Contralateral sialadenitis after resection of a right cerebellar metastasis: illustrative case

BACKGROUND Acute postoperative sialadenitis is a rare and potentially morbid complication of cranial neurosurgery. This rapidly progressive, unilateral neck swelling often presents within hours of extubation. Diagnosis is made by imaging and exclusion of other causes of etiologies, such as neck hematoma, sialolithiasis, and dependent soft tissue edema. OBSERVATIONS The authors presented a case of acute postoperative sialadenitis after suboccipital resection of a right cerebellar metastasis. Shortly after extubation, extensive left-sided neck swelling was apparent in the postanesthesia care unit. No central lines were placed during the procedure. Imaging revealed submandibular gland edema and fluid accumulation in the surrounding tissue. The patient was managed conservatively with steroids, antibiotics, and warm compresses, with complete resolution of symptoms 2 weeks after the procedure. LESSONS This case emphasizes the broad differential of acute neck swelling after cranial surgery. Physical examination of the neck and airway protection should guide initial treatment. If a patient is stable, bedside ultrasound and computed tomography can be helpful with the differential diagnosis. Here the authors proposed an algorithm for diagnosis and treatment of acute neck swelling after cranial surgery.

Modulation of oxidative and nitrosative stress attenuates microvascular hyperpermeability in ovine model of Pseudomonas aeruginosa sepsis

In sepsis, microvascular hyperpermeability caused by oxidative/nitrosative stress (O&NS) plays an important role in tissue edema leading to multi-organ dysfunctions and increased mortality. We hypothesized that a novel compound R-107, a modulator of O&NS, effectively ameliorates the severity of microvascular hyperpermeability and preserves multi-organ function in ovine sepsis model. Sepsis was induced in twenty-two adult female Merino sheep by intravenous infusion of Pseudomonas aeruginosa (PA) (1 × 1010 CFUs). The animals were allocated into: 1) Control (n = 13): intramuscular injection (IM) of saline; and 2) Treatment (n = 9): IM of 50 mg/kg R-107. The treatment was given after the PA injection, and monitored for 24-h. R-107 treatment significantly reduced fluid requirement (15–24 h, P < 0.05), net fluid balance (9–24 h, P < 0.05), and water content in lung/heart/kidney (P = 0.02/0.04/0.01) compared to control. R-107 treatment significantly decreased lung injury score/modified sheep SOFA score at 24-h (P = 0.01/0.04), significantly lowered arterial lactate (21–24 h, P < 0.05), shed syndecan-1 (3–6 h, P < 0.05), interleukin-6 (6–12 h, P < 0.05) levels in plasma, and significantly attenuated lung tissue 3-nitrotyrosine and vascular endothelial growth factor-A expressions (P = 0.03/0.002) compared to control. There was no adverse effect in R-107 treatment. In conclusion, modulation of O&NS by R-107 reduced hyperpermeability markers and improved multi-organ function.

Anticoagulation Targeting Membrane-Bound Anionic Phospholipids Improved Outcomes of Traumatic Brain Injury in Mice

Severe traumatic brain injury (TBI) often causes an acute systemic hypercoagulable state that rapidly develops into consumptive coagulopathy. We have recently demonstrated that TBI-induced coagulopathy (TBI-IC) is initiated and disseminated by brain-derived extracellular vesicles (BDEVs) and propagated by extracellular vesicles (EVs) from endothelial cells and platelets. Here, we present results from a study designed to test the hypothesis that anticoagulation targeting anionic phospholipid-expressing EVs prevents TBI-IC and improves the outcomes of mice subjected to severe TBI. We evaluated the effects of a fusion protein (ANV-6L15) for improving the outcomes of TBI. ANV-6L15 combines the phosphatidylserine (PS)-binding annexin V with a peptide anticoagulant modified to preferentially target extrinsic coagulation. We found that ANV-6L15 reduced intracranial hematoma by 70.2%, improved neurological function, and reduced death by 56.8% in mice subjected to fluid percussion injury at 1.9 atm. It protected the TBI mice by preventing vascular leakage, tissue edema, and the TBI-induced hypercoagulable state. We further showed that the extrinsic tenase complex was formed on the surfaces of circulating EVs, with the highest level found on BDEVs. Phospholipidomic analysis detected the highest levels of PS on BDEVs, as compared to EVs from endothelial cells and platelets (79.1, 15.2, and 3.5 nM/mg of protein, respectively). These findings demonstrate that TBI-IC results from a trauma-induced hypercoagulable state and may be treated by anticoagulation targeting on the anionic phospholipid-expressing membrane of EVs from the brain and other cells.

Modulation of Oxidative and Nitrosative Stress Attenuates Microvascular Hyperpermeability in Ovine Model of Pseudomonas Aeruginosa Sepsis

In sepsis, microvascular hyperpermeability caused by oxidative/nitrosative stress (O&NS) plays an important role in tissue edema leading to multi-organ dysfunctions and increased mortality. We hypothesized that a novel compound R-107, a modulator of O&NS, effectively ameliorates the severity of microvascular hyperpermeability and preserves multi-organ function in ovine sepsis model. Sepsis was induced in twenty-two adult female Merino sheep by intravenous infusion of Pseudomonas aeruginosa (PA) (1x1010 CFUs). The animals were allocated into: 1) Control (n = 13): intramuscular injection (IM) of saline; and 2) Treatment (n = 9): IM of 50 mg/kg R-107. The treatment was given after the PA injection, and monitored for 24-hour. R-107 treatment significantly reduced fluid requirement (15–24 hours, p < 0.05), net fluid balance (9–24 hours, p < 0.05), and water content in lung/heart/kidney (p = 0.02/0.04/0.01) compared to control. R-107 treatment significantly decreased lung injury score/modified sheep SOFA score at 24-hour (p = 0.01/0.04), significantly lowered arterial lactate (21–24 hours, p < 0.05), shed syndecan-1 (3–6 hours, p < 0.05), interleukin-6 (6–12 hours, p < 0.05) levels in plasma, and significantly attenuated lung tissue 3-nitrotyrosine and vascular endothelial growth factor-A expressions (p = 0.03/0.002) compared to control. There was no adverse effect in R-107 treatment. In conclusion, modulation of O&NS by R-107 reduced hyperpermeability markers and improved multi-organ function.

Engineering a whole rat liver scaffold

Engineering a three-dimensional scaffold opens up great prospects for creation of manufacturing biological artificial organs. The article presents a method of perfusion decellularization of a rat liver, with the main problems and options for their solution being analyzed. Perfusion of a donor liver with 0.1 % a sodium dodecyl sulfate (SDS) solution allows obtaining a high-quality cell-free matrix characterized by preserved hepatic architectonics, patent vascular bed, residual DNA of less than 1 %, no signs of collagen fibers destruction and tissue edema. The obtained scaffold can be used for recellularization by allogeneic cell cultures when creating volumetric tissue-engineered designs.

RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25-mediated K63-linked polyubiquitination

Upon viral RNA recognition, the RIG-I signalosome continuously generates IFNs and cytokines, leading to neutrophil recruitment and inflammation. Thus, attenuation of excessive immune and inflammatory responses is crucial to restore immune homeostasis and prevent unwarranted damage, yet few resolving mediators have been identified. In the present study, we demonstrated that RTN3 is strongly upregulated during RNA viral infection and acts as an inflammation-resolving regulator. Increased RTN3 aggregates on the endoplasmic reticulum and interacts with both TRIM25 and RIG-I, subsequently impairing K63-linked polyubiquitination and resulting in both IRF3 and NF-κB inhibition. Rtn3 overexpression in mice causes an obvious inflammation resolving phenomenon when challenged with VSV, Rtn3-overexpressing mice display significantly decreased neutrophil numbers and inflammatory cell infiltration, which is accompanied by reduced tissue edema in the liver and thinner alveolar interstitium. Taken together, our findings identify RTN3 as a conserved negative regulator of immune and inflammatory responses and provide insights into the negative feedback that maintains immune and inflammatory homeostasis.

Biopharmaceutical and rheometric studies in the development of a gel composition with dimethindene maleate

Every year there is an increase in the number of cases of hypersensitivity to bites from various insects. A local allergic reaction to bites occurs within a few minutes and is accompanied by acute pain at the site of the bite, severe itching, hyperemia, the appearance of papules, tissue edema, and sometimes a small-point rash around. Considering the small number of drugs for local therapy of allergic manifestations and the unidirectional nature of their action, it is urgent to develop a drug containing the antihistamine dimethindene maleate and dexpanthenol, which plays the role of an anti-inflammatory, reparative and dermatoprotective substance. The aim. The aim of the study is to substantiate the delivery system of dimethindene maleate and dexpanthenol based on biopharmaceutical and rheometric research methods. Materials and methods. To determine the component composition of the active ingredient delivery system, the type of dimetindene maleate administration was substantiated by studying its solubility. As a delivery system for active pharmaceutical ingredients, hydrogels were considered, which were made using high-molecular compounds of various origins: a natural substance – xanthan gum, a semi-synthetic substance – gyroxypropyl methylcellulose, and a synthetic substance – carbomer. The rate of release of dimethindene maleate from hydrogels was estimated by studying the kinetics of release through a semipermeable membrane. The assessment of the viscoelastic properties of hydrogels was carried out by performing an oscillatory rheometry test, which makes it possible to quantitatively determine the viscous and elastic components, as well as to characterize the bioadhesive properties. Results. Based on the results of studying the solubility of dimethindene maleate in hydrophilic non-aqueous solvents, it was determined that propylene glycol is optimal for ensuring the introduction of a substance into hydrogel bases as a solution. As a result of studying the kinetics of the release of dimethindene maleate from hydrogels, it was found that the use of carbomer as a delivery system provides the release of 28.33 % of dimethindene maleate, xanthan gum – 25 %, hydroxypropyl methylcellulose – 7.33 %. When studying the viscoelastic properties by determining the values ​​of the storage modulus G', the loss modulus G" and the damping (attenuation) factor tg δ, it was found that the carbomer-based hydrogel is a viscoelastic solid, the xanthan gum and hydroxypropyl methylcellulose-based hydrogels are a viscoelastic liquid. Bioadhesion on the surface of the skin during use has the advantage of carbomer hydrogel. Conclusions. Based on the combination of biopharmaceutical and rheometric methods for substantiating the composition of the delivery system for dimetindene maleate and dexpanthenol, it is rational to use carbomer for further pharmacological and microbiological studies