Plasma Exudation Research Articles

Well-controlled mucosal exudation of plasma proteins in airways with intact and regenerating epithelium.

Superficial, systemic microcirculations, distinct from the pulmonary circulation, supply the mucosae of human nasal and conducting airways. Non-injurious, inflammatory challenges of the airway mucosa cause extravasation without overt mucosal oedema. Instead, likely reflecting minimal increases in basolateral hydrostatic pressure, circulating proteins/peptides of all sizes are transmitted paracellularly across the juxtaposed epithelial barrier. Thus, small volumes of extravasated, unfiltered bulk plasma appear on the mucosal surface at nasal and bronchial sites of challenge. Importantly, the plasma-exuding mucosa maintains barrier integrity against penetrability of inhaled molecules. Thus, one-way epithelial penetrability, strict localization, and well-controlled magnitude and duration are basic characteristics of the plasma exudation response in human intact airways. Invivo experiments in human-like airways demonstrate that local plasma exudation is also induced by non-sanguineous removal of epithelium over an intact basement membrane. This humoral response results in a protective, repair-promoting barrier kept together by a fibrin-fibronectin net. Plasma exudation stops once the provisional barrier is substituted by a new cellular cover consisting of speedily migrating repair cells, which may emanate from all types of epithelial cells bordering the denuded patch. Exuded plasma on the surface of human airways reflects physiological microvascular-epithelial cooperation in first line mucosal defense at sites of intact and regenerating epithelium.

Impact of Isolated Exercise-Induced Small Airway Dysfunction on Exercise Performance in Professional Male Cyclists.

Professional cycling puts significant demands on the respiratory system. Exercise-induced bronchoconstriction (EIB) is a common problem in professional athletes. Small airways may be affected in isolation or in combination with a reduction in forced expiratory volume at the first second (FEV1). This study aimed to investigate isolated exercise-induced small airway dysfunction (SAD) in professional cyclists and assess the impact of this phenomenon on exercise capacity in this population. This research was conducted on professional cyclists with no history of asthma or atopy. Anthropometric characteristics were recorded, the training age was determined, and spirometry and specific markers, such as fractional exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), were measured for all participants. All of the cyclists underwent cardiopulmonary exercise testing (CPET) followed by spirometry. Compared with the controls, 1-FEV3/FVC (the fraction of the FVC that was not expired during the first 3 s of the FVC) was greater in athletes with EIB, but also in those with isolated exercise-induced SAD. The exercise capacity was lower in cyclists with isolated exercise-induced SAD than in the controls, but was similar to that in cyclists with EIB. This phenomenon appeared to be associated with a worse ventilatory reserve (VE/MVV%). According to our data, it appears that professional cyclists may experience no beneficial impacts on their respiratory system. Strenuous endurance exercise can induce airway injury, which is followed by a restorative process. The repeated cycle of injury and repair can trigger the release of pro-inflammatory mediators, the disruption of the airway epithelial barrier, and plasma exudation, which gradually give rise to airway hyper-responsiveness, exercise-induced bronchoconstriction, intrabronchial inflammation, peribronchial fibrosis, and respiratory symptoms. The small airways may be affected in isolation or in combination with a reduction in FEV1. Cyclists with isolated exercise-induced SAD had lower exercise capacity than those in the control group.

Perilipin 2-positive mononuclear phagocytes accumulate in the diabetic retina and promote PPARγ-dependent vasodegeneration.

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia, leads to nonproliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retina barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels, and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation remains unknown. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas expressed perilipin 2 (PLIN2), a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from patients with T2DM or with palmitate concentrations typical of those found in T2DM plasma, but not under high-glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induced capillary degeneration in ex vivo explants that was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study reveals a mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target for inhibition of lipid-activated MPs in DR.

Proteomic Profiling of Extracellular Vesicles Isolated from Plasma and Peritoneal Exudate in Mice Induced by Crotalus scutulatus scutulatus Crude Venom and Its Purified Cysteine-Rich Secretory Protein (Css-CRiSP).

Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in different diseases. This study aimed to identify proteins in peritoneal exudate and plasma EVs isolated from BALB/c mice following a 30 min post-injection of Crotalus scutulatus scutulatus venom and its purified CRiSP (Css-CRiSP). EVs were isolated from these biofluids using the EVtrap method. Proteomic analysis of exudate- and plasma-derived EVs was performed using LC-MS/MS. We observed significant upregulation or downregulation of proteins involved in cell adhesion, cytoskeleton rearrangement, signal transduction, immune responses, and vesicle-mediated transports. These findings suggest that svCRiSPs play a crucial role in the acute effects of venom and contribute to the local and systemic toxicity of snakebites.

Abstract 2103: Immunophenotyping of extracellular vesicles isolated from lymphatic exudate identifies CD24 as a marker for lymph node metastases in oral cavity squamous cell carcinoma

Abstract Background: Squamous cell carcinoma of the oral cavity (OSCC) is debilitating and fatal with a high risk of lymph node metastases. One of the key problems is that currently there is no robust molecular biomarker to determine whether the tumor has spread or is at risk of spreading to the regional lymph nodes, the first echelon that OSCC spreads to. Extracellular vesicles (EVs) are functional nanoparticles that are bound by natural protein-lipid bilayers. They are deliberately packaged and proactively secreted by all types of cells and serve as intercellular communication vehicles. Tumors release an excess of EVs which are loaded with the molecular and genetic cargo of the parental tumor cells. Methods: Following ethical approval and written informed consent, pre-surgical plasma as well as matched post-surgical lymphatic drainage fluid were collected from 20 OSCC patients (nodal disease n=6, no node n=14), and control plasma was also collected from healthy donors. EVs were isolated by ultracentrifugation, quantified and characterized by nanoparticle tracking analysis, transmission electron microscopy, and western blot. Immune profiling of 37 EV surface markers was determined using flow cytometry with the MACSPlex Exosome kit. Results: Lymphatic exudate was greatly enriched in EVs in comparison to plasma. Common EV tetraspanins, platelet markers, cancer-related proteins, as well as characteristic markers of immune cells were detected in both plasma and lymphatic exudate EVs based on normalized median fluorescence intensity (nMFI). The presence of OSCC led to an altered composition of blood cell-derived EVs. Elevated levels of CD3, CD25, and CD86, and cancer stem cell marker CD133 were observed in the plasma EVs. However, there were no significant changes in EV markers in plasma between patients with and without lymph node metastasis. Notably, EVs isolated from plasma and lymphatic exudate revealed completely divergent signatures of EV surface markers. Among them, cancer-related protein CD24 was found to be the most highly expressed EV marker in lymphatic exudate from patients with nodal disease (nMFI 1.28±0.50 versus 0.84±0.32, p<0.05) and likewise correlated with advanced disease stages (nMFI 1.17±0.40 versus 0.70±0.27, p<0.05). Conclusions: Plasma-derived EVs are promising non-invasive biomarkers for cancer detection. This study shows that lymphatic exudate is a better source of EV biomarkers due to its high abundance of tumor-related factors directly from draining lymph nodes. In addition, CD24, as reported, is indicative of an immunosuppressive tumor microenvironment and it may serve as a predictor for lymph node metastases and progression of OSCC. These findings shed new light on the understanding of OSCC metastases and provide impetus for consideration of CD24-based liquid biopsy testing and possibly novel immunotherapy. Citation Format: Xinyu Qu, Leanne Lee Leung, Cherrie Wing Kei Ng, Hiu Ching Chan, Zigui Chen, Katie Meehan, Xianhai Zeng, Jason Ying Kuen Chan. Immunophenotyping of extracellular vesicles isolated from lymphatic exudate identifies CD24 as a marker for lymph node metastases in oral cavity squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2103.

Assessment of antibodies in the upper and lower human respiratory tract at steady state and after respiratory viral infection.

There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings. We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were determined in BAL and plasma to assess plasma exudation. IgG and IgA were readily detectable in BAL and NP swabs, albeit at different ratios, while IgM levels were low. The total amount of antibody recovered from NP swabs varied greatly between study participants. Accordingly, the levels of influenza HA-specific antibodies varied, and individuals with lower amounts of total Ig in NP swabs had undetectable levels of HA-specific Ig. Similarly, the total amount of antibody recovered from BAL varied between study participants. However, severely ill patients showed evidence of increased plasma exudation, which may confound analysis of their BAL samples for mucosal antibodies. Nasopharyngeal swabs collected for diagnostic purposes may have utility in assessing antibodies from the human nasal mucosa, but variability in sampling should be accounted for. BAL samples can be utilised to study antibodies from the lower respiratory tract, but the possibility of plasma exudation should be excluded.

The Extent of Burn Injury Significantly Affects Serum Micro- and Macroelement Concentrations in Patients on the First Day of Hospitalisation.

Burns exceeding 30% of total body surface area (TBSA) result in considerable hypovolemia coupled with the formation and release of inflammatory mediators, leading to subsequent systemic effects known as burn shock. Because of plasma exudation and the associated losses of large quantities of minerals, severe burns can lead to nutritional deficiencies and consequently disrupt homeostasis and metabolism of the entire body. The study group comprised 62 patients, who were divided into 3 groups according to the severity of burns. Serum samples were tested for concentrations of Ca, Mg, Mn, P, K, Zn, Cu, Fe, Se, Na, Cr, Ni, and Al. The mineral concentrations in serum of patients with burn injuries differ significantly from reference values, but this is not affected by the extent of the body burn. There are statistically significant decreases in serum concentrations of elements important for antioxidant protection (Zn, Cu, Se), and significant increases in the concentrations of toxic elements (Al and Ni), which may aggravate the effects associated with the state of burn shock. The Spearman rank correlation analysis did not reveal any statistically significant relationships between the serum concentrations of Mn, Ni, Al, K, Na, P, Mg, Zn, Se, Cr and the affected body surface area and severity of the burn—the values were at the lower end of the reference range. The obtained results indicate that proper nutrition, including elements replenishment, is extremely important in the recovery process of burn patients and time to nutrition is an important factor affecting patient survival after severe burn.

Therapeutic Effect of <i>Aloe vera</i> on Croton Oil Induced Hemorrhoids

Hemorrhoids are vascular structures in the anal canal with swollen veins in the lowest part of the rectum/anus. Till date, there is no specific treatment available for different grades of hemorrhoids. However, it is evident that lesser invasive options are to have opted for at the earliest along with conservative measures such as analgesics and anti-inflammatory agents. The study evaluates the efficacy of gel obtained from Aloe barbadensis Miller in treating hemorrhoids in a croton oil-induced Wistar rat model. Animals were allocated into 5 groups. Group I and II served as the normal and negative control, Group III as standard, and Group IV and V received an oral route and a topical route respectively. Biochemical parameters such as TNF-? and IL-6 were estimated in each group after the therapy of 5 days. Quantitative estimation of edema was done by determining the Evans blue dye concentration in the plasma exudates in recto-anal tissue. The recto-anal coefficient was estimated as a direct measure of inflammation. Histopathological variations among the groups were analyzed. Statistical analysis of the data affirms the curative effect of aloe vera on Hemorrhoids. Results demonstrate that aloe gel is much more effective when compared to Pilex ointment which was used as standard (p<0.05). However, oral preparation was not found to be effective in mitigating the disease as that standard (p>0.05).

Insights from Transcriptomics: CD163+ Profibrotic Lung Macrophages in COVID-19.

Coronavirus disease (COVID-19) begins with upper airway symptoms but proceeds in a significant proportion of patients to life-threatening infection of the lower respiratory tract, where an exuberant inflammatory response, edema, and adverse parenchymal remodeling impair gas exchange. Respiratory failure is caused initially by flooding of the airspaces with plasma exudate, sloughed epithelium, and inflammatory cells. For many patients with COVID-19, this acute phase has been observed to give way to a prolonged course of acute respiratory distress syndrome, and a significant proportion of patients go on to develop fibroproliferative remodeling of the lung parenchyma, which lengthens the duration of respiratory impairment and mechanical ventilation. Monocyte-derived macrophages have previously been implicated in the fibrotic phase of lung injury in multiple models. From several recent studies that used single-cell genomic techniques, a profile of the transcriptomic state of COVID-19 lung macrophages has emerged. Linkages have been made between these macrophages, which are monocyte-derived and CD163+, and profibrotic macrophages found in other contexts, including animal models of fibrosis and idiopathic pulmonary fibrosis. Here, emerging concepts of macrophage profibrotic function in COVID-19 are highlighted with a focus on gaps in knowledge to be addressed by future research.

Case report of sclerosing encapsulating peritonitis secondary to tuberculosis

Sclerosing encapsulating peritonitis (SEP) is a visceral encapsulation syndrome of inflammatory origin, seen as an infrequent cause of intestinal obstruction in young patients. It is a condition characterised by complete encapsulation of small bowel loops by a fibrocollagenous membrane, leading to cocoon formation. Histologically, the membrane is composed mainly of organised fibrin, probably derived from the plasma exudation of peritoneal microvasculature. Clinical presentation is related to the development of altered gut motility, resulting in abdominal pain and features of intestinal obstruction. We here discussed about a young patient who presented with features of intestinal obstruction and diagnosed with SEP, secondary to abdominal tuberculosis and was then treated surgically. SEP as a cause of intestinal obstruction is a rare life threatening entity encountered in day to day practice. Definitive diagnosis of this condition is challenging in the pre-operative period and is usually missed and a high index of suspicion is required.

Pathomorphological sequence of nephron loss in diabetic nephropathy.

Following our previous reports on mesangial sclerosis and vascular proliferation in diabetic nephropathy (DN) (Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ. Am J Physiol Renal Physiol 312: F1101-F1111, 2017; Löwen J, Gröne E, Gröne HJ, Kriz W. Am J Physiol Renal Physiol 317: F399-F410, 2019), we now describe the advanced stages of DN terminating in glomerular obsolescence and tubulointerstitial fibrosis based on a total of 918 biopsies. The structural aberrations emerged from two defects: 1) increased synthesis of glomerular basement membrane (GBM) components by podocytes and endothelial cells leading to an accumulation of GBM material in the mesangium and 2) a defect of glomerular vessels consisting of increased leakiness and an increased propensity to proliferate. Both defects may lead to glomerular degeneration. The progressing compaction of accumulated worn-out GBM material together with the retraction of podocytes out of the tuft and the collapse and hyalinosis of capillaries results in a shrunken tuft that fuses with Bowman's capsule (BC) to glomerular sclerosis. The most frequent pathway to glomerular decay starts with local tuft expansions that result in contacts of structurally intact podocytes to the parietal epithelium initiating the formation of tuft adhesions, which include the penetration of glomerular capillaries into BC. Exudation of plasma from such capillaries into the space between the parietal epithelium and its basement membrane causes the formation of insudative fluid accumulations within BC spreading around the glomerular circumference and, via the glomerulotubular junction, onto the tubule. Degeneration of the corresponding tubule develops secondarily to the glomerular damage, either due to cessation of filtration in cases of global sclerosis or due to encroachment of the insudative spaces. The degenerating tubules induce the proliferation of myofibroblasts resulting in interstitial fibrosis.NEW & NOTEWORTHY Based on analysis of 918 human biopsies, essential derangement in diabetic nephropathy consists of accumulation of worn-out glomerular basement membrane in the mesangium that may advance to global sclerosis. The most frequent pathway to nephron dropout starts with the penetration of glomerular capillaries into Bowman's capsule (BC), delivering an exudate into BC that spreads around the entire glomerular circumference and via the glomerulotubular junction onto the tubule, resulting in glomerular sclerosis and chronic tubulointerstitial damage.

Severity of neurological signs in feline hypertensive encephalopathy may be reflected through brain histopathological lesions

AbstractHypertensive encephalopathy (HE) was diagnosed in two aged cats with chronic kidney disease. The cause for admission was generalised epileptic seizures, with severe, interictal neurological dysfunction (dementia, locomotor dysfunction, cranial nerve deficits). Both cats had systolic hypertension (SH) (180‐220 mm Hg), bilateral retinal detachment, non‐regenerative anaemia and moderate renal azotaemia. Both cats died. Gross lesions were apparent in one cat consisting of white matter oedema in the parietal and temporal lobe and a focal area of malacia. Histopathological examination of brain tissue revealed bilateral severe oedema and astrocytic gliosis in the corona radiata, basal nuclei, thalamus and piriform lobe of both cats. Extensive hyaline and hyperplastic arteriolosclerosis, perivascular plasma exudation and haemorrhages were present throughout the meninges and neuroparenchyma. Histopathological findings reflected the severity of neurological deficits. This could indicate that the severity of the brain lesions is associated with the neurological manifestations of HE.

C-reactive Protein Levels in Plasma and Chronic Venous Ulcer Exudate of Persons Who Inject Drugs: A Pilot Study

Persons who inject drugs (PWID) in the groin, legs, and/or feet are at high risk for chronic venous ulcers (CVUs). The plasma C-reactive protein (CRP) level is a marker of systemic inflammation. This pilot study examined CRP levels in plasma and CVU exudate of PWID. The aims were to (1) compare levels of CRP in plasma and exudate; (2) examine if the CRP level in exudate changed over 4 weeks with wound treatment; and (3) examine the relationship of the exudate CRP level with CVU area, CVU age, number of CVUs, and number of comorbidities. Persons who inject drugs seeking wound care were enrolled in this Institutional Review Board approved prospective, longitudinal, descriptive study. A blood sample was collected on the first visit (week 1); the plasma was then separated. Wound exudate was collected on swabs during the first visit (week 1) and 4 weeks later (week 4). All samples were stored at -80° C. Samples were eluted from swabs using mass spectrometry grade water then aliquoted for CRP analysis. The participants of the study included 14 PWID (mean age, 62.14 ± 4.52 years; mean number of comorbidities, 5.71 ± 1.90; and mean number of ulcers 2.07 ± 1.07 that were present for a mean of 7.96 ± 11.91 years without healing). C-reactive protein level in plasma was a mean of 6.47 ± 8.56 mg/L, with lower levels found in wound exudate but highly correlated (rho = .925). Exudate CRP levels decreased from week 1 to week 4, and the 2 were highly correlated (rho = .895). Exudate CRP level week 1 was not significantly related to wound area, wound age, number of ulcers, or number of comorbidities. Plasma and exudate CRP levels were highly correlated. Exudate CRP levels decreased across time. Future large-scale wound healing studies should examine CRP levels over a longer duration and as they correlate to wound healing.

Early humoral defence: Contributing to confining COVID-19 to conducting airways?

Early airway responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection are of interest since they could decide whether coronavirus disease‐19 (COVID‐19) will proceed to life‐threatening pulmonary disease stages. Here I discuss endothelial‐epithelial co‐operative in vivo responses producing first‐line, humoral innate defence opportunities in human airways. The pseudostratified epithelium of human nasal and tracheobronchial airways are prime sites of exposure and infection by SARS‐CoV‐2. Just beneath the epithelium runs a profuse systemic microcirculation. Its post‐capillary venules respond conspicuously to mucosal challenges with autacoids, allergens and microbes, and to mere loss of epithelium. By active venular endothelial gap formation, followed by transient yielding of epithelial junctions, non‐sieved plasma macromolecules move from the microcirculation to the mucosal surface. Hence, plasma‐derived protein cascade systems and antimicrobial peptides would have opportunity to operate jointly on an unperturbed mucosal lining. Similarly, a plasma‐derived, dynamic gel protects sites of epithelial sloughing‐regeneration. Precision for this indiscriminate humoral molecular response lies in restricted location and well‐regulated duration of plasma exudation. Importantly, the endothelial responsiveness of the airway microcirculation differs distinctly from the relatively non‐responsive, low‐pressure pulmonary microcirculation that non‐specifically, almost irreversibly, leaks plasma in life‐threatening COVID‐19. Observations in humans of infections with rhinovirus, coronavirus 229E, and influenza A and B support a general but individually variable early occurrence of plasma exudation in human infected nasal and tracheobronchial airways. Investigations are warranted to elucidate roles of host‐ and drug‐induced airway plasma exudation in restriction of viral infection and, specifically, whether it contributes to variable disease responses following exposure to SARS‐CoV‐2.

The Local Alternative Ti-6Al-4V Alloy Coating of Surgery Steel Instruments for Laser Deposition Forming

Aiming at the medical practice problems of the surgical steel medical instruments, such as the crevice corrosion, the poor mechanical compatibility and the Ni, Cr plasma exudation, the laser deposition of Ti-6Al-4V alloy cladding layer at the local functional area as alternative coating was proposed and realized as a new process method. The accurate element content and good formability Ti-6Al-4V cladding powder was chosen, the low power and high duty cycle optimized laser process was adopt, the alternative coating of good fusion and low dilution was prepared. Through the elemental line scanning, the interface microstructure analysis and the experiments of basic mechanical properties, the basic properties of the cladding were characterized and verified. The experiments results showed that, the Ti, Al and V contents of the top coating were respectively about 88%, 4.9% and 3.9%, no sensitizing ions such as Cr and Ni were detected. Initial equiaxed α phase, flake β phase dist were distributed in the coating and interface, the α' martensite was precipitated at the boundary of the flake β phase, some refined granular β phase dispersion pinned to the grain boundary of basket structure. The microhardness of cladding layer was 352.08~312.76 HV0.1. The friction coefficient of the cladding layer was about 0.22~0.65. A new technology and method reference for improving and upgrading the performance of surgical medical devices is provided by this research.

Zinc Supplementation: Immune Balance of Pregnancy During the Chronic Phase of the Chagas Disease

Chagas disease or American trypanosomiasis is caused by the protozoan Trypanosoma cruzi and is endemic of the Americas. The control of the disease is restricted to toxic and potentially teratogenic drugs, which limit the use during pregnancy. The use of food supplementation offers a safe and low-cost form to alleviate Chagas disease symptoms, mostly in areas with alimentary risk. For example, zinc demonstrates positive effects in immune response, including in Chagas disease during pregnancy. This study describes the innate response in pregnant rats chronically infected with T. cruzi and supplemented with zinc. Pregnant female Wistar rats, infected with T. cruzi, were treated with 20mg/kg/day zinc sulfate and euthanized on the 18th day. Samples (plasma, splenocytes, and peritoneal exudate) were collected and several immune parameters (nitric oxide, RT1B, CD80/CD86, MCP-1, CD11b/c, NK/NKT, IL-2, IL-10, INF-cc, and apoptosis) evaluated. Under Zinc supplementation and/or T. cruzi infection, the gestation developed normally. Several innate immune parameters such as RT1B, CD80/CD86, MCP-1 expressing lymphocytes, IL-2, and IL-17 were positively altered, whereas nitric oxide, CD11b/c, NK/NKT, apoptosis, INF-γ, and corticosterone demonstrated a pro-pregnancy pattern. Our results indicated that zinc has diverse effects on immune response during pregnancy. An anti-T. cruzi immunity, as well as a pro-gestation response, were observed after zinc supplementation. The complete comprehension of zinc supplementation in pregnancy will base an adequate strategy to alleviate Chagas disease symptoms and propagation, especially for populations from endemic areas.

Затрудненное носовое дыхание в практике оториноларинголога: чем помочь?

The article discusses the most common causes of diseases that cause difficulty in nasal breathing. According to the analysis of medical documentation, diseases accompanied by nasal obstruction and rhinorrhea are the most common human diseases. The priority role in the development of the clinical symptoms of rhinitis is played by the release of inflammatory mediators – histamine and bradykinin. Histamine in rhinitis mediates a cascade of pathological reactions, as a result of which local vasodilation develops, accompanied by swelling of the mucous membranes; nasal congestion; increased permeability of the vascular wall; exudation of blood plasma; irritation of nerve endings; triggering reflex mechanisms by stimulating trigeminal histamine receptors. Peculiarities of the course of intermittent and persistent forms of allergic rhinitis, the pathogenesis of allergic inflammation are considered. To reliably eliminate abundant rhinorrhea, combined with nasal congestion, the authors recommend the use of a combined nasal spray, which contains phenylephrine and cetirizine (Phenylephrine + Cetirizine). Based on the analysis of literature data, the effectiveness and safety of the use of the topical form of cetirizine are substantiated. Aspects of the clinical use of the combination of phenylephrine and cetirizine in inflammatory and allergic diseases of the nasal cavity and paranasal sinuses, in the pathogenesis of which the key role is played by swelling of the mucous membrane of the nasal cavity, are examined. It is proved that the new combined nasal spray of domestic production is an effective and safe method for treating patients with manifestations of various forms of rhinitis and nasal obstruction.

PS1290 HEPARIN‐ANALOGUE SEVUPARIN INHIBITS STREPTOCOCCUS‐INDUCED VASCULAR HYPERPERMEABILITY THROUGH NEUTRALIZING NEUTROPHIL‐DERIVED PROTEINS

Background:Acute lung injury (ALI) and respiratory distress can develop as a consequence of sepsis with pathogens such as Group A streptococcus (GAS) including S. pyogenes. In the pathogenesis of sepsis‐associated ALI, plasma exudation and leukocyte accumulation in the lungs are central events, and endothelial barrier disruption brought on by degranulation of neutrophil‐derived proteins is considered a causative factor. Heparin and heparin derivatives have been suggested as novel therapeutics in sepsis on the basis of their pleiotropic anti‐inflammatory effects.Aims:Here, we study wheter sevuparin, a heparinoid wihich lacks anticoagulant activity, affects neutrophil‐induced lung plasma leakage.Methods:A murine model of systemic inflammation evoked by heat‐killed GAS and furthermore, we utilized human neutrophils and endothelial cell monolayersResults:We demonstrate that sevuparin inhibits hkGAS‐induced endothelial barrier disruption by neutralizing the activity of neutrophil‐derived proteins. By mass spectrometry of neutrophil secretion we identify candidate proteins, including serprocidins, S100 proteins and histone H4, that interact with sevuparin and that are responsible for the disruptive effect on endothelial integrity.Summary/Conclusion:Collectively, our results corroborate the role of neutrophil‐derived proteins in vascular hyperpermeability caused by Group A streptococci, and suggest sevuparin as a potential therapeutic in acute neutrophilic inflammation.

Hypothesis regarding the effects of gonadotropins on the level of free fatty acids and phospholipids in serum and follicular fluid during controlled ovarian stimulation

Controlled ovarian stimulation (COS) is used to augment the number of retrieved oocytes in in vitro fertilization (IVF). Follicular fluid (FF) contributes significantly to oocyte quality. Since the FF is composed of follicular secretions and plasma exudation, it reflects alterations in granulosa and thecal cells secretion as well as changes in the level of plasma constituents. Phospholipids (PL) and free fatty acids (FFA) are important constituents of both, FF and serum. Our hypothesis is that COS affects the level of PL and FFA in serum. Furthermore, since the level of PL and FFA in FF partially depends on their levels in serum, as a collaterally of our hypothesis is that the existing level of PL and FFA in serum correlates with the levels of PL and FFA in FF, and that the dose of applied gonadotropins during COS will correlate with the levels of PL and FFA in serum and FF. In addition, we assume that the level of PL and FFA in serum and in FF after COS will correlate with the retrieved number of GQ oocytes, one of the most important outcomes of COS..

Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier in acute inflammation.

Neutrophil recruitment and plasma exudation are key elements in the immune response to injury or infection. Activated neutrophils stimulate opening of the endothelial barrier; however, the underlying mechanisms have remained largely unknown. In this study, we identified a pivotal role of the proinflammatory kallikrein-kinin system and consequent formation of bradykinin in neutrophil-evoked vascular leak. In mouse and hamster models of acute inflammation, inhibitors of bradykinin generation, and signaling markedly reduced plasma exudation in response to chemoattractant activation of neutrophils. The neutrophil-driven leak was likewise suppressed in mice deficient in either the bradykinin B2 receptor or factor XII (initiator of the kallikrein-kinin system). In human endothelial cell monolayers, material secreted from activated neutrophils induced cytoskeletal rearrangement, leading to paracellular gap formation in a bradykinin-dependent manner. As a mechanistic basis, we found that a neutrophil-derived heparin-binding protein (HBP/azurocidin) displaced the bradykinin precursor high-molecular-weight kininogen from endothelial cells, thereby enabling proteolytic processing of kininogen into bradykinin by neutrophil and plasma proteases. These data provide novel insight into the signaling pathway by which neutrophils open up the endothelial barrier and identify the kallikrein-kinin system as a target for therapeutic interventions in acute inflammatory reactions.-Kenne, E., Rasmuson, J., Renné, T., Vieira, M. L., Müller-Esterl, W., Herwald, H., Lindbom, L. Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier in acute inflammation.