTIC EFFECT ON SALIVARY NITRIC OXIDE LEVELS IN PATIENTS WITH CHRONIC PERIODONTITIS – A CLINICO – BIOCHEMICAL STUDY

Context (Background): Periodontitis is an infectious inflammatory disease with increase in salivary Nitric oxide levels and Curcumin is known to inhibit inflammatory mediators and neutralize nitric oxide which is expressed in salivary glands. To evaluate and compare the possible improvement in parameters of periodontal disease and salivaryAim: nitric oxide levels in patients undergoing scaling and root planing (SRP) alone and scaling and root planing (SRP) with systemic curcumin administration. In one group, systemic curcumin will be administered along withSettings & Design: SRP & in another group only SRP will be performed. In Group A, SRP along with systemicMethods & Materials: curcumin was administered, and in Group B only SRP was performed. In both the groups, periodontal parameters such as the plaque Index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL), presence or absence of bleeding on probing (BOP) and salivary nitric oxide (NO) levels by spectrophotometer were assessed at baseline and after three month. Chi-Square-test was used so as to evaluate and compare theStatistical Analysis used: possible improvement in parameters of periodontal disease and salivary nitric oxide levels in patients undergoing scaling and root planing (SRP) alone and scaling and root planing (SRP) with systemic curcumin administration. Results & Conclusions: Clinically significant results with improvement in clinical parameters and reduction in salivary NO levels were noticed in both the groups, although test group showed more reduction in the salivary NO levels when compared to the control group thus concluding that administration of systemic curcumin is effective against salivary NO levels and can be used as an adjunct to SRP.

Structures of oxysterol sensor EBI2/GPR183, a key regulator of the immune response

Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular regions of lymphoid tissues through binding the EBI2 (GPR183) to stimulate effective adaptive immunity and antibody production during infection. Aberrant EBI2 signaling is implicated in inflammatory bowel disease, sclerosis, and infectious disease. Here, we report the cryo-EM structures of an EBI2-Gi signaling complex with its endogenous agonist 7α,25-OHC and that of an inactive EBI2 bound to the inverse agonist GSK682753A. These structures reveal an agonist binding site for the oxysterol and a potential ligand entrance site exposed to the lipid bilayer. Mutations within the oxysterol binding site and the Gαi interface attenuate G protein signaling and abolish oxysterol-mediated cell migration indicating that G protein signaling directly involves in the oxysterol-EBI2 pathway. Together, these findings provide new insight into how EBI2 is activated by an oxysterol ligand and will facilitate the development of therapeutic approaches that target EBI2-linked diseases.

First survey on seroprevalence of Japanese encephalitis in long-tailed macaques (Macaca fascicularis) in Bali, Indonesia.

Background and Aim:Japanese encephalitis (JE) is a zoonotic infectious inflammatory brain disease caused by the JE virus (JEV). Considerable research into the seroprevalence of JE in domestic animals has been conducted, but there have been no reports of its occurrence in wild animals, including long-tailed macaques (Macaca fascicularis). This study aimed to estimate the seroprevalence of JEV infection and its determinants in long-tailed macaques in Bali and the prevalence of mosquito vectors.Materials and Methods:Blood samples (3 mL) were collected from a population of M. fascicularis (92 heads) inhabiting a small forest with irrigated rice field nearby (wetland area) in Ubud, Gianyar, and from two populations in dryland areas with no wet rice field (Uluwatu, Badung, and Nusa Penida, Bali Province, Indonesia). The collected sera were tested for antibodies against JEV using a commercially available enzyme-linked immunosorbent assay kit (qualitative monkey JE Immunoglobulin G antibody kit). The seropositivity of the antibodies was then compared based on different variables, namely, habitat type, age, and sex.Results:The seroprevalence of the JEV antibodies in all the samples tested was found to be 41.3%. The seropositivity of the monkey serum samples collected from the wetland area was 46.4%, which was higher than the seropositivity of the sera samples collected from the dried field areas (1.25%). Monkey sera collected from the wetland areas were 6.1 times (odds ratio [OR]: 6.1; 95% confidence interval [CI]: 0.71-51.5, p>0.05) more likely to be seropositive compared to the monkey sera collected from the dried field areas. Meanwhile, female monkeys were 1.79 times (OR: 1.79; 95% CI: 0.76-4.21; p>0.05) more likely to be seropositive to JEV than males. Similarly, juvenile monkeys were 2.38 times (OR: 2.38; 95% CI: 0.98-5.79); p>0.05) more likely to be seropositive against the JEV than adult monkeys. However, none of these differences achieved statistical significance. Regarding the JEV mosquito vector collection, more Culex mosquitoes were found in the samples from the wetland areas than from the dried field areas.Conclusion:The study confirms the existence of JEV infection in long-tailed macaques in Bali. There were patterned seropositivity differences based on habitat, age, and sex of the monkeys, but these were not significant. The possibility of monkeys as a JEV reservoir and the presence of the mosquitoes as the JEV vector are suggested but require more study to confirm.

Abstract 477: The Regulatory Role Of TIFA In The Noncanonical Inflammasome

Noncanonical inflammasome is a novel form of inflammasome, in which caspase-4/5 are both the effectors and the receptors. The activation of the noncanonical inflammasome induces pyroptosis and NLRP3 inflammasome activation. Although intracellular lipopolysaccharide (LPS) is a well-known inducer of noncanonical inflammasome, the role of noncanonical inflammasome in various infectious and noninfectious diseases is still unknown. TIFA [TRAF-interacting protein with a forkhead-associated (FHA) domain] is an immune regulator that activates the NF-κB pathway and the NLRP3 inflammasome and is upregulated in the granulocytes of MIS-C patients. TIFA self-oligomerizes via the interaction between the FHA domain and phosphorylated Thr9 on adjacent TIFA molecules. Phosphorylated TIFA oligomerizes TRAF6 or caspase-1 which ultimately activates NF-κB and the NLRP3 inflammasome. We found that several inflammatory conditions induced the noncanonical inflammasome, the release of IL-1β, and pyroptosis. Mechanistically, TIFA oligomerized caspase-4 and activated caspase-4 via TIFA Thr9 phosphorylation. By analyzing COVID-19 single-cell RNA sequencing dataset, we found that the TIFA/caspase-4 pathway is upregulated in COVID-19-specific neutrophils subset. Leukocytes isolated from COVID-19 patients exhibited activated TIFA and caspase-4 p30, suggesting that the TIFA/caspase-4 pathway played a role during the onset of COVID-19. Together, our results reveal a novel mechanism of the noncanonical inflammasome and its involvement in non-bacterial infectious and sterile inflammatory diseases.

Increased M1 macrophage activity makes females more sensitive to Francisella tularensis infection

Abstract The intensity of the inflammatory response differs between males and females, with females having a stronger basal inflammatory response compared with males. This leads to differences in sensitivity to autoimmune and infectious diseases. Males tend to be more susceptible to infectious diseases whereas females tend to be more susceptible to autoimmune diseases. However, certain infectious diseases cause disease by over stimulating an inflammatory response resulting in dysregulation of cytokine production and generation of a cytokine storm. We hypothesized that the elevated basal inflammatory state of females would make them more susceptible to inflammatory infectious diseases such as Francisella tularensis. Indeed, survival and immunological studies demonstrated that females had a stronger innate immune response and were more likely to succumb to tularemic-disease compared with males. Importantly, this dichotomy was independent of hormonal signaling. We traced the source of this elevated inflammatory response to alterations in the M1 and M2 macrophage activation profile. In females, M1 macrophages were activated earlier than in males in response to inoculation. These M1 macrophages from female mice showed a stronger activation both in vivo and in vitro cultures. This was consistent in both mouse and human systems. Our results demonstrate that females possess a higher abundance of M1 macrophages and that these M1 macrophages are more inflammatory in response to F. tularensis infection. This suggests that the consequence of the dichotomy between the male and female inflammatory response is dependent upon the mechanism of disease triggered by infectious diseases. Supported by grants from the NIH (SC1 GM122699-01A1) and NSF (MRI 1626587).

The emerging oral pathogen, Filifactor alocis, extends the functional lifespan of human neutrophils.

Periodontitis is a chronic inflammatory infectious disease that affects the integrity of tooth‐supporting tissues and has adverse systemic consequences. Advances in sequencing technologies have uncovered organisms that are exclusively found in high numbers in periodontal lesions, such as the gram‐positive anaerobic rod, Filifactor alocis. F. alocis can manipulate neutrophil effector functions, which allows the organism to survive within these granulocytes. Several neutrophil functions have been tested in the context of F. alocis challenge, but the effect of the organism on neutrophil apoptosis is still unknown. RNA sequencing of human neutrophils challenged with F. alocis showed that apoptosis pathways were differentially regulated. Compared to media‐cultured controls, F. alocis‐challenged neutrophils maintain their nuclear morphology, do not stain for Annexin V or 7‐AAD, and have decreased DNA fragmentation. Inhibition of apoptosis by F. alocis involved reduced caspase‐3, −8, and − 9 activation and upregulation of important anti‐apoptotic proteins. Prolonged lifespan was dependent on contact through TLR2/6, and F. alocis‐challenged neutrophils retained their functional capacity to induce inflammation for longer timepoints. This is the first in‐depth characterization of neutrophil apoptotic programs in response to an oral pathogen and provides key information on how bacteria manipulate immune cell mechanisms to maintain a dysregulated inflammatory response.

Association of Helicobacter pylori infection with chronic obstructive pulmonary disease

Introduction: Chronic obstructive pulmonary disease (COPD) is a disease that is systematically characterized by an abnormal inflammatory response affecting the airways, interstitium and vascular bed through reactions to gas and particles, especially cigarette smoking. Recent studies have shown an association between Helicobacter pylori infection and various inflammatory diseases. H. pylori is a gram-negative, microbial bacterium that can be resistant to acidic stomach conditions and can interfere with gastric urease production. In this study, we examined the relationship between H. pylori infection in patients with COPD and the prevalence of H. pylori infection. Objectives: Determining the association between H. pylori infection and COPD. Patients and Methods: This case-control study is based on the Persian cohort study of patients who were referred to the digestive disease research center after being identified in the pulmonary clinic for H. pylori fecal antigen. Information on demographic variables and other related variables were obtained. Finally, the collected information was entered into SPSS software version 24 and the results were displayed descriptively using distribution and frequency tables and graphs and analytical statistics were analyzed using t test and logistic regression. Results: Out of 250 patients, 134 (53.6%) tested positive for H. pylori and 116 (46.4%) tested negative. Out of a total of 250 non-infected people; 106 patients (42.4%) were positive and 144 patients (57.6%) were negative. The two groups were statistically significantly different based on the chi-square test (P = 0.012). Conclusion: Our study showed a direct and significant relationship between H. pylori and COPD, which can be due to the effect of bacteria on lung growth in early life and also the development of systemic inflammation throughout life.

Protocolo diagnóstico del paciente con exantema y fiebre

The differential diagnosis of exanthem and fever in adults is extensive. A large part of conditions that include them are benign, although there are some severe diseases that require a rapid diagnosis and treatment. Evaluating the characteristics of the exanthem, its distribution, and its progress over time is fundamental. The habitual forms of presentation tend to be maculopapules, vesicles, blisters, petechia, or nodules. The etiology varies widely and within each category are infectious causes, inflammatory diseases, and drug hypersensitivity reactions.

Heterogeneity of type 2 innate lymphoid cells.

More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a first line of defence against infections before the recruitment of adaptive immune cells. Initially, ILC2s were implicated in the early immune response to parasitic infections, but it is now clear that ILC2s are highly diverse and have crucial roles in the regulation of tissue homeostasis and repair. ILC2s can also regulate the functions of other type 2 immune cells, including T helper 2 cells, type 2 macrophages and eosinophils. Dysregulation of ILC2s contributes to type 2-mediated pathology in a wide variety of diseases, potentially making ILC2s attractive targets for therapeutic interventions. In this Review, we focus on the spectrum of ILC2 phenotypes that have been described across different tissues and disease states with an emphasis on human ILC2s. We discuss recent insights in ILC2 biology and suggest how this knowledge might be used for novel disease treatments and improved human health.

İnce bağırsakta kitle oluşturarak ileus ile kendini gösteren AA amiloidoz

Introduction:
 Intestinal amyloidosis frequently encountered as a part of systemic amyloidosis, but rarely can be confined in the gastrointestinal tract.
 Case report:
 A 54-year-old male presented with the complaint of gas and stool discharge. Urgently segmental bowel resection was performed for ileus. Macroscopically nodular lesions, the largest at 7x3x0.7 cm in size were observed in the intestinal lumen. Microscopically; the accumulation of dense eosinophilic material that formed a mass in the submucosal area was noted. This material was positive with Crystal Violet, Congo Red and Amyloid A. Kappa and Lambda were negative. 
 No monoclonal gammopathy, increase in serum amyloid A levels, chronic inflammatory disease, infectious disease or malignancy was determined. The case was evaluated as "intestinal AA amyloidosis".
 Discussion:
 While AA amyloidosis was existent in our case, it comprised a mass lesion and caused intestinal obstruction. It is also exraordinary for AA amyloidosis to be confined in gastrointestinal tract.

Vascular Permeability in Diseases.

Vascular permeability is a selective mechanism that maintains the exchange between vessels, tissues, and organs. The regulation was mostly studied during the nineteenth century by physiologists who defined physical laws and equations, taking blood, tissue interstitial, and oncotic pressure into account. During the last decades, a better knowledge of vascular cell functions and blood-vessel interactions opens a new area of vascular biology. Endothelial cell receptors vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule (ICAM), vascular endothelial growth factor receptor (VEGFR-2), receptor for advanced glycation end products (RAGE), and mediators were identified and their role in homeostasis and pathological situations was described. The molecular differences of endothelial cell junctions (tight, gap, and adherens junctions) and their role in vascular permeability were characterized in different organs. The main mediators of vasomotricity and permeability, such as prostaglandins, nitric oxide (NO), prostacyclin, vascular growth factor (VEGF), and cytokines, have been demonstrated to possess major functions in steady state and pathological situations. Leukocytes were shown to adhere to endothelium and migrate during inflammatory situations and infectious diseases. Increased vascular permeability is linked to endothelium integrity. Glycocalyx, when intact, may limit cancer cell metastasis. Biological modifications of blood and tissue constituents occurring in diabetes mellitus were responsible for increased permeability and, consequently, ocular and renal complications. Vascular pressure and fluidity are major determinants of pulmonary and cerebral edema. Beside the treatment of the infectious disease, of the blood circulation dysfunction and inflammatory condition, drugs (cyclooxygenase inhibitors) and specific antibodies anti-cytokine (anti-VEGF) have been demonstrated to reduce the severity and the mortality in diseases that exhibited enhanced vascular permeability.

Study of hypoalbuminemia in paediatric intensive care unit admitted children

Background: Albumin has several important properties in both health and disease. Hypoalbuminemia has been considered as an indicator of disease severity and mortality in adult patients, but its role in pediatric patients is not well established. Study aimed to understand importance of hypoalbuminemia in critical illness in paediatric patients.Methods: This was a cross-sectional study conducted amongst children aged 2 months to 18 years admitted at PICU of a tertiary care hospital over a period of 6 months. Study protocol was approved by institutional ethical committee.Results: Amongst the total studied cases (110), 59 cases of the total contributed to hypoalbuminemia. According to primary system affected, post COVID MISC, acute infectious diseases, systemic inflammatory disease and sepsis are some of the common conditions associated with higher incidence of hypoalbuminemia. Statistically significant difference was found in this group of population. Amongst the hypo-albuminemic group 59 (53.64%), in mild category there were 42 (38.18%) patients and in severe category there were 17 patients (15.46%).Conclusions: Hypoalbuminemia is common in patients admitted to the PICU. Post COVID MISC, acute infectious diseases, sepsis and systemic inflammatory diseases are most common conditions associated with it. Hypo-albuminemiais an important indicator of mortality in PICU and serum albumin is a good and reliable indicator for detecting mortality.