Ultrafiltrate Of Plasma Research Articles

Sexual dimorphism in renal metabolism, hemodynamics and diseases

Age-related decline of renal function is faster in males than in age-matched females, manifesting in increased susceptibility to both chronic and acute kidney diseases among males. In the mouse kidney, sexually dimorphic gene activity maps predominantly to proximal tubule (PT) segments, where most reabsorption of water and salt happens, with a high energetic demand. Recent work suggests that male PTs undergo excessive oxidative stress to meet the high energetic demand, while female PTs exhibit an anti-oxidation state. However, it remains elusive how the observed molecular differences relate to sex disparities in renal physiology and pathophysiology. Glomerular filtration rate (GFR) is tightly regulated by tubuloglomerular feedback (TGF) within renal tubules to optimize ultrafiltration of plasma and reabsorption of essential molecules. Importantly, GFR shows a sustained oscillatory pattern over time in rodents, and loss of GFR oscillations is associated with cessation of reabsorption activities and with the occurrence of ischemia-reperfusion injuries in the kidney, as well as with systemic hypertension. To study the relationship between intracellular metabolic events and renal physiology, we developed a mathematical model of TGF linking metabolic regulation within PT cells to fluid handling and salt reabsorption in the nephron, using renal blood flow and intra-vital imaging data. Analysis of this model revealed that dynamical properties of the system differ between male and female kidneys, resulting in male kidneys being more prone to stress-induced damage, thus building towards an explanation for sexual dimorphism in renal aging and diseases. With this mechanistic model, our work also provides insight into how pharmacological interventions can be employed to confer renoprotection. The authors received no funding for this study. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Advances in Non-Electrochemical Sensing of Human Sweat Biomarkers: From Sweat Sampling to Signal Reading.

Sweat, commonly referred to as the ultrafiltrate of blood plasma, is an essential physiological fluid in the human body. It contains a wide range of metabolites, electrolytes, and other biologically significant markers that are closely linked to human health. Compared to other bodily fluids, such as blood, sweat offers distinct advantages in terms of ease of collection and non-invasive detection. In recent years, considerable attention has been focused on wearable sweat sensors due to their potential for continuous monitoring of biomarkers. Electrochemical methods have been extensively used for in situ sweat biomarker analysis, as thoroughly reviewed by various researchers. This comprehensive review aims to provide an overview of recent advances in non-electrochemical methods for analyzing sweat, including colorimetric methods, fluorescence techniques, surface-enhanced Raman spectroscopy, and more. The review covers multiple aspects of non-electrochemical sweat analysis, encompassing sweat sampling methodologies, detection techniques, signal processing, and diverse applications. Furthermore, it highlights the current bottlenecks and challenges faced by non-electrochemical sensors, such as limitations and interference issues. Finally, the review concludes by offering insights into the prospects for non-electrochemical sensing technologies. By providing a valuable reference and inspiring researchers engaged in the field of sweat sensor development, this paper aspires to foster the creation of innovative and practical advancements in this domain.

Hemostatic capability of ultrafiltrated fresh frozen plasma compared to cryoprecipitate

This in vitro study evaluated the potential hemostatic effect of fresh frozen plasma (FFP) ultrafiltration on clotting factors, coagulation parameters, and plasma properties. ABO-specific units of FFP (n = 40) were prepared for the concentrated FFP and cryoprecipitate. Plasma water was removed from FFP by ultrafiltration using a dialyzer with a pump running at a 300 mL/min. The aliquot of each concentrated FFP after 50, 100, 200, and 250 mL of fluid removal were measured the standard coagulation assay, clotting activity, and plasma properties to compare those parameters of cryoprecipitate. Concentrated FFP contained 36.5% of fibrinogen in FFP with a mean concentration of 7.2 g/L, lower than the cryoprecipitate level. The levels of factor VIII (FVIII), von Willebrand factor (VWF):antigen (Ag), and VWF:ristocetin cofactor (RCo) were also lower in concentrated FFP, whereas the levels of factor V, factor IX, factor XIII, antithrombin and albumin was higher in concentrated FFP. Maximum clot firmness (MCF) in thromboelastometry was approximately one-half of that in cryoprecipitate. Although the levels of VWF:Ag, VWF:RCo, and FVIII differed depending on the ABO blood types, fibrinogen levels, and MCF were not significantly different among the ABO blood groups in FFP and concentrated FFP.

Kif21a deficiency leads to impaired glomerular filtration barrier function

The renal glomerulus represents the major filtration body of the vertebrate nephron and is responsible for urine production and a number of other functions such as metabolic waste elimination and the regulation of water, electrolyte and acid–base balance. Podocytes are highly specialized epithelial cells that form a crucial part of the glomerular filtration barrier (GFB) by establishing a slit diaphragm for semipermeable plasma ultrafiltration. Defects of the GFB lead to proteinuria and impaired kidney function often resulting in end-stage renal failure. Although significant knowledge has been acquired in recent years, many aspects in podocyte biology are still incompletely understood. By using zebrafish as a vertebrate in vivo model, we report a novel role of the Kinesin-like motor protein Kif21a in glomerular filtration. Our studies demonstrate specific Kif21a localization to the podocytes. Its deficiency resulted in altered podocyte morphology leading to podocyte foot process effacement and altered slit diaphragm formation. Finally, we proved considerable functional consequences of Kif21a deficiency by demonstrating a leaky GFB resulting in severe proteinuria. Conclusively, our data identified a novel role of Kif21a for proper GFB function and adds another piece to the understanding of podocyte architecture and regulation.

Dynamics of non-Newtonian synovial fluid through permeable membrane with periodic filtration

This research measures the flow of synovial fluid through permeable membrane. It is assumed in this study that the ultrafiltration of blood plasma is a continuous function and repeatedly forms the action to keep synovial fluid normal in the joints. The novelty of this research is to analyze the rheology of synovial fluid under the periodic filtration rate within the membrane. To estimate the pressure and shear stress which are essential for the flow of synovial fluid between the synovial joints, mathematical modeling has been made for the synovial fluid flow through permeable membrane by the laws of mass and momentum and viscoelastic LPTT fluid model. The LPTT fluid has the viscoelastic effects in the presence of relaxation time, therefore for synovial fluid the present fluid model represents the best rheological properties. To find the analytical results for the rheology of the synovial fluid, a method proposed by Langlois is used. This research concludes that the pressure difference and transverse velocity are high when the periodic filtration is cosine type whereas the shear stress on the wall is high for sine type of filtration.

What's New in the Diagnosis of Periprosthetic Joint Infections: Focus on Synovial Fluid Biomarkers.

Periprosthetic joint infections are some of the leading causes of revision prosthetic surgery, accounting for 25% of failed total knee replacements and 15% of failed total hip replacements. The search for a biomarker that, together with clinical and radiological findings, could improve the management of such patients is currently a significant challenge for orthopaedic surgeons. Synovial fluid is a viscous and mucinous substance produced by the synovium, a specialized connective tissue that lines diarthrodial joints. Synovial fluid is an ultrafiltrate of plasma but also contains proteins secreted from the surrounding tissues, including the articular cartilage and synovium. Therefore, synovial fluid represents a source of disease-related proteins that could be used as potential biomarkers in several articular diseases. Based on these findings, the study of synovial fluid has been gaining increasing importance in recent years. This review aims to assess the accuracy and the limitations of the most promising synovial fluid biomarkers-i.e., Alpha-Defensin, Leukocyte Esterase, C-Reactive Protein, Interleukin-6, Calprotectin, Presepsin and Neopterin-in the diagnosis of PJI. Special attention will be given to emerging synovial biomarkers, which could soon be important in diagnosing PJIs.

Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice

Plasma ultrafiltration in the kidney occurs across glomerular capillaries, which are surrounded by epithelial cells called podocytes. Podocytes have a unique shape maintained by a complex cytoskeleton, which becomes disrupted in glomerular disease resulting in defective filtration and albuminuria. Lack of endogenous thymosin β4 (TB4), an actin sequestering peptide, exacerbates glomerular injury and disrupts the organisation of the podocyte actin cytoskeleton, however, the potential of exogenous TB4 therapy to improve podocyte injury is unknown. Here, we have used Adriamycin (ADR), a toxin which injures podocytes and damages the glomerular filtration barrier leading to albuminuria in mice. Through interrogating single-cell RNA-sequencing data of isolated glomeruli we demonstrate that ADR injury results in reduced levels of podocyte TB4. Administration of an adeno-associated viral vector encoding TB4 increased the circulating level of TB4 and prevented ADR-induced podocyte loss and albuminuria. ADR injury was associated with disorganisation of the podocyte actin cytoskeleton in vitro, which was ameliorated by treatment with exogenous TB4. Collectively, we propose that systemic gene therapy with TB4 prevents podocyte injury and maintains glomerular filtration via protection of the podocyte cytoskeleton thus presenting a novel treatment strategy for glomerular disease.

PROGNOSTIC ROLE OF THE BIOMARKER FOR SQUAMOUS CELL CARCINOMA ANTIGEN IN ORAL LICHEN PLANUS

Lichen planus refers to chronic dermatoses with manifestation in the oral mucosa. Its clinical manifestations are displayed as disruption of the immune system balance. A prolonged course of lichen planus causes deregulation of the cell growth gene, dysplasia of the epithelium of the oral mucosa and the development of squamous cell carcinoma. Identification of circulating biological markers in blood and saliva enables to detect stable and reliable predictors of clinical significance in the diagnosis and the prognosis of diseases of the oral mucosa, including the onset of tumor transformation. Squamous cell carcinoma (SCC) antigen is one of these cancer markers. Saliva is an "ultrafiltrate of blood plasma", which makes it possible to evaluate biological markers by a safe non-invasive method. The aim of this study is to assess the concentration of squamous cell carcinoma antigen in mixed saliva samples of patients with various forms of lichen planus at the stages of diagnosis and treatment. Materials and methods. 47 women with a clinical diagnosis of "oral lichen planus" were examined and randomized in groups. They described the dental status, identified the causes of chronic injury, and made a comprehensive treatment plan. Monitoring was carried out at the diagnostic stage, after 14 and 90 days. During the first visit and after treatment, unstimulated mixed saliva was collected on an empty stomach. Results. During the diagnosis, the content of SC in the oral fluid of patients with lichen planus was <500 mcg/ml (489 mcg/ml) and a decrease in its concentration after treatment is characteristic of a benign course and susceptibility to therapy. The concentration of the marker >500 mcg/ml (527 mcg/ml) and an increase in the value after the treatment course indicates a severe recurrent nature of the disease and low efficacy of prescribed medications. Conclusion. The study of squamous cell carcinoma (SCC) antigen in oral fluid expands the applications of the biomarker in determining the prognosis of the course and effectiveness of therapy for oral lichen planus.

CT-Guided Pericardial Drainage: A Safe and Viable Alternative to Ultrasound-Guided Drainage.

Pericardial effusions result from a wide range of pathology, with presentations ranging from an incidental finding to a life-threatening emergency. Common causes of pericardial effusions include infection, inflammatory conditions, neoplasm, trauma, and iatrogenic.[1] The pericardium, which is a fibroelastic sac containing the heart and the proximal great vessels, normally contains 10 to 50 mL of a serous ultrafiltrate of plasma produced by the visceral pericardium.[2] The pericardium and the pericardial fluid together serve to prevent sudden dilatation of the heart and significant movement of the great vessels, minimize friction between the heart and the surrounding structures, and help prevent the spread of disease from the pleura or the lungs.

Metabolomics of Cerebrospinal Fluid in Multiple Sclerosis Compared With Healthy Controls: A Pilot Study.

BackgroundMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading to the loss of myelin and axons. Diagnosis is based on clinical findings, MRI, and analysis of cerebrospinal fluid (CSF). CSF is an ultrafiltrate of plasma and reflects inflammatory processes in the CNS. The aim of this study was to perform metabolomics analysis of CSF in patients after the first attack of MS and healthy controls and try to find new specific analytes for MS including those potentially predicting disease activities at the onset.MethodsWe collected CSF from 19 patients (16 females, aged 19–55 years) after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS and CSF of 19 controls (16 females, aged 19–50 years). Analyses of CSF samples were provided using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector (TripleTOF 5600, AB Sciex, Canada).ResultsApproximately 130 selected analytes were identified, and 30 of them were verified. During the targeted analysis, a significant decrease in arginine and histidine and a less significant decrease in the levels of asparagine, leucine/isoleucine, and tryptophan, together with a significant increase of palmitic acid in the patient group, were found.ConclusionWe observed significant differences in amino and fatty acids in the CSF of newly diagnosed patients with MS in comparison with controls. The most significant changes were observed in levels of arginine, histidine, and palmitic acid that may predict inflammatory disease activity. Further studies are necessary to support these findings as potential biomarkers of MS.

Glomerular hyperfiltration.

Circulating blood is filtered across the glomerular barrier to form an ultrafiltrate of plasma in the Bowman's space. The volume of glomerular filtration adjusted by time is defined as the glomerular filtration rate (GFR), and the total GFR is the sum of all single-nephron GFRs. Thus, when the single-nephron GFR is increased in the context of a normal number of functioning nephrons, single glomerular hyperfiltration results in 'absolute' hyperfiltration in the kidney. 'Absolute' hyperfiltration can occur in healthy people after high protein intake, during pregnancy and in patients with diabetes, obesity or autosomal-dominant polycystic kidney disease. When the number of functioning nephrons is reduced, single-nephron glomerular hyperfiltration can result in a GFR that is within or below the normal range. This 'relative' hyperfiltration can occur in patients with a congenitally reduced nephron number or with an acquired reduction in nephron mass consequent to surgery or kidney disease. Improved understanding of the mechanisms that underlie 'absolute' and 'relative' glomerular hyperfiltration in different clinical settings, and of whether and how the single-nephron haemodynamic and related biomechanical forces that underlie glomerular hyperfiltration promote glomerular injury, will pave the way toward the development of novel therapeutic interventions that attenuate glomerular hyperfiltration and potentially prevent or limit consequent progressive kidney injury and loss of function.

Myocardial Edema Provides a Link Between Pulmonary Arterial Hypertension and Pericardial Effusion.

Myocardial Edema Provides a Link Between Pulmonary Arterial Hypertension and Pericardial Effusion.

Генезис структурно-функціональних порушень та гідростатична модель кісти Бейкера

Вступ. Колінний суглоб оточують різноманітні кістоподібні утворення (КПУ) — бурси, які у нормі клінічно не проявляються. Усі синовіальні порожнини, до яких, зокрема, належать колінний суглоб та бурси, які оточують колінний суглоб, містять синовіальну рідину. Синовіальна рідина є ультрафільтратом плазми крові і складається із білків та інтерстиціальної рідини. У літературі описані бурси, що оточують колінний суглоб, висвітлена ультразвукова класифікація кіст Бейкера залежно від стадії перебігу, яка запропонована І.М. Даниловою [10], та класифікація кістозного переродження меніска, але відсутня інформація щодо патофізіологічних та гістохімічних змін, які відбуваються у КПУ ділянки колінного суглоба, а також відсутня патофізіологічна модель КПУ ділянки колінного суглоба, яка б відображала природу даного захворювання з точки зору фізико-біохімічних процесів. Матеріали та методи. У травматологічному відділенні клініки ­ушкоджень Військово-медичного клінічного центру Північного регіону з початку 2016 року під спостереженням знаходилось 15 пацієнтів із клінічної картиною кістоподібного утворення ділянки колінного суглоба, що підтверджено інструментальними методами обстеженнями: ультразвуковим дослідженням (УЗД), магнітно-резонансною томографією (МРТ) та спіральною комп’ютерною артрографією (СКТА) колінного суглоба. Із них литково-напівперетинчастий бурсит спостерігався у 9 пацієнтів, кісти менісків — у 5 пацієнтів, бурсит переднього відділу колінного суглоба — в 1 пацієнта. Серед пацієнтів 11 чоловіків та 4 жінки. Середній вік пацієнтів становив 43,5 року. Об’єктом дослідження були кістоподібні утворення ділянки колінного суглоба. Усім хворим із КПУ проводили комплексне інструментальне обстеження, яке включало УЗД, СКТА, МРТ, вимірювання внутрішньосуглобового та внутрішньокістозного тисків за допомогою контактного манометра фірми Stryker та надалі — діагностично-лікувальної артроскопії. На основі отриманих даних УЗД проводився розподіл хворих на 4 групи, що базується на процентному відношенню внутрішньопросвітних нашарувань (включень) до загального просвіту КПУ, що дало можливість сформувати нову класифікацію КПУ ділянки колінного суглоба для вибору того чи іншого методу лікування. Результати та обговорення. Для формування та прогресування КПУ має значення підвищений тиск, який становить у середньому 29 мм рт.ст. у положенні згинання та до 58,4 мм рт.ст. у положенні розгинання. Виходячи із попередніх даних, на нашу думку, критичним показником тиску, при якому може настати розрив кісти Бейкера, є тиск більше 60 мм рт.ст. Зазвичай таке ускладнення виникає при тривалому існуванні кісти, коли тривала адсорбція білкових молекул на стінці кісти призводить до адсорбційного зниження міцності та зниження поверхневого натягу — ефект Ребіндера. Висновки. Враховуючи дані біохімічних процесів, УЗД та ендоскопії кіст Бейкера на різних стадіях, ми дослідили, що сама стінка кісти не потовщується, а відбувається пристінкове нашарування білкових молекул із формуванням глобул, які і формують так звану псевдостінку. У подальшому ці нашарування починають формувати перетинки між протилежними стінки, ущільнюватись, що призводить до камерності КПУ. На пізніх стадіях дані нашарування переважають над просвітом КПУ. Запропонована нами класифікація заснована на визначенні процентного відношення внутрішньопросвітних нашарувань до загального просвіту КПУ у двох зрізах та відображає основні морфологічні зміни, що дає можливість визначити оптимальний метод лікування даного кістоподібного утворення та широкого практичного використання у травматології та ортопедії.

The glymphatic system

All biological processes including movement, digestion, and thought require energy, and the metabolic activity necessary to generate that energy also generates waste. Metabolic by-products, including a variety of proteins, accumulate in the tissue and can be harmful if not removed. Throughout the body, the lymphatic system is responsible for clearing metabolic waste from the tissue (Figure 1). An ultrafiltrate of blood plasma constantly enters the tissue from the microvasculature and percolates through the tissue before uptake by lymphatic capillaries. Once in these capillaries, a series of lymphatic vessels, pumps, and valves ensures directional fluid movement, ultimately draining the lymph containing waste products back into the venous circulatory system. The liver can be regarded as the ultimate recycling station in the body, where these waste products are either degraded or reused.

MO730THORACIC BIOIMPEDANCE AS AN INNOVATIVE TOOL TO DETECT CHANGES IN BLOOD PRESSURE DURING HEMODIALYSIS

Abstract Background and Aims Blood pressure (BP) variability is an important cardiovascular risk factor that contributes to the high burden of cardiovascular mortality in hemodialysis (HD) patients. Ultrafiltration rate (UFR) and plasma refill rate modify the extracellular volume (ECV), which is a major determinant of the systolic BP. Segmental bioimpedance of the thoracic region addresses the central volume compartment of the body. We hypothesize that changes in bioimpedance reflect changes in BP and that thoracic measurements are more accurately in detecting intradialytic BP changes compared to whole body bioimpedance. Method During two consecutive short-term interval HD sessions, thoracic bioimpedance signal was registered continuously from predialysis until the end of the session. Corresponding BP, whole body bioimpedance and ultrafiltration volume (UFV) after the start and at the end of dialysis was registered. After outlier detection, valid raw bioimpedance data [Ohm] at 8 and 160 kHz for thoracic measurements, and 5 and 200 kHz for whole body measurements, were taken into further analysis. Dialysis sessions were divided into 3 groups according to the development of the systolic BP: a drop ≥ than 20 mmHg was defined as a hypotensive session, an increase ≥ 10 mmHg was considered as a hypertensive session. Pearson correlation analysis was applied (r, p-value) to the relative data, calculated as a percentage from the start value. Results From 2 dialysis centres, a total of 46 HD patients were enrolled in the study (65.2% male, mean age 71 ± 12.6 years, mean dialysis vintage 4 ± 3.9 years), which resulted in 89 dialysis sessions to analyse. Mean systolic BP after start of dialysis was 133.2 ± 20.7 mmHg and mean UF volume was 1817.5 ± 801.5 mL. 23 sessions showed a hypotensive gradient from the start till the end of dialysis, and 13 sessions progressed with an increase of more than 10 mmHg. When the 8 kHz curve was plotted according to the 3 BP groups, a more plane increase in thoracic bioimpedance signal was observed in the group with a normal tension course (Figure 1). There was a significant relationship between UFR and changes in relative bioimpedance data, as well as thoracic (r = .49 at 8 kHz, r = .46 at 160 kHz, all ps < .001), as whole body bioimpedance (r = .58 at 5 kHz, r = .52 at 200 kHz, all ps < .001). UFV correlated with changes in systolic BP (r = -.31, p < .01). Both bioimpedance techniques correlated with each other (r = .38, p = .001 for low frequencies; r = .29, p < .01 for high frequencies). Where the relative thoracic bioimpedance signal correlated with changes in systolic BP (r = -.35 at 8kHz, -.32 at 160 kHz, all ps < .01) (Figure 2), whole body did not. Conclusion Thoracic bioimpedance is associated with intradialytic BP changes, whereas whole body bioimpedance is not. Thoracic bioimpedance has the potential to function as an important diagnostic and predictive tool in BP variability during HD.

Diagnostic significance of serum and salivary lipid levels in oral precancer and oral cancer.

Introduction:Lipids are one of the major constituents of the cell. Variations in the serum lipids have been considered a cofactor of carcinogenesis, as lipids play a crucial role in cell integrity. Saliva is an ultrafiltrate of plasma and correlates with the serum, which may be used as an alternate method of serum lipid level estimation. The study was conducted to find any correlation between serum and salivary lipid levels and to evaluate the changes in serum and salivary lipid levels in oral precancer and cancer patients.Aims and Objectives:This study aimed to evaluate the changes in serum and salivary lipid levels in oral precancer and cancer patients and to correlate salivary lipid levels with serum lipid levels.Materials and Methods:The study was an in vivo study conducted on randomly selected 129 patients with oral cancer and oral precancer. The selected subjects were divided into four groups as Group 1 – healthy control, Group 2 – oral submucous fibrosis, Group 3 – leukoplakia, and Group 4 – oral cancer. Serum and salivary lipid levels were estimated biochemically and statistically analyzed for any correlation with oral precancer and cancer.Results:Lipid level estimation showed no statistically significant difference on comparison of intergroup serum and saliva total cholesterol level and high-density lipoproteins among all four groups, whereas intergroup comparison of serum and saliva triglycerides (TG) levels among the four groups showed a statistically significant difference in saliva TG level. The correlation of serum and salivary lipid levels showed a significant positive correlation.Conclusion:In the present study association between serum/salivary lipid levels and oral precancer and oral cancer could not be established. A positive association was there in serum and salivary lipids hence salivary lipid levels may be used as a noninvasive technique for serum lipid level estimation.

Electromembrane extraction as a new approach for determination of free concentration of phenytoin in plasma using capillary electrophoresis

Electromembrane extraction is a new membrane-based extraction method in which charged compounds are extracted by an electric field. So far, this method has been used to extract and isolate a variety of acidic and basic drugs from various samples, including blood and plasma. However, in this procedure, it is not yet clear whether only unbound fraction of a drug is extracted or the total drug. The aim of this study is to reveal the nature of drug extraction in the presence of plasma proteins. To determine the nature of the extraction, the electromembrane extraction was performed from plasma solutions of phenytoin with concentrations 0.03 and 1.0μg/mL, then the result was compared with the values obtained from the electromembrane extraction of ultrafiltrate of the same solutions (free concentration) and protein-free ultrafiltrate of plasma with final concentration of 0.03 and 1.0μg/mL (total concentration). For this purpose, EME followed by capillary electrophoresis coupled with diode array detection was optimized and validated. The results showed that the electromembrane extraction method was only able to extract the unbound fraction of phenytoin from plasma samples. The method was validated over a concentration range of 0.03-4μg/mL. The inter and intra-assay precisions were less than 6.7%. The phenytoin protein binding was also determined to be in agreement with the literature data and confirms the validity of this method. This sensitive and quick EME approach for determining the free concentration of a phenytoin, can be a good alternative to classic methods for therapeutic drug monitoring and pharmacokinetic studies.

The epicardium as a biological filter of the heart

In the epicardium of many mammals, animals, including humans, were found to have typical arteriovenular anastomoses. However, they do not correspond to the description of those direct anastomoses between arteries and veins located under the epicardium, which were previously identified. The authors who described them, using injection methods, showed the passage of carcass suspension from sub-epicardial arteries to sub-epicardial veins. But they could not accurately identify the type of vessels carrying out these connections. It is possible that these are arteriovenular anastomoses, since their diameter not exceeds the diameter of the blood capillaries. At the same time, it was shown that the vascular structures of the epicardium carry out the separation of the blood in the coronary artery system. As a result, blood with high hematocrit and freed from most various analytes and neutrophilic granulocytes enters the microvascular bed of the myocardium. The ultrafiltrate of the blood plasma in the sub-epicardial loose connective tissue undergoes biodegradation and is utilized in the lymphatic micro vessels. The aim of the work is the morphological and functional substantiation of the concept about of the epicardium as a biological filter of the heart. The vascular bed of the epicardium of hearts of mature dogs was studied (n=5), revealed by various routine histological and original intra- and extravascular methods. It is proved that the microvascular bloodstream of the sub-epicardial connective tissue has pronounced organ specificity. It is determined by the presence of arteriovenular anastomoses and permanent plasma capillaries, as well as the high permeability of all vascular components. The microvascular bed of the epicardium causes an ascending dilatation of the coronary arteries and contributes to ultrafiltration of a significant amount of blood plasma into the sub-epicardial interstitial space. Thus, the process of the separation of the blood is carried out, as a result of which blood with high hematocrit and free of neutrophilic granulocytes enters the myocardium. In the epicardial connective tissue, analytes accumulate that cannot be resorbed by venous micro vessels. This «biological debris» undergoes destruction in the sub-epicardial connective tissue, which proves the role of the epicardium as a biological filter of the heart.

Decoding the differentiation of mesenchymal stem cells into mesangial cells at the transcriptomic level

BackgroundMesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells, to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells.ResultsSeveral ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.ConclusionsA systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.

The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-induced Hypertension.

Purinergic receptors play a central role in the renal pathophysiology of angiotensin II-induced hypertension, since elevated ATP chronically activates P2X7 receptors in this model. The changes induced by the P2X antagonist Brilliant blue G (BBG) in glomerular hemodynamics and in tubulointerstitial inflammation resulting from angiotensin II infusion were studied. Rats received angiotensin II (435 ng kg−1 min−1, 2 weeks) alone or in combination with BBG (50 mg/kg/day intraperitoneally). BBG did not modify hypertension (214.5 ± 1.4 vs. 212.7 ± 0.5 mmHg), but restored to near normal values afferent (7.03 ± 1.00 to 2.97 ± 0.27 dyn.s.cm−5) and efferent (2.62 ± 0.03 to 1.29 ± 0.09 dyn.s.cm−5) arteriolar resistances, glomerular plasma flow (79.23 ± 3.15 to 134.30 ± 1.11 nL/min), ultrafiltration coefficient (0.020 ± 0.002 to 0.036 ± 0.003 nL/min/mmHg) and single nephron glomerular filtration rate (22.28 ± 2.04 to 34.46 ± 1.54 nL/min). Angiotensin II induced overexpression of P2X7 receptors in renal tubular cells and in infiltrating T and B lymphocytes and macrophages. All inflammatory cells were increased by angiotensin II infusion and reduced by 20% to 50% (p < 0.05) by BBG administration. Increased IL-2, IL-6, TNFα, IL-1β, IL-18 and overexpression of NLRP3 inflammasome were induced by angiotensin II and suppressed by BBG. These studies suggest that P2X7 receptor-mediated renal vasoconstriction, tubulointerstitial inflammation and activation of NLRP3 inflammasome are associated with angiotensin II-induced hypertension.