A rabbit model of ear otitis established using the Malassezia pachydermatis strain C23 from dogs

Background and Aim: Fungal infections are a growing problem for both humans and animals due to the emergence of pathogenic strains resistant to modern antifungal treatments. To evaluate the efficacy of new antifungal drugs, it is essential to develop animal models that demonstrate typical responses to both the infection (pathogenesis and clinical course) and to the treatment, including adverse effects. In this study, we established a rabbit otitis model by infection of an aggressive multidrug-resistant strain from dogs, Malassezia pachydermatis C23, with no need for concomitant immunosuppression. Materials and Methods: Twenty healthy adult male gray giant rabbits (1 year old, 5.5 kg) were inoculated once with M. pachydermatis C23 at 108 colony-forming units/mL. We observed the clinical signs of the disease and collected ear smears and blood samples every 5 days. Results: The infection progressed rapidly and exhibited characteristic clinical signs without spontaneous recovery for at least 1 month. In fact, substantial deterioration was observed as evidenced by blood parameters. Conclusion: This rabbit otitis model established using an aggressive drug-resistant fungus strain without immunosuppression could prove valuable for testing novel antifungal agents

Патогенетические факторы, ассоциирующиеся с формированием острого абдоминального болевого синдрома собак при гастроэнтерите

Intercorrelative relationships between various clinical and laboratory parameters in dogs with acute gastroenteritis were studied. In dogs with acute alimentary gastroenteritis (n = 31), pain rating scale score significantly (p 0.05) correlated with pulse rate (r = 0.58), respiratory rate (r = 0.50), hematocrit (r = 0.47), ESR (r = 0.72), number of erythrocytes (r = 0.50) and leukocytes (r = 0.77), concentration of albumins (r = -0.52), globulins (r = 0.59), 1-globulins (r = 0.49), 2-globulins (r = 0.42), -globulins (r = -0.36), -globulins (r = 0.59), C-reactive protein (r = 0.82), serum activity of ALT (r = 0.70), AST (r = 0.39), -amylase (r = 0.38), alkaline phosphatase (r = 0.83) and serum concentration of creatinine (r = 0.42), tumor necrosis factor- (r = 0.82), interleukin-4 (r = 0.92), interleukin-6 (r = 0.92), interferon- (r = 0.91), interleukin-1 (r = 0.85), interleukin-8 (r = 0.91). The following changes were noted in the body of dogs with acute gastroenteritis: local and systemic immune-inflammatory response activated, pain, intoxication, dehydration syndrome, disorders of motor, secretory, absorption, excretory function of gastrointestinal tract formed, secondary hepatopathy and pancreatopathy developed. In dogs with acute gastroenteritis, there were also statistically significant (p 0.05) correlations between the number of erythrocytes and hematocrit (r = 0.65), MCHC (r = 0.32), ESR (r = 0.35), hemoglobin concentration (r = 0.73) and leukocyte count (r = 0.35); between MCV and hematocrit (r = 0.62), MCHC (r = -0.64); between MCV and MCHC (r = -0.64); MCH and MCHC (r = 0.40); ESR and leukocyte count (r = 0.53). Changes in intercorrelative relationships between clinical and laboratory parameters in dogs with acute gastroenteritis can be considered as predictors of severity of the pathological process.Исследовались интеркореллятивные связи между разнообразными клиническими и лабораторными показателями у собак, больных острым гастроэнтеритом. Показатель шкалы оценки боли достоверно (р ≤ 0,05) коррелировал с частотой пульса (r = 0,58), частотой дыхания (r  =  0,50), гематокритом (r = 0,47), СОЭ (r = 0,72), количеством эритроцитов (r = 0,50) и лейкоцитов (r = 0,77), концентрацией альбуминов в сыворотке крови (r = –0,52), глобулинов (r = 0,59), α1‑глобулинов (r = 0,49), α2‑глобулинов (r = 0,42), β-глобулинов (r = –0,36), γ-глобулинов (r = 0,59), С-реактивного белка (r = 0,82), сывороточной активностью аланиновой (r = 0,70) и аспарагиновой аминотрасфераз (r = 0,39), α-амилазы (r = 0,38), щелочной фосфатазы (r = 0,83) и сывороточной концентрацией креатинина (r = 0,42), фактора некроза опухоли-α (r = 0,82), интерлейкина‑4 (r = 0,92), интерлейкина‑6 (r = 0,92), интерферона-γ (r = 0,91), интерлейкина‑1α (r = 0,85), интерлейкина‑8 (r = 0,91). В организме собак, больных острым гастроэнтеритом, происходит активизация локальной и системной иммуновоспалительной реакции организма, возникает болевой, интоксикационный, дегидратационный синдром, происходят нарушения моторной, секреторной, всасывательной, экскреторной функции желудочно-­кишечного тракта, формируется вторичная гепатопатия и панкреатопатия. Также констатировано наличие статистически значимых (р ≤ 0,05) коррелятивных связей между количеством эритроцитов и показателем гематокрита (r = 0,65), MCHC (r = 0,32), СОЭ (r = 0,35), концентрацией гемоглобина (r = 0,73) и количеством лейкоцитов (r = 0,35); между MCV и гематокритом (r = 0,62), MCHC (r = –0,64); между MCV и MCHC (r = 0,64); MCH и MCHC (r = 0,40); СОЭ и количеством лейкоцитов (r = 0,53). Изменения интеркоррелятивных связей между клинико-­лабораторными параметрами у больных острым гастроэнтеритом собак можно рассматривать как предикторы тяжести патологического процесса

Advances in Nrf2 Signaling Pathway by Targeted Nanostructured-Based Drug Delivery Systems

Nanotechnology has gained significant interest in various applications, including sensors and therapeutic agents for targeted disease sites. Several pathological consequences, including cancer, Alzheimer’s disease, autoimmune diseases, and many others, are mostly driven by inflammation and Nrf2, and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), plays a crucial role in maintaining redox status, the expression of antioxidant genes, and the inflammatory response. Interestingly, tuning the Nrf2/antioxidant response element (ARE) system can affect immune–metabolic mechanisms. Although many phytochemicals and synthetic drugs exhibited potential therapeutic activities, poor aqueous solubility, low bioavailability, poor tissue penetration, and, consequently, poor specific drug targeting, limit their practical use in clinical applications. Also, the therapeutic use of Nrf2 modulators is hampered in clinical applications by the absence of efficient formulation techniques. Therefore, we should explore the engineering of nanotechnology to modulate the inflammatory response via the Nrf2 signaling pathway. This review will initially examine the role of the Nrf2 signaling pathway in inflammation and oxidative stress-related pathologies. Subsequently, we will also review how custom-designed nanoscale materials encapsulating the Nrf2 activators can interact with biological systems and how this interaction can impact the Nrf2 signaling pathway and its potential outcomes, emphasizing inflammation

Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies

Expandable metallic stent placement is often the only way to treat airway obstructions. Such treatment with an uncoated stent causes granulation proliferation and subsequent restenosis, resulting in the procedure’s adverse complications. Systemic administration of steroids drugs in high dosages slows down granulation tissue overgrowth but leads to long-term side effects. Drug-eluting coatings have been used widely in cardiology for many years to suppress local granulation and reduce the organism’s systemic load. Still, so far, there are no available analogs for the trachea. Here, we demonstrate that PLA-, PCL- and PLGA-based films with arrays of microchambers to accommodate therapeutic substances can be used as a drug-eluting coating through securely fixing on the surface of an expandable nitinol stent. PCL and PLA were most resistant to mechanical damage associated with packing in delivery devices and making it possible to keep high-molecular-weight cargo. Low-molecular-weight methylprednisolone sodium succinate is poorly retained in PCL- and PLGA-based microchambers after immersion in deionized water (only 9.5% and 15.7% are left, respectively). In comparison, PLA-based microchambers retain 96.3% after the same procedure. In vivo studies on rabbits have shown that effective granulation tissue suppression is achieved when PLA and PLGA are used for coatings. PLGA-based microchamber coating almost completely degrades in 10 days in the trachea, while PLA-based microchamber films partially preserve their structure. The PCL-based film coating is most stable over time, which probably causes blocking the outflow of fluid from the tracheal mucosa and the aggravation of the inflammatory process against the background of low drug concentration. Combination and variability of polymers in the fabrication of films with microchambers to retain therapeutic compounds are suggested as a novel type of drug-eluting coating