Capillary Membrane Research Articles

NEGATIVE PRESSURE PULMONARY EDEMA AFTER GENERAL ANESTHESIA

Abstract Negative pressure pulmonary oedema is a type of non-cardiogenic pulmonary oedema caused by strong inspiratory effort to overcome obstruction in the upper airways. The main mechanisms responsible for the pathophysiology are the increase in pulmonary capillary hydrostatic pressure and the increase in capillary membrane permeability that develops after the negative intrathoracic pressure increases with inspiratory effort. Although all causes that may lead to upper airway obstruction may play a role in the etiology, the most common factor is laryngospasm that develops during awakening from anaesthesia. Young male smokers under general anaesthesia are more at risk. Onset may vary from a few minutes to several hours after extubation or relief of laryngospasm. It leads to an acute respiratory failure that is potentially life-threatening and usually requires follow-up and treatment in the intensive care unit. The first step in treatment is to relieve airway obstruction and provide oxygen support. Positive pressure ventilation and use of diuretics are beneficial and usually tend to improve within 24-48 hours. The mortality rate is reported to be around 5% in case analysis reports of recent years. Since it is observed more frequently in anaesthetised patients, early diagnosis and treatment in the postoperative period is important. The aim of this review is to present a current perspective on negative pressure pulmonary oedema in the light of the literature.

Enhancing the energy efficiency of land vehicles air conditioning units through a new evaporative membrane cooler

Led by the growing need for energy efficiency in the air conditioning systems on land vehicles, this paper proposes an original approach that integrates evaporative cooling technologies into the existing systems. In detail, the new evaporative membrane system adds to the traditional one an auxiliary kit composed of a water reserve, a circulation pump, a heat exchanger, and an innovative capillary crossflow membrane cooler. The evaporation process is used to both pre-cool the air flow to the condenser, thus lowering the refrigerant condensation temperature, and also to supply refreshed water for pre-chilling the renewal air. The proposed architecture is particularly feasible for vehicular applications where a water reservoir already exists or where it is possible to install and maintain one. The designed membrane cooler grants high mass transfer efficiency, compactness (membrane surface-to-volume ratio around 1000 m2/m3) and manages high air flow rates while minimizing pressure loss. It is composed by organized layers of polypropylene capillaries where water flows, and plastic spacers for the airflow.First, the vapor and heat transfer mechanisms involved are investigated and the cooler’s mathematical model is described. Numerical results show that a wet-bulb effectiveness exceeding 0.85 can be reached.Subsequently, an assessment of energy performance indicators for a motorhome application is conducted within the MATLAB© Simulink environment. This involves a comparative analysis between the proposed system and the conventional standalone one. The considered contactor has a total membrane area of 8.32 m2 and handles 1200 m3/h of air and 150 kg/h of water. Results indicate that the efficiency ratio and the energy savings of the two systems decrease as the external air humidity increases even though the average energy efficiency ratio of the new system remains significantly higher. Mechanical energy savings are very interesting and decrease as the external air humidity increases: they are about 36–38 % within the humidity range [40–50 %], 26–30 % within the range [50–60 %], and 17–21 % within the range [60–70 %]. The corresponding water consumptions are between 2 kg/h and 6.5 kg/h, and they increase as air humidity decreases.Due to its simple architecture and high performance, this system is very promising in applications for motorhome, city buses, trains, and trucks.

Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2

BackgroundPost COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients’ reported symptomatology is still unclear.MethodsConsecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function.ResultsWe evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102–123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap.ConclusionsIn patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Features of the course of acute cerebral stroke in patients with type 2 diabetes

Acute stroke is a major public health problem in both developing and developed countries and has detrimental effects on the individual, family, and societal levels. Ischemic stroke is a disease with significant prevalence, high disability, high mortality, and high recurrence rate. Diabetes mellitus is one of the most serious and most common chronic diseases today, causing life-threatening complications that lead to disability. Among these complications, one of the most common is acute stroke. People with diabetes are at a 1.5–2 times higher risk of acute ischemic stroke compared to people without this disease. Hyperglycemia doubles the risk of recurrent stroke and increases the risk of death or disability after ischemic stroke. There are several possible mechanisms by which diabetes leads to acute stroke, including cardiac embolism (atrial fibrillation), endothelial dysfunction, increased arterial stiffness at an early age, systemic inflammation and thickening of the capillary basement membrane. Controlling glucose levels through lifestyle changes or medications and modifying other associated risk factors (such as hypertension and dyslipidemia) are critical steps to the effective stroke prevention.

Histology of fetal lungs at different gestational age

The lecture is devoted to the morphological characteristics of the maturation of lung tissue structures in the fetal period. Fetal histology of the lungs presents the intrauterine development of lung tissue in four successive stages: pseudoglandular, canalicular, saccular and alveolar, each has specific morphological criteria. The following morphological features are predetermined: the development of alveolar epithelium, the ratio of mesenchyme towards the area in alveolar spaces, the degree of proliferation and location of vessels of the microcirculatory bed towards prealveolar partitions. During the fetal period the alveolar columnar epithelium is flattened and differentiates into alveolocytes type I and II, the area of the mesenchyme gradually decreases and by the birth of a full-term newborn kid it is present mainly in the thickness between the alveolar septa, microcirculation vessels, initially laying deep in the thickness of the mesenchymal tissue, gradually proliferate, approach the pre-alveolar epithelium, channeling it with the formation of alveolar capillary membranes. Air exchange in the lung tissue is mainly provided with two factors: the presence of second-order alveolocytes capable of producing surfactant, and a sufficient formation of alveoli as well. This work summarizes the basics of fetal lung histology with the demonstration of histological preparations of the lungs at different stages of intrauterine development.

Electrifying Ba0.5Sr0.5Co0.8Fe0.2O3−δ for focalized heating in oxygen transport membranes

Industry decarbonization requires the development of highly efficient and flexible technologies relying on renewable energy resources, especially biomass and solar/wind electricity. In the case of pure oxygen production, oxygen transport membranes (OTMs) appear as an alternative technology for the cryogenic distillation of air, the industrially-established process of producing oxygen. Moreover, OTMs could provide oxygen from different sources (air, water, CO2, etc.), and they are more flexible in adapting to current processes, producing oxygen at 700–1000 °C. Furthermore, OTMs can be integrated into catalytic membrane reactors, providing new pathways for different processes. The first part of this study was focused on electrification on a traditional OTM material (Ba0.5Sr0.5Co0.8Fe0.2O3−δ), imposing different electric currents/voltages along a capillary membrane. Thanks to the emerging Joule effect, the membrane-surface temperature and the associated O2 permeation flux could be adjusted. Here, the OTM is electrically and locally heated and reaches 900 °C on the surface, whereas the surrounding of the membrane was maintained at 650 °C. The O2 permeation flux reached for the electrified membranes was ∼3.7 NmL min−1 cm−2, corresponding to the flux obtained with an OTM non-electrified at 900 °C. The influence of depositing a porous Ce0.8Tb0.2O2−δ catalytic/protective layer on the outer membrane surface revealed that lower surface temperatures (830 °C) were detected at the same imposed electric power. Finally, the electrification concept was demonstrated in a catalytic membrane reactor (CMR) where the oxidative dehydrogenation of ethane (ODHE) was carried out. ODHE reaction is very sensitive to temperature, and here, we demonstrate an improvement of the ethylene yield by reaching moderate temperatures in the reaction chamber while the O2 injection into the reaction can be easily fine-tuned.

Vasoprotective Effect of Sulodexide in Diabetic Retinopathy

Diabetes is a group of metabolic diseases, considered a lifestyle disease. Diabetic retinopathy is the leading cause of blindness in working-age adults worldwide. Pathogenetically, due to the changed anionic charge, collagen gradually replaces glycosaminoglycans (GAG) in the basement membrane of retinal capillaries, affecting vascular permeability. Clinically, these changes cause leakage from the retinal capillaries, which leads to the development of microaneurysms and, consequently, the formation of hard effusions (HE). Sulodexide is a glycosaminoglycan containing 80% of small molecular weight, fast moving heparin fraction (FMH) and 20% of dermatan sulfate. An important target of sulodexide's action are vascular endothelial cells, and its protective effect is partially related to the preservation and reconstruction of the glycocalyx structure on the surface of the endothelial layer cells. Additionally, sulodexide has been documented to strengthen the glycocalyx of retinal arterioles in people with diabetes. These findings suggest that sulodexide holds promise as a potential therapeutic agent for the treatment of diabetic retinopathy.

Nursing Care Process for patients with Pneumonia and Arterial Hypertension in the Emergency Department of a hospital in Lima

The present study work was applied to a patient with a medical diagnosis: pneumonia and arterial hypertension in the emergency service. The objective of the present work was to apply the nursing care process to an older adult with Pneumonia. The assessment was carried out with the guide based on the 11 functional patterns of Marjori Gordon. After identifying the problems, 11 nursing diagnoses are enunciated taking into account the NANDA taxonomy and the following diagnoses are prioritized: Impairment of gas exchange related to changes in the capillary alveolus membrane evidenced by O2 Sat: 91% Abnormal arterial blood gas (PO2: 63 mmHg) abnormal respiratory pattern, respiratory rate 26 per minute, ineffective cleaning of the airways related to changes in the capillary alveolus membrane evidenced by altered respiratory pattern, altered respiratory rate and abnormal respiratory sounds, and CP Hypertension. Subsequently, planning is carried out using the NOC and NIC taxonomy, the interventions and planned activities are executed. The results obtained gave a score of +1, +2 and +2. It is concluded that the nursing care process is the application of care in a systematic and orderly manner, helping to provide quality care and humanism.

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as “long COVID”. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues. In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.Graphical

Pathogenesis of ARIA

AbstractBackgroundAD is characterised pathologically by the deposition of amyloid‐beta peptides in the extracellular spaces of the brain as plaques and cerebral amyloid angiopathy (CAA). Observations on human post‐mortem brains and experimental studies in mice demonstrate that amyloid‐beta is deposited in the basement membranes of capillaries and basement membranes of arterial smooth muscle cells, within the Intramural Periarterial Drainage (IPAD) pathways.MethodPathological studies performed on human post‐mortem brains from the first ELAN trial demonstrated that after active immunization against amyloid‐beta, despite the disappearance of plaques, CAA worsened and both Abeta 40 as well as Abeta42 were present in the vascular wall. This suggests that Abeta42 solubilised from plaques has become entrapped in the IPAD pathways.ResultExperimental immunization in rodents against a cerebral protein demonstrate that within 24h, immune complexes are formed in the basement membranes of capillaries, impairing IPAD. By 7 days after immunization, inflammatory cuffs of perivascular cells are present, but, in a normal adult mouse, IPAD is restored.ConclusionThis suggests that clearance of fluid and solutes can be restored even in the context of immune cell recruitment if the vascular wall is healthy.

Multilamellated Basement Membranes in the Capillary Network of Alveolar Capillary Dysplasia

A minimal diffusion barrier is key to the pulmonary gas exchange. In alveolar capillary dysplasia (ACD), a rare genetically driven disease of early infancy, this crucial fibrovascular interface is compromised while the underlying pathophysiology is insufficiently understood. Recent in-depth analyses of vascular alterations in adult lung disease encouraged to extend these studies to ACD and compare the changes of the microvasculature.Lung tissue samples of children with ACD (n=12), adults with non-specific interstitial pneumonia (n=12), and controls (n=20) were studied using single gene sequencing, immunostaining, exome sequencing, and broad transcriptome profiling in addition to analysis of the vasculature by transmission electron microscopy. In ACD, pulmonary capillary basement membranes were hypertrophied, thickened, and multilamellated. Transcriptome profiling revealed increased CDH5, COL4A1, COL15A1, PTK2B, and FN1 and decreased VIT expression, confirmed by immunohistochemistry. In contrast, NSIP samples showed a regular basement membrane architecture with preserved VIT expression but also increased COL15A1+ vessels.This study provides insight into the ultrastructure and pathophysiology of ACD. The lack of normally developed lung capillaries seems to cause a replacement by COL15A1+ vessels, a mechanism recently described in interstitial lung disease. The VIT loss and FN1 overexpression might contribute to the unique appearance of basement membranes in ACD. Future studies are needed to explore the therapeutic potential of downregulating the expression of FN1 and balancing of VIT deficiency.

Application of polypropylene microfiltration membranes for separation of wastewater from car wash

In the final stage of washing the car is waxed and rinsed with demineralized water, however, at an initial stage reusing treated effluents as process water is possible. In the current work, the application of microfiltration (MF) polypropylene (PP) membranes for treatment of carwash wastewater was investigated. To compare the transport properties, more hydrophobic PTFE capillary membranes were also used. The examined process is restricted by the fouling phenomenon, which has been thoroughly studied by filtering both the synthetic and real wastewaters. The use of different types of foaming agents and hydrowaxes, allowed to found that the membranes fouling was caused not only by the impurities removed from the car, but also by the mixtures of commercial washing agents. As a result, the permeate flux was quickly reduced, to a level of 100–200 LHM for PP membrane and to 50–150 LHM for PTFE membrane (TMP = 0.05 MPa). Regardless of the degree of feed contamination, the clean permeate with turbidity of 0.2–0.8 NTU was obtained. In the case PTFE membrane, the permeate turbidity was at a level of 2–3 NTU. The tested wastewaters (5–100 NTU) contained the particles with the size in the range of 0.1–400 μm. The removal of larger particles by prefiltration was found to increase the membranes fouling. It has been noted that rinsing the modules with water was not effective. Nevertheless, the membranes were cleaned using alkaline solutions (pH = 11.5–12.0) used at the car wash station to remove insects and to wash the wheel. This procedure was less effective for PTFE membranes, which experienced significantly greater irreversible fouling. It has been shown that the PP membranes used, in addition to removing turbidity, ensured the retention of Escherichia coli in almost 100%.

SAT159 A Unique Case Of IGF-2 Induced Hypoglycemia As First Manifestation Of Hepatocellular Carcinoma

Abstract Disclosure: I. Ali: None. M. Alnaher: None. A. Arida: None. Introduction: Hypoglycemia is one of the manifestations of non-islet cell tumor-induced hypoglycemia (NICTH). In hepatocellular carcinoma (HCC), it has been reported in 4-27% of patients, and it is associated with poor prognosis. Case: Patient is a 70-years-old Female with past medical history of prediabetes and untreated Hepatitis C infection who presented with sever weakness and was found to have blood glucose of 37. She was started on Dextrose 10% with improvement of her symptoms. During hospital course she had recurrent episodes of symptomatic hypoglycemia. Patient denied any family history of diabetes with no access to diabetes medication. Blood work showed elevated AST, ALT with low albumin, low prealbumin and AM cortisol 13, Sulfonylureas screen is Negative. Result of 72 hours hypoglycemia protocol while blood glucose level was 48 mg/dl as follow: Proinsulin, Intact 1.6 mmol/L (Ref: less than 8.0), insulin like growth factor -1 (IGF-1): 10 ng/ml (26-226), IGF-2: 69 ng/ml (180-580) so IGF-2/IGF-1 ratio of 6.9Insulin: 0.2 uIU/ml (1.9-23), C-Peptide 0.1 ng/ml (0.5-3.3) and Beta hydroxybutyrate: 0.1 mmol/L. CT abdomen: 7.0 x 7.2 x 10.5 cm right hepatic lobe mass with extension to right portal vein that is most consistent with hepatocellular carcinoma with background liver cirrhosis with portal hypertension without ascites. Right hepatic artery tumor biopsy showed moderately differentiated HCC. Patient was started on steroid therapy then octreotide. Multidisciplinary meeting discussed in details treatment options and prognosis including treatment of her cancer with surgery vs chemoradiation therapy, but patient and her family opted for DNR/DNI, and patient passed away during that admission. Discussion: Even though HCC-related hypoglycemia is a known phenomenon, knowledge about prevention and treatment is lacking. The suggested mechanism of hypoglycemia in NICTH include increased consumption of glucose by tumor in malnourished patients with low glycogen deposits and defective gluconeogenesis or may be caused by IGF-2 overproduction that crosses capillary membranes and stimulates insulin receptor. Hypoglycemia work up reveals low levels of insulin, pro-insulin, C-peptide, and β-hydroxybutyrate. Levels of GH and IGF-1 will also be low due to the suppressive effect of IGF-2. Total IGF-2 may be elevated or normal but the ratio of IGF-2/IGF-1 is usually elevated 3:1. Management of an IGF-2 producing tumor with surgical resection, radiation, and/or chemotherapy can potentially resolve hypoglycemia. Medical therapy with glucocorticoids has been utilized by promoting hepatic gluconeogenesis and lipolysis and reducing peripheral glucose uptake. Glucocorticoids also help to decrease the levels of IGF-2 either by decreased tumor production or increased clearance. Case reports have documented the use of glucagon, growth hormone, and octreotide, however, effects are limited. Presentation: Saturday, June 17, 2023

Exposure to Fumes of a Vegetable Margarine for Frying: Respiratory Effects in an Experimental Model.

Deep frying is one of the strongest emission sources into indoor air. A vegetable margarine has recently been used in commercial kitchens. This study investigated the respiratory effects of exposure to its fumes in an experimental model. A setup with glass chambers was constructed. A chamber housed a fryer. The fumes were transported to the other chamber where 24 Wistar albino rats were placed in four randomized groups: acute, subacute, chronic, and control for the exposure durations. PM10 concentration in the exposure chamber was monitored to ensure occupational levels were obtained. Sacrification was performed 24 h after exposure. Lung, trachea, and nasal concha specimens were evaluated by two blinded histologists under a light microscope with hematoxylin-eosin. Mild mononuclear cell infiltration, alveolar capillary membrane thickening, alveolar edema, and diffuse alveolar damage, along with diffuse hemorrhage, edema, and vascular congestion in the interstitium were observed in the acute and subacute groups, and were overexpressed in the chronic group, whereas normal lung histology was observed in the control group. The results indicate that exposure to fumes of vegetable margarine for frying in commercial kitchens may cause pulmonary inflammation that becomes severe as the duration of the exposure increases.

Intensive Management of A 21-Year-Old Male Patient with Acute Respiratory Failure Due to Near Drowning: A Case Report

Background: The mechanism of near drowning involves decreased lung compliance and aspiration of water into the lungs, which damages surfactants and disrupts alveolar capillary membranes. This leads to the development of alveolar oedema, and ventilation-perfusion mismatch, which causes hypoxemia leading to acute respiratory distress syndrome (ARDS) and cause other organ dysfunction and death.
 Case presentation: The patient was found drowned by his friends while on vacation and swimming in the river. Initial physical examination in the ED obtained a Glasglow coma scale (GCS) score of 14/15 (E3-V5-M6), blood pressure 124/70 mmHg, and pulse 124 beats/min. The patient breathed spontaneously 25 breaths/min with oxygen saturation (SpO2) of 90% on room air. The patient was initially managed with oxygenation using a non-rebreathing mask (NRM semi-fowler positioning and peripheral access. Chest X-ray and other radiologic examinations, including a brain CT scan, were performed before the patient was immediately transferred to the ICU, and there was no evidence of other trauma. During the 9 days of intensive management in the ICU, there was a good improvement from GCS 14 to 15.
 Conclusion: Intensive management of a 21-year-old male patient with acute respiratory failure due to near drowning.

Computational pulmonary edema: A microvascular model of alveolar capillary and interstitial flow.

We present a microvascular model of fluid transport in the alveolar septa related to pulmonary edema. It consists of a two-dimensional capillary sheet coursing by several alveoli. The alveolar epithelial membrane runs parallel to the capillary endothelial membrane with an interstitial layer in between, making one long septal tract. A coupled system of equations uses lubrication theory for the capillary blood, Darcy flow for the porous media of the interstitium, a passive alveolus, and the Starling equation at both membranes. Case examples include normal physiology, cardiogenic pulmonary edema, acute respiratory distress syndrome (ARDS), hypoalbuminemia, and effects of PEEP. COVID-19 has dramatically increased ARDS in the world population, raising the urgency for such a model to create an analytical framework. Under normal conditions fluid exits the alveolus, crosses the interstitium, and enters the capillary. For edema, this crossflow is reversed with fluid leaving the capillary and entering the alveolus. Because both the interstitial and capillary pressures decrease downstream, the reversal can occur within a single septal tract, with edema upstream and clearance downstream. Clinically useful solution forms are provided allowing calculation of interstitial fluid pressure, crossflows, and critical capillary pressures. Overall, the interstitial pressures are found to be significantly more positive than values used in the traditional physiological literature. That creates steep gradients near the upstream and downstream end outlets, driving significant flows toward the distant lymphatics. This new physiological flow provides an explanation to the puzzle, noted since 1896, of how pulmonary lymphatics can function so far from the alveoli: the interstitium is self-clearing.

Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice.

Alport syndrome (AS), a type IV collagen disorder, leads to glomerular disease and, in some patients, hearing loss. AS is treated with inhibitors of the renin-angiotensin system; however, a need exists for novel therapies, especially those addressing both major pathologies. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist (DEARA) under clinical development for focal segmental glomerulosclerosis and IgA nephropathy. We report the ability of sparsentan to ameliorate both renal and inner ear pathologies in an autosomal-recessive Alport mouse model. Sparsentan significantly delayed onset of glomerulosclerosis, interstitial fibrosis, proteinuria, and glomerular filtration rate decline. Sparsentan attenuated glomerular basement membrane defects, blunted mesangial filopodial invasion into the glomerular capillaries, increased lifespan more than losartan, and lessened changes in profibrotic/pro-inflammatory gene pathways in both the glomerular and the renal cortical compartments. Notably, treatment with sparsentan, but not losartan, prevented accumulation of extracellular matrix in the strial capillary basement membranes in the inner ear and reduced susceptibility to hearing loss. Improvements in lifespan and in renal and strial pathology were observed even when sparsentan was initiated after development of renal pathologies. These findings suggest that sparsentan may address both renal and hearing pathologies in Alport syndrome patients. © 2023 Travere Therapeutics, Inc and The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Dynamic Regulation of Order Lipid Meso-domains in the Capillary Endothelial Cell Membrane

The structure and function of ion channels are sensitive to direct interactions with lipids of the membrane and to the biophysical properties of the membrane microenvironment, such that membrane fluidity, lateral pressure profile, and thickness can modulate the channels. Cholesterol plays a significant role in regulating membrane fluidity and is capable of phase separation where cholesterol will spontaneously separate into its own domain, which is partially responsible for developing two distinct domains within the membrane. These ordered domains are regions of high cholesterol and low fluidity, and the disordered domains are regions of low cholesterol and high fluidity. Here we examine and provide evidence of the presence of ordered cholesterol membrane domains in capillary endothelial cells. We will test the hypothesis that capillary endothelial cell ordered domains function as a signaling hub for different phospholipids regulating ion channel function. Using the isolated retinal vasculature, confocal microscopy, and fluorescent Bodipy-cholesterol, a marker of ordered lipid domains, we observed large regions approximately 2.3± 0.9 μm long of cholesterol ordered meso-domains within capillary endothelial cells and not the feeding arteriole. To determine the dynamic nature of these meso-domains, we used membrane-disordering drugs to disrupt the organization of membrane lipids. The ordered meso-domains display dynamic membrane disordering by ethanol and can re-cluster into the large ordered meso-domains. In addition, we observed that the critical signaling phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) co-localized with the ordered meso-domains. To determine the cooperativity between these lipid molecules, we examined the effects of ethanol-dependent disordering of cholesterol on the membrane localization of PIP2. In addition, we examined the effects of PIP2 depletion with the G-protein couple receptor agonist, U46619, on the disordered state of the cholesterol meso-domains. These data suggest that ordered meso-domains might play a role as a signaling hub affecting the membrane fluidity and bioavailability of signaling lipids modulating ion channel function in capillary endothelial cell. This is the full abstract presented at the American Physiology Summit 2023 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.

Can the response to dialysis treatment be predicted by using patient-specific modeling of fluid and solute exchanges? A multicentric evaluation.

Parametric multipool kinetic models were used to describe the intradialytic trends of electrolytes, breakdown products, and body fluids volumes during hemodialysis. Therapy customization can be achieved by the identification of parameters, allowing patient-specific modulation of mass and fluid balance across dialyzer, capillary, and cell membranes. This study wants to evaluate the possibility to use this approach to predict the patient's intradialytic response. 6 sessions of 68 patients (DialysIS© project) were considered. Data from the first three sessions were used to train the model, identifying the patient-specific parameters, that, together with the treatment settings and the patient's data at the session start, could be used for predicting the patient's specific time course of solutes and fluids along the sessions. Na+ , K+ , Cl- , Ca2+ , HCO3 - , and urea plasmatic concentrations and hematic volume deviations from clinical data were evaluated. nRMSE predictive error is on average equal to 4.76% when describing the training sessions, and only increases by 0.97 percentage points on average in independent sessions of the same patient. The proposed predictive approach represents a first step in the development of tools to support the clinician in tailoring the patient's prescription.

A rare case: negative-pressure pulmonary edema after routine rhinoplasty

Negative-pressure pulmonary edema (NPPE) is a very rare and dangeorus condition that generally occurs after general anesthesia in otorhinolaryngology practices. Post-obstructive pulmonary edema or NPPE caused by an acute pulmonary edema secondary to upper respiratory tract obstruction. Its sudden appearance in the early postoperative period can stress the surgeon and the anesthesiologist. Difficult breathing effort due to upper airway obstruction creates strong changes in intra-thoracic pressure, and high negative intrathoracic pressure increases the permeability of the alveolar capillary membrane, causing significant fluid changes in the pulmonary tissues. Treatment should be evaluated together with anesthesiologist or pulmonologist and the first goal should be to reduce the hypoxia.