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The synthesized compound, 1-(2-ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl propionate (EPPP), and its 1:1 complex with β-cyclodextrin (EPPPβCD) have been characterized for the first time through a comprehensive suite of analytical methods. This study explores the therapeutic potential of EPPPβCD in modulating immune responses and accelerating the resolution of septic inflammation induced by chromium and vanadium ions in outbred male rats. The research highlights the significant impact of EPPPβCD on the dynamics of regulatory T lymphocytes (Tregs), notably causing a reduction in the CD4+CD25+ fractions at the onset of inflammation. This effect is attributed to the inhibition of Treg proliferation, which is crucial in hastening the resolution of inflammation. These findings underscore the potential of EPPPβCD as a promising therapeutic agent in controlling and mitigating inflammation mediated by heavy metal exposure, thereby offering a new avenue for the development of anti-inflammatory treatments. [ABSTRACT FROM AUTHOR]

One of the important problems of medicine is the search for new reliable markers of inflammation that would allow us to determine the type of inflammatory process. The aim of the study was to identify specific markers of infectious and aseptic inflammation based on the analysis of morphological variants of neutrophil extracellular traps (NETs). The study included 26 patients with various nosological forms of inflammation in the abdominal cavity (12 with acute appendicitis, 8 with acute cholecystitis, 6 with a diagnosis of pancreatitis/ pancreonecrosis) after surgery. The study also included 20 patients with post-COVID and a group of 10 volunteers no clinical manifestations of the disease, but at the same time had contacts with flu patients. Neutrophils were isolated using gradient centrifugation. Fluorescence microscopies with the dye SYBR Green (JSC “Evrogen”, Russia) were used for NET visualization and counting. NETs in the morphological form of neutrophils web structure were found in the blood of surgical patients with acute appendicitis who had a favorable course of the postoperative period. In a group of volunteers who were exposed to influenza but did not have symptoms of an infectious disease, we also found neutrophils web structure. In all patients with abdominal inflammation complicated by abdominal abscess, in addition to neutrophil web structure, abnormal forms of NETs were recorded, in particular, NETs in the form of single filaments. In the post-COVID patients an absolute absence of neutrophilis web structure was revealed. In all post-COVID patients, NETs are found only in the form of single filaments. The results of subsequent experiments showed that collagen peptides are inducers of the formation of NETs in the form of single filaments. The detection of neutrophils web structure is a sign of an infectious inflammatory process. NETs in the morphological form of single filaments are markers of aseptic inflammation, as well as a sign of endothelial damage.

Ischemic heart disease (IHD) can trigger responses from the innate immune system, provoke aseptic inflammatory processes, and result in the recruitment and accumulation of neutrophils. Excessive recruitment of neutrophils is a potential driver of persistent cardiac inflammation. Once recruited, neutrophils are capable of secreting a plethora of inflammatory and chemotactic agents that intensify the inflammatory cascade. Additionally, neutrophils may obstruct microvasculature within the inflamed region, further augmenting myocardial injury in the context of IHD. Immune-related molecules mediate the recruitment process of neutrophils, such as immune receptors and ligands, immune active molecules, and immunocytes. Non-immune-related molecular pathways represented by pro-resolving lipid mediators are also involved in the regulation of NR. Finally, we discuss novel regulating strategies, including targeted intervention, agents, and phytochemical strategies. This review describes in as much detail as possible the upstream molecular mechanism and external intervention strategies for regulating NR, which represents a promising therapeutic avenue for IHD. [ABSTRACT FROM AUTHOR]

Abstract Background In this retrospective review, the relative importance of systemic inflammation among other causes of acute kidney injury (AKI) was investigated in 1224 consecutive colorectal surgery patients. A potential benefit from reducing excessive postoperative inflammation on AKI might then be estimated. Methods AKI was determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The entire population (mixed group), composed of patients with or without sepsis, and a subpopulation of patients without sepsis (aseptic group) were examined. Markers indicative of inflammation were procedure duration, the first postoperative white blood cell (POD # 1 WBC) for the mixed population, and the neutrophil-to-lymphocyte ratio (POD #1 NLR) for the aseptic population. Multivariable logistic regression was then performed using significant (P

Background: In this retrospective review, the relative importance of systemic inflammation among other causes of acute kidney injury (AKI) was investigated in 1224 consecutive colorectal surgery patients. A potential benefit from reducing excessive postoperative inflammation on AKI might then be estimated. Methods: AKI was determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The entire population (mixed group), composed of patients with or without sepsis, and a subpopulation of patients without sepsis (aseptic group) were examined. Markers indicative of inflammation were procedure duration, the first postoperative white blood cell (POD # 1 WBC) for the mixed population, and the neutrophil-to-lymphocyte ratio (POD #1 NLR) for the aseptic population. Multivariable logistic regression was then performed using significant (P < 0.05) predictors. The importance of inflammation among independent predictors of AKI and AKI-related complications was then assessed. Results: AKI occurred in 24.6% of the total population. For the mixed population, there was a link between inflammation (POD # 1 WBC) and AKI (P = 0.0001), on univariate regression. Medications with anti-inflammatory properties reduced AKI: ketorolac (P = 0.047) and steroids (P = 0.038). Similarly, in an aseptic population, inflammation (POD # 1 NLR) contributed significantly to AKI (P = 0.000). On multivariable analysis for the mixed and aseptic population, the POD #1 WBC and the POD #1 NLR were independently associated with AKI (P = 0.000, P = 0.022), as was procedure duration (P < 0.0001, P < 0.0001). Inflammation-related parameters were the most significant contributors to AKI. AKI correlated with complications: postoperative infections (P = 0.016), chronic renal insufficiency (CRI, P < 0.0001), non-infectious complications (P = 0.010), 30-day readmissions (P = 0.001), and length of stay (LOS, P < 0.0001). Inflammation, in patients with or without sepsis, was similarly a predictor of complications: postoperative infections (P = 0.002, P = 0.008), in-hospital complications (P = 0.000, P = 0.002), 30-day readmissions (P = 0.012, P = 0.371), and LOS (P < 0.0001, P = 0.006), respectively. Conclusions: Systemic inflammation is an important cause of AKI. Limiting early postsurgical inflammation has the potential to improve postoperative outcomes. [ABSTRACT FROM AUTHOR]

The treatment of aseptic inflammation has always been a clinical challenge. At present, non-steroidal drug-loaded microspheres have been widely used in the treatment of aseptic inflammation due to their excellent injectable and sustained release capabilities. In this study, ketoprofen-loaded shellac microspheres (Keto-SLAC) were prepared by electrospray. Alterations of Keto-SLAC morphology was observed in response to changed shellac concentration in ethanol solution through electrospray. Further examination revealed that ketoprofen presented as amorphous solid dispersion in the shellac microspheres. Most importantly, it was also shown that ketoprofen can be slowly released from the shellac matrix for up to 3 weeks. In vitro cell experiments verified that the microspheres had favorable cell compatibility. We therefore proposed that the prepared microspheres, being readily available in use in a variety of clinical settings through topical application, have promising therapeutic potential for the treatment of aseptic inflammation.

The synthesized compound, 1-(2-ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl propionate (EPPP), and its 1:1 complex with β-cyclodextrin (EPPPβCD) have been characterized for the first time through a comprehensive suite of analytical methods. This study explores the therapeutic potential of EPPPβCD in modulating immune responses and accelerating the resolution of septic inflammation induced by chromium and vanadium ions in outbred male rats. The research highlights the significant impact of EPPPβCD on the dynamics of regulatory T lymphocytes (Tregs), notably causing a reduction in the CD4+CD25+ fractions at the onset of inflammation. This effect is attributed to the inhibition of Treg proliferation, which is crucial in hastening the resolution of inflammation. These findings underscore the potential of EPPPβCD as a promising therapeutic agent in controlling and mitigating inflammation mediated by heavy metal exposure, thereby offering a new avenue for the development of anti-inflammatory treatments.

Background: The greater omentum of white rats appears, in basic morphological features (in miniature), to be homologous to the greater omentum of humans. We study of the greater omentum reaction to the catgut implant. After implantation of the catgut thread, it turned out that not only the greater omentum, but also serous formations similar to it, related to the testicles, are involved in the covering of the implant. The aim of the study was to study the general plan of the structure and the principles of morphometric analysis of serous formations of testis in white male rats.Materials and Methods: The experiment involved 15 white male rats of reproductive age, weighing from 284 to 334 grams.Results: It has been established that each testicle of white rats has serous (peritoneal derivatives) formations of two types. One of them is a typical mesentery, with which each testicle is separately fixed to the posterior wall of the pelvic cavity, and the other formation is a free regrowth of a duplication of the serous membrane. It was called the epididymal omentum. According to the algorithm for studying the greater omentum in our previous works, it is noteworthy that the area of ​​the greater omentum is noticeably inferior to the area of ​​the epididymal omentums (F=0.239; p=0.006). So, if the average value of the area of ​​the greater omentum is 2766.51±388.12mm², then the same indicator of the epididymal omentum reaches 4383.36±793.56 mm², with their approximately the same thickness (F=1.35; p=0.291).Conclusions: It has been established that the greater omentum has two, homeomorphic to it, derivatives of the peritoneum, associated with the epididymis, which were justifiably called epididymal omentums and were fully described in the literature for the first time. [ABSTRACT FROM AUTHOR]

Suture material used in abdominal surgery must have more or less antigenic properties so that during wound healing it could be destroyed by an immune response to rejection, which is known to involve cytotoxic T-lymphocytes and macrophages. This, in turn, can lead to the development of aseptic peritonitis. Therefore, while planning an experimental simulation of aseptic peritonitis, we decided to use catgut thread as an antigenic stimulation of the local immune system. The aim of our research was to study the morphological criteria of the microscopic structure and tinctorial properties of catgut thread. The material of the research was the sterile catgut thread sized 2/0, 0.3 mm thick, of equal lengths, which we twisted arbitrarily into flat compact globules occupying an area of approximately 1 cm2. In order to carry out a histological examination, some catgut globules were subjected to total staining with a hematoxylineosin solution and subsequent embedding of these globules in a paraffin block and making appropriate sections from it. The other half of the catgut globules were studied using the method of epoxy plastination with the production of grinds with staining by a 1% solution of methylene blue on a 1% borax and without any staining. After the total staining of the catgut globules with a hematoxylin-eosin solution, a clear acidophilic reaction was revealed, which was manifested in the intense pink color. Catgut thread has a non-uniform fibrous structure, in which dark streaks stand out, dividing it into a series of longitudinal, lighter, layered fascicles, which consist of a dense collection of thin fibrillar elements. These fibrillar elements are orderly fascicles of collagen fibers, while the dark streaks are layers of loose fibrous connective tissue. These structures can objectively be indicative of morphological criteria in the microscopic analysis of destructive changes of a catgut implant in the peritoneal cavity in an experimental animal.

Abstract Background Postoperative fever is one of the common complications in neurosurgery, and intracranial aseptic inflammation and infection are important risk factors. Continuous drainage of cerebrospinal fluid (CSF) via lumbar drainage (LD) is often used in the treatment of postoperative intracranial infection or aseptic inflammation. Compared with the previously reported placement of LD after the onset of meningitis symptoms, we designed this randomized controlled trial (RCT) to evaluate the effectiveness and safety of early drainage (1st day postoperation) of CSF using the preset lumbar cistern to prevent delayed fever (fever occurred after the third day postoperation) or reduce its treatment time after cerebellopontine angle (CPA) tumour surgery. Methods Patients suffering from CPA tumours and who underwent resection of the tumour with an intraoperative dura opening time > 4 h are recruited for this study. The study is a 2-arm RCT to compare the early LD group and the no early LD group. Postoperative duration and rate of delayed fever and postoperative length of stay (LOS), as the main outcomes, will be compared in the two groups. Discussion Here, we present the study design of a prospective RCT to evaluate the safety and efficacy of using preoperative preset LD to treat or reduce postoperative delayed fever. Trial registration China Clinical Trial Registry ChiCTR2100049057. Registered on July 20, 2021.

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot foot) is a relatively rare complication of diabetes mellitus (DM), which can lead not only to impaired support function of the lower limb in such patients, but also to high amputation. DNOAP is characterized by persistent aseptic inflammation of the bone structures of the foot, which creates significant ­difficulties in planning therapeutic measures. In the medical literature, there are data demonstrating the role of individual ­cytokines and neurohumoral factors in the prolongation of the inflammatory process in diabetes, however, there are currently very few studies that determine reliable markers of aseptic inflammation in DNOAP.AIM: To study the effect of neurohumoral factors and advanced glycation end products on the activity of aseptic inflammation in the bone structures of the foot in patients with type 2 diabetes mellitus (DM2) and diabetic neuroosteoarthropathy.MATERIALS AND METHODS. The study included 88 patients with type 2 diabetes (45 men, 43 women). Group 1 consisted of patients with DM2 and inactive DNOAP (n= 43), group 2 (n= 45) consisted of patients with DM2 and distal diabetic neuropathy without osteoarticular pathology. The diagnosis of diabetic neuropathy was based on the analysis of the clinical picture and indicators of peripheral sensitivity. Diagnosis of DNOAP and determination of its stage was based on clinical data, the results of infrared thermometry and radiology tests of the foot bones. General clinical assessment was used, radiology tests (X-ray, MRI), evaluation of CRP, calprotectin, copeptin, glutathione peroxidase 1 (GP1).RESULTS. According to the results of examination and palpation of the feet, as well as the analysis of the temperature gradient of the skin of the affected and contralateral limb (infrared thermometry), DNOAP was detected and the stage of this complication was determined. The diagnosis of the chronic stage of DNOAP was confirmed by the results of MRI and the clinical picture (no difference in skin temperature on the symmetrical areas of the feet). According to the results of laboratory analysis, a statistically significant difference in copeptin values was revealed — in group 1 — 0.232 µg/ml [0.147; 0.342], in group 2 — 0.115 µg/ml [0.065; 0.203] (p>0.05) and CRP — in group 1 — 7.113 mg/l [2.453; 16.505], in group 2 — 2.187 mg/l [1.131; 5.567] (p>0.05), leukocyte levels in the groups did not differ significantly: group 1 — 7.86 [6.40; 9.00]*10^9, group 2 — 7.00 [6.00; 8.15] (p>0.05). There was a trend towards an increase in the level of calprotectin and glutathione peroxidase-1 in the DNOAP group, however, the differences were not significant. calprotectin — in group 1 — 1.948 [1.229; 2.969], in group 2 — 1.692 [1.16; 2.514] μg/ml and glutathione peroxidase-1 in group 1 — 24.72 [20.1; 31.82], in group 2 — 22.98 [18.94; 31.2] ng/ml.CONCLUSION. In the study, statistically significant differences were obtained in the levels of copeptin and C-reactive protein: in patients with DNOAP, their values were significantly higher, which indicates the persistence of the aseptic inflammatory process in the bone tissue of patients even in the chronic stage of DNOAP. These data may help in deciding whether to use one or another method of unloading the affected joints, which will affect the clinical prognosis. The study of neurohumoral markers of arthropathy in the blood serum of patients with DM2 is carried out for the first time, and therefore it is difficult to compare with the results of other authors. It can be assumed that copeptin and CRP are significant markers of persistent inflammation of the osteoarticular structures of the foot in DNOAP.

Background: Postoperative fever is one of the common complications in neurosurgery, and intracranial aseptic inflammation and infection are important risk factors. Continuous drainage of cerebrospinal fluid (CSF) via lumbar drainage (LD) is often used in the treatment of postoperative intracranial infection or aseptic inflammation. Compared with the previously reported placement of LD after the onset of meningitis symptoms, we designed this randomized controlled trial (RCT) to evaluate the effectiveness and safety of early drainage (1st day postoperation) of CSF using the preset lumbar cistern to prevent delayed fever (fever occurred after the third day postoperation) or reduce its treatment time after cerebellopontine angle (CPA) tumour surgery. Methods: Patients suffering from CPA tumours and who underwent resection of the tumour with an intraoperative dura opening time > 4 h are recruited for this study. The study is a 2-arm RCT to compare the early LD group and the no early LD group. Postoperative duration and rate of delayed fever and postoperative length of stay (LOS), as the main outcomes, will be compared in the two groups. Discussion: Here, we present the study design of a prospective RCT to evaluate the safety and efficacy of using preoperative preset LD to treat or reduce postoperative delayed fever. Trial registration: China Clinical Trial Registry ChiCTR2100049057. Registered on July 20, 2021. [ABSTRACT FROM AUTHOR]

– Despite the guidance of aseptic technology applied, bacterial meningitis seems to be an unavoidable obstacle in the process of neurosurgery, with high rates of disability and mortality. The diagnosis of post-neurosurgical bacterial meningitis (PNBM) mainly depends both on clinical symptoms and laboratory outcomes. Due to the excessive neuro-inflammatory reactions which are evoked by the primary brain disease or the craniotomy operation, the symptoms derived from the infection and aseptic may not be easily distinguished. On the other hand, the low positive rate and time-consuming character restrict the clinical practical values of bacterial culture. Therefore, it is always difficult to make a definite diagnosis of post-neurosurgical bacterial meningitis. Here, we reviewed the established literature about the diagnostic biomarkers for the PNBM and analyzed the potential obstacles in both clinical and scientific studies. Given the obstacle which has negative impacts on further investigation about the biology of PNBM, we only find relatively small numbers of study on PNBM. In this review, we summarize the established diagnostic methods and biomarkers for PNBM. Meanwhile, we also propose some potential investigation prospects. This review may help to better understand the character of PNBM in both clinical diagnosis and scientific investigations. [ABSTRACT FROM AUTHOR]

Objective To investigate the etiology, diagnosis and treatment of granulomatous cheilitis（GC）. Methods For a patient with recurrent granulomatous cheilitis for more than 1 year in whom no medical treatment was used, only systemic treatment of the teeth was performed, and its efficacy was observed. We also reviewed the relevant literature. Results The vermilion of the right lower lip of the patient was obviously swollen and soft. There was rebound and no pitting edema with palpation. A large dark red rash with local desquamation was observed on the skin over the right mandible. There were residual roots in tooth 35, 46, and 47, a porcelain bridge on 11-24, deep caries in 15, 16, 26, and 36, and many calculi in the whole mouth, and the gingival margin was obviously congested and swollen. Histopathological examination showed many lymphocytes infiltrated the superficial dermis, and granulation tissue, plasma cells and eosinophils infiltrated locally. The diagnosis was as follows: ① GC; ② 35, 46, and 47 residual roots; ③ 15, 16, 26, and 36 deep caries; ④ gingivitis. The treatment included extraction of 35, 46, and 47 residual roots, periodontal basic treatment, and fillings for 15, 16, 26, and 36. No drugs were administered except for 3 days after tooth extraction. After 5 weeks of treatment, the swelling of the lower lip and the skin rash completely disappeared. There was no recurrence in the follow-up observation at six months. Through a literature review and analysis, we found that GC may be related to various factors such as immunity, infection, and genetics. Local oral infections may be closely related to the incidence of GC. Conclusion Resolution of local oral infections is effective for the treatment of granulomatous cheilitis, and local oral infections may be closely related to the onset of granulomatous cheilitis. In the treatment of granulomatous cheilitis, attention should be paid to the systematic examination of the oral condition, and the treatment of suspected lesions in the oral cavity should begin in the early stages of treatment.

Background. Familial Mediterranean fever (FMF) is the brightest exponent of autoinflammatory diseases. FMF usually occurs to people of Mediterranean origin (Jews, Armenians, Azerbaijanis, Arabs, Kurds, Greeks, Turks and Italians). This is a hereditary disease with the autosomal recessive inheritance. Includes history of research, epidemiology FMF, variants of the disease course, methods of treatment. Clinical case description. A 61-year-old woman arrived complaining of weakness, fever, joint pain. First sign of disease showed at 20-years-old. When she came in: WBC 20.1109/l, HGB 6.7 g/ml, ESR 60 mm/h, CRP 100 mg/l, CRP 202 mol/L, UREA 19.7 mmol/L. Quantity of protein in one liter of urine 0.160 g. Ultrasonic signs of pyelectasis in both kidneys. The diagnosis was made on the basis of characteristic attacks of fever, polyarthritis, thoracalgia of Armenian nationality patient. The diagnosis was confirmed by the detection of amyloidosis and genetic data. Conclusion. Knowledge of the FMF clinical profile is important for differential diagnosis with many acute conditions, e.g. acute abdomen, myocardial infarction, pneumothorax, rheumatic diseases. It is important to remember that untimely diagnosis and improper treatment lead to the development of AA-amyloidosis (3040%) with the outcome of renal failure.

Heavy metal pollution is rapidly increasing in the environment. It has been shown that exposure to vanadium and chromium is able to alter the immune response. Nevertheless, the mechanisms by which these metal pollutants mediate their immunomodulatory effects are not completely understood. Herein, we examined the effect of ammonium metavanadate and potassium dichromate on the development of an inflammatory response caused by subcutaneous injection of turpentine oil. We demonstrated that pretreatment of rats with ammonium metavanadate and potassium dichromate for two weeks prior to initiation of the inflammatory response resulted in a wider zone of necrosis surrounding the site of inflammation. The acute inflammatory process in the combined model was characterized by elevated serum levels of IL-10 and decreased serum levels of IL-6 as compared to rats not treated with ammonium metavanadate and potassium dichromate. Ammonium metavanadate and potassium dichromate administration induced a decrease in the proportion of splenic His48HighCD11b/c+ myeloid cells accompanied by a reduced infiltration of the wound with neutrophils. Further analysis showed decreased proportions of CD3+CD4+IFNγ+ and CD3+CD4+IL-4+ T cells in the rats with combined model as compared to inflamed rats not treated with ammonium metavanadate and potassium dichromate. The data suggest that consumption of vanadium and chromium compounds disrupts the inflammatory response through an altered balance of pro- and anti-inflammatory cytokines and inhibition of effector T cell activation and neutrophil expansion. [ABSTRACT FROM AUTHOR]

Background. Treatment of joint pathology, both degenerative and traumatic, is a long, multicomponent process that requires joint efforts of the doctor and the patient. The choice of the optimal therapy is complex and ambiguous. Biologically active compounds are one of the most powerful things for fighting with inflammatory process, which is a constant companion of damage. Due to their antioxidant, immunomodulatory and regenerative properties, placental fragments were admitted as a perspective treatment for arthropathies of various etiologies. Purpose of the research: to determine the morphological characteristics of the constituent structures of the knee joints of rats in a comparative aspect under normal conditions, in experimental arthritis and after exposure to a cryopreserved placenta. Material and methods. An experimental study was carried out on 115 white rats. With the intact group (10 animals) we compared 3 control groups of 35 animals each, who underwent: 1) modeling of carrageenan-induced aseptic inflammation of the knee joint; 2) subcutaneous implantation of placental fragment; 3) subcutaneous implantation of placental fragment against the background of aseptic inflammation of the knee joint. Histological preparations were prepared according to the general methods with hematoxylin-eosin and Van Gieson staining. Results. During the creating an inflammatory focus, changes in the cartilaginous tissue were determined from day 3 in the form of lacunarity, karyopyknosis as a stage of necrobiosis of chondrocytes, especially pronounced on days 10–14. Morphological changes in the bone tissue of rats, which were injected λ-carrageenan, were noted on the 7th day of the research in the form of resorption and destruction of bone trabeculae. Later (day 10), the inflammatory process led to a picture of the fragmented architectonics of bone tissue, which was observed up to 21 days. From the side of the synovial membrane, villous hyperplasia, lymphoid infiltration, and the appearance of additional layers of synoviocytes were observed as a result of a proliferative reaction. The most pronounced changes were observed in the integumentary layer of the synovium. After a single injection of a cryopreserved placenta, the signs of inflammation significantly decreased: the area of destruction of cartilage and bone was limited, and signs of mucoid swelling in the synovium decreased. Processes of functional blood filling of the microvasculature prevailed over ischemic ones. Stimulation of regenerative processes provided structural recovery on day 21 of observation. Conclusions. Prepartions of cryopreserved placenta influence the course of the inflammatory process in experimental osteoarthritis. The most reliable therapeutic effect is determined from the side of the synovium. [ABSTRACT FROM AUTHOR]

We present a new mathematical model of the aseptic inflammation dynamics. The adequacy of the model is confirmed by a qualitative and quantitative agreement with the laboratory data on the dynamics of the inflammatory process factors in the central zone of wound damage. We show that the model adequately describes not only the classical version of this process but also the available scenarios of acute and chronic inflammatory processes in aseptic cutaneous wound accompanied by the most common dysfunctions of blood cells or its cellular composition. [ABSTRACT FROM AUTHOR]

Abstract—Lymph heart of frog are hollow pulsating organs 1–2 mm in diameter that pump lymph into the venous system. They were used in this work as an experimental model to study the processes of initiation and development of aseptic inflammation in damaged tissues and necrosis-like death of mast cells (MCs). The ultrastructure of damaged and dying MCs was studied in striated muscle tissue of the posterior lymph heart of the adult frog in conditions of temporary ischemia (hypoxia) caused by autotransplantation of this organ into its own bed. It was found that damaged MCs die via oncotic necrosis after autotransplantation of the lymph heart within the period of time from 3 days to 6 weeks. Swelling of the cells and their membrane organelles (except for cytoplasmic secretory granules), dilatation of perinuclear space, budding of vesicles strewn with ribosomes from the outer nuclear membrane, and enrichment of nuclei of some MCs with heterochromatin occur at the early stages of oncosis. For late stages of oncotic necrosis, disintegration of the plasma membrane, release of intact and structurally little modified secretory granules into extracellular space, and karyolysis are typical. The presence of presumably nuclear material was found in extended perinuclear spaces of some damaged and dying MCs. The release of vesicles of rough endoplasmic reticulum (RER) into extracellular space was detected in places of local violation of the plasma membrane integrity of still undestroyed MCs. Immunocytochemical labeling of MCs using antibodies to histamine, substance P (SP), and atrial natriuretic peptide (ANP) (conducted at the ultrastructural level) detected the localization of aurum particles both over secretory granules located in the cytoplasm of damaged and dying cells and over the granules released into extracellular space after disintegration of MCs. Data obtained in the present study suggest that MCs dying via oncotic necrosis may be involved in the initiation and development of aseptic inflammatory process in autotransplanted lymph heart of frog and be a source of alarmins that contribute to the development of inflammation. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effect of low-level laser therapy (LLLT) on experimentally induced inflammation in retrodiscal tissues of the rabbit temporo mandibular joint (TMJ) using scintigraphic imaging. Methods: Eleven male New Zealand rabbits were included in this study. Six randomly selected rabbits were imaged to provide normal joint images (normal group) before the initiation of the experiment. A 5% formalin solution was locally injected into both right and left TMJs of all rabbits. Subsequently, Ga-Al-As laser (wavelength: 815 nm; energy density: 12 J/cm²; output power: 250 mW) was applied for 48 seconds. The treatment was performed six times for 2 weeks to the left TMJ of all rabbits. The right TMJs of the rabbits were used as the control (nontreated) TMJ group, while left TMJs were used as the treated TMJ group. Static images of TMJ were taken at 24 hours, 7 days, and 14 days after the beginning of the treatment. The images of all TMJs were taken in the posteroanterior direction with the rabbit under sedation and its mouth open. The Mann-Whitney U test was used to compare group differences, and intragroup differences were determined by the Friedman test and Wilcoxon sign test. Results: Significant differences were found between normal and both the control and treated TMJ groups. A reduction of inflammation in both treated and control TMJ groups was obtained, but there was no statistically significant difference between the groups. Conclusion: Under the conditions used in this study, quantitative scintigraphic measurements of TMJ inflammation of the treated TMJ group decreased but did not differ significantly from those of the control TMJ group. [ABSTRACT FROM AUTHOR]

BACKGROUND: Platelet-rich plasma therapy provides a new direction for the healing and repair of Achilles tendon injury. Its application has become a hot topic in recent years at home and abroad, showing a good application prospect.OBJECTIVE: To review the mechanism of action of platelet-rich plasma therapy at home and abroad and the current status and research progress of the treatment of Achilles tendinopathy.METHODS: A computer-based retrieval of CNKI, WanFang, and PubMed databases was performed for related articles published from January 2009 to September 2018. The keywords were "platelet-rich plasma(PRP), tendinopathy, Achilles tendinitis, Achilles tendon rupture,growth factor" in Chinese and English, respectively. The articles related to platelet-rich plasma therapy, healing and repair of Achilles tendinopathy, for summary and result analysis.RESULTS AND CONCLUSION: Forty-five eligible articles were included for analysis. The concentration of growth factors is the key to the treatment of Achilles tendon injury. Compared with conservative treatment and simple surgery, platelet-rich plasma therapy holds better imaging performance, functional scoring and quality of life. However, there is no uniform standard for preparation, concentration and injection method of platelet-rich plasma therapy in Achilles tendon injury. Platelet-rich plasma therapy still lacks clear and rigorous clinical guidelines. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect and mechanisms of naringenin in TiO2-induced chronic arthritis in mice, a model resembling prosthesis and implant inflammation.Treatment: Flavonoids are antioxidant and anti-inflammatory molecules with important anti-inflammatory effect. Mice were daily treated with the flavonoid naringenin (16.7-150 mg/kg, orally) for 30 days starting 24 h after intra-articular knee injection of 3 mg of TiO2.Methods: TiO2-induced arthritis resembles cases of aseptic inflammation induced by prosthesis and/or implants. Mice were stimulated with 3 mg of TiO2 and after 24 h mice started to be treated with naringenin. The disease phenotype, treatment toxicity, histopathological damage, oxidative stress, cytokine expression and NFκB were evaluated after 30 days of treatment.Results: Naringenin inhibited TiO2-induced mechanical hyperalgesia (96%), edema (77%) and leukocyte recruitment (74%) without inducing toxicity. Naringenin inhibited histopathological index (HE, 49%), cartilage damage (Toluidine blue tibial staining 49%, and proteoglycan 98%), and bone resorption (TRAP-stained 73%). These effects were accompanied by inhibition of oxidative stress (gp91phox 93%, NBT 83%, and TBARS 41%) cytokine mRNA expression (IL-33 82%, TNFα 76%, pro-IL-1β 100%, and IL-6 61%), and NFκB activation (100%).Conclusion: Naringenin ameliorates TiO2-induced chronic arthritis inducing analgesic and anti-inflammatory responses with improvement in the histopathological index, cartilage damage, and bone resorption. [ABSTRACT FROM AUTHOR]

Pigs are used with increased frequency to model different kinds of orthopedic surgical conditions. In order to show the full potential of porcine models in orthopedic research, it is therefore required to examine the expression of bone regulatory genes in pigs affected by orthopedic surgery and compare it to the expression in humans and mice as mice, are one of the most applied animal species in orthopedics today. In the present study, the local molecular response to drilling of a tibial implant cavity, and the subsequent insertion of a steel implant was examined in a porcine model. Pigs were euthanized five days after drilling of the bone. The molecular response of 73 different genes was analyzed using a high-throughput quantitative polymerase chain reaction platform and compared to histopathology. Histologically, it was found that bone remodeling was initiated on day 5 after surgery and was associated with upregulation of several genes involved in bone degradation and formation (CTSK, ACP5, IBSP, RANK, RANKL and COL1A1). Interleukin-6 and several acute-phase proteins (C3, SAA and ITIH4) were significantly upregulated, indicating their importance in the initial process of healing and osseointegration. All tested bone morphogenic proteins (BMP2, -4 and -7) including their inhibitor noggin were also significantly upregulated. Surprisingly, vascular endothelial growth factor A was not found to be regulated five days after surgery while several other vascular growth factors (ANGPT1, ANGPT2 and PTN) were upregulated. The pig was found to be a useful model for elucidation of bone regulatory genes in humans. [ABSTRACT FROM AUTHOR]

Aseptic peritonitis is a reaction of the local immune system aimed at rejection of a foreign body, which, having antigenic properties, does not (unlike a pathogen) counteract the immune system. The suture materials, namely catgut thread, used in intracavitary surgical operations possess xenogenic properties and can be used for antigenic stimulation of the immune system of the peritoneal cavity. Consequently, we decided to use a catgut suture for antigenic stimulation of the immune system of the peritoneal cavity and to study the morphological features of the results of experimental modeling of aseptic peritonitis in albino rats. The study involved 15 Wistar albino male rats, weighing 286,13 ± 6,26 g. To study the dynamics of destructive changes made by the catgut implant in the peritoneal cavity of the experimental animals, the animals were assigned into three groups in accordance with the time interval of their euthanasia at 3, 7, and 14 days of the experiment. After modeling an aseptic peritonitis, the investigation the abdominal cavity showed that in four out of five animals of the first group, that is, on day 3 of the experiment, the catgut implant had adhered to the greater omentum. The search for the fifth implant led to an unexpected discovery: we found it conjoined with the second derivative of the visceral peritoneum, similar in structure to the greater omentum, but related to the testes. On day 7, the implant embedded into the peritoneal cavity of the animals, had adhered to the serous formations of the testes in all five cases (100%, three of them – to the left epididymal omentum, and another two – to the right one). On day 14 (n = 5) it was found that in three cases it had adhered to the serous formations of the testes (60%, one of them to the left epididymal omentum, another two – to the right one) and in two cases it had adhered to the greater omentum (40%). During the experiment on implantation of a xenogenic substrate in the form of flat bundles made from the catgut thread into the peritoneal cavity of sexually mature male rats, it was found for the first time that their acceptors were not only the greater omentum, but also two derivatives of the peritoneum, homeomorphic to it and associated with the epididymides, which we reasonably called epididymal omenta and described in details. [ABSTRACT FROM AUTHOR]

• Purine metabolism and the relative concentration of adenosine were found to be downregulated during AL using widely targeted metabolomics. • CD73deficiencyexacerbated aseptic inflammation in vitro. • CD73 overexpression mitigated the titanium particle-mediated enhancement of LPS-induced M1 polarizationwhile promoting the titanium particle-mediated attenuation of IL-4-induced M2 polarization. • Intraarticular injection of recombinant mouse CD73 protein slightly delays the process of AL. Aseptic inflammation is a major cause of late failure in total joint arthroplasty, and the primary factor contributing to the development and perpetuation of aseptic inflammation is classical macrophage activation (M1 phenotype polarization) induced by wear particles. CD73 (ecto-5′-nucleotidase) is an immunosuppressive factor that establishes an adenosine-induced anti-inflammatory environment. Although CD73 has been shown to suppress inflammation by promoting alternate macrophage activation (M2 phenotype polarization), its role in wear particle-induced aseptic inflammation is currently unknown. Our experiments were based on metabolomic assay results in a mouse model of aseptic loosening, and studied the function of CD73 in vivo and in vitro using a mouse aseptic loosening model and a mouse bone marrow derived macrophage (BMDM) inflammation model. Results show that aseptic loosening (AL) reduces the purine metabolic pathway and decreases the native expression of the metabolite adenosine. In vivo, CD73 expression was low in the bone tissue surrounding the titanium nail and synovial-like interface tissue, while in vitro experiments demonstrated that CD73 knockdown promoted titanium particles-induced aseptic inflammation. CD73 overexpression mitigated the titanium particle-mediated enhancement of LPS-induced M1 polarization while promoting the titanium particle-mediated attenuation of IL-4-induced M2 polarization. In BMDM exposed to titanium particles, CD73 promotes M2 polarization via the p38 pathway. Meanwhile, local injection of recombinant mouse CD73 protein slightly alleviated the progression of AL. Collectively, our data suggest that CD73 alleviates the process of AL, and this function is achieved by promoting alternate activation of macrophages. [ABSTRACT FROM AUTHOR]

Ioannis G Fatouros, Athanasios Z Jamurtas School of Physical Education and Sport Sciences, University of Thessaly, Karies, Trikala, Greece Abstract: The study of exercise-induced muscle damage (EIMD) is of paramount importance not only because it affects athletic performance but also because it is an excellent model to study the mechanisms governing muscle cachexia under various clinical conditions. Although, a large number of studies have investigated EIMD and its associated inflammatory response, several aspects of skeletal muscles responses remain unclear. In the first section of this article, the mechanisms of EIMD are reviewed in an attempt to follow the events that result in functional and structural alterations of skeletal muscle. In the second section, the inflammatory response associated with EIMD is presented with emphasis in leukocyte accumulation through mechanisms that are largely coordinated by pro- and anti-inflammatory cytokines released either by injured muscle itself or other cells. The practical applications of EIMD and the subsequent inflammatory response are discussed with respect to athletic performance. Specifically, the mechanisms leading to performance deterioration and development of muscle soreness are discussed. Emphasis is given to the factors affecting individual responses to EIMD and the resulting interindividual variability to this phenomenon. Keywords: muscle damage, exercise, aseptic inflammation, recovery, immune system, redox status

The ubiquitin-proteasome system (UPS) is the main cellular proteolytic system responsible for the degradation of normal and abnormal (e.g. oxidised) proteins. Under catabolic conditions characterised by chronic inflammation, the UPS is activated resulting in proteolysis, muscle wasting and impaired muscle function. Milk proteins provide sulphur-containing amino acid and have been proposed to affect muscle inflammation. However, the response of the UPS to aseptic inflammation and protein supplementation is largely unknown. The aim of this study was to investigate how milk protein supplementation affects UPS activity and skeletal muscle function under conditions of aseptic injury induced by intense, eccentric exercise. In a double-blind, cross-over, repeated measures design, eleven men received either placebo (PLA) or milk protein concentrate (PRO, 4 × 20 g on exercise day and 20 g/d for the following 8 days), following an acute bout of eccentric exercise (twenty sets of fifteen eccentric contractions at 30°/s) on an isokinetic dynamometer. In each trial, muscle biopsies were obtained from the vastus lateralis muscle at baseline, as well as at 2 and 8 d post exercise, whereas blood samples were collected before exercise and at 6 h, 1 d, 2 d and 8 d post exercise. Muscle strength and soreness were assessed before exercise, 6 h post exercise and then daily for 8 consecutive days. PRO preserved chymotrypsin-like activity and attenuated the decrease of strength, facilitating its recovery. PRO also prevented the increase of NF-κB phosphorylation and HSP70 expression throughout recovery. We conclude that milk PRO supplementation following exercise-induced muscle trauma preserves proteasome activity and attenuates strength decline during the pro-inflammatory phase. [ABSTRACT FROM AUTHOR]

In this work the study of the influence of subcutaneous transplantation of cryoconservated placenta on the experimental acute aseptic inflammation of rat testes was carried. The research was carried on 65 Vistar male rats. The experimental aseptic inflammation was caused by intraperitoneal injection of 5 mg -caraginen (“Sigma Co”) in 1 ml 0,9% solution of sodium chloride. The transplantation of cryoconservated placenta by a single subcutaneous injection was made. Testes were taken in 6, 12, 24 hours and on 2nd, 3rd, 5th, 7th, 10th day after beginning of aseptic inflammation and after placenta injection. Thin sections were stained by metilen blue. It was determined that on 7th day after the beginning of experiment the phenomenon of edema of connective tissue diminished. The blood supply at the microcirculatory level was renewed on 7-10th day of experiment. The destruction, desqumation, discomplexation of spermatogonia, spermatocytes I and II, spermatids have dimin-ished also by this term. On a 10th day the gradual renewal of cellular layers and wholeness of basal parts of epithelium of seminiferous tubules was determined. Thus, after injection of placenta there is renewal of cellular composition of spermato-genic epithelium in testes with aseptic inflammation.

The characteristics of cell's phases experimental aseptic inflammation with indicate levels of interleukin-1β, interleukin-10, corticosterone are presented. The area of aseptic inflammation, have logical relay of cell's populations, IL-1β, IL-10, corticosterone are regulate cell's processes. And by 20 days inflammatory process complete formation dense connective capsule.

Objectives: Mechanical loading is a potential activator of inflammation and able to stimulate factors for periodontal and alveolar bone destruction. Aim of this study was to investigate the inflammatory response and synthesis of proteinases by human periodontal ligament fibroblast (HPdLF) dependent on different strengths of static tensile strain (STS). Materials and methods: HPdLFs were loaded with different STS strengths (1, 5, and 10 %) in vitro. Gene expressions of cyclooxygenase (COX)-2 and interleukin (IL)-6 were analyzed by quantitative real-time polymerase chain reaction. Production of IL-6, prostaglandin E (PGE), matrix metalloproteinase (MMP)-8, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were measured by enzyme-linked immunosorbent assay. Receptor activator of nuclear factor-kappa ligand (RANKL) synthesis was detected by immunocytochemical staining. Results: Ten percent STS led to an increased gene expression of IL-6 and COX-2 (34.4-fold) in HPdLF, and 1 and 5 % STS slightly reduced the gene expression of IL-6. Synthesis of IL-6 was significantly reduced by 1 % STS and stimulated by 10 % STS. Ten percent STS significantly induced PGE production. RANKL was not detectable at any strength of STS. MMP-8 synthesis showed significantly higher values only at 10 % STS, but TIMP-1 was stimulated by 5 and 10 % STS, resulting into highest TIMP-1/MMP-8 ratio at 5 % STS. Conclusions: High-strength STS is a potent inducer of periodontal inflammation and MMP-8, whereas low-strength STS shows an anti-inflammatory effect. Moderate-strength STS causes the highest TIMP-1/MMP-8 ratio, leading to appropriate conditions for reformation of the extracellular matrix. Clinical relevance: Furthermore, this study points out that the strength of force plays a pivotal role to achieve orthodontic tooth movement without inducing periodontal inflammation and to activate extracellular matrix regeneration. [ABSTRACT FROM AUTHOR]

Mice carrying a deletion of the adhesive extracellular domain of the desmosomal cadherin desmoglein 2 develop an arrhythmogenic right ventricular cardiomyopathy-like phenotype with ventricular dilation, fibrosis and arrhythmia. To unravel the sequence of myocardial alterations and to identify potential pathomechanisms, histological analyses were performed on mutant hearts from the juvenile to the adult state, i.e., between 2 and 13 weeks. At an age of 2 weeks 30% of mutants presented lesions, which were visible as white plaques on the heart surface or in the septum. From 4 weeks onwards, all mutants displayed a cardiac phenotype. Dying cardiomyocytes with calcification were found in lesions of all ages. But lesions of young mutant animals contained high amounts of CD45+ immune cells and little collagen fibers, whereas lesions of the older animals were collagen-rich and harbored only a small but still significantly increased number of CD45+ cells. Electron microscopy further showed that distinct desmosomes cannot be distinguished in intercalated discs of mutant hearts. Widening of the intercellular cleft and even complete dissociation of intercalated discs were often observed close to lesions. Disturbed sarcomer structure, altered Z-discs, multiple autophagic vacuoles and swollen mitochondria were other prominent pathological features. Taken together, the following scenario is suggested: mutant desmoglein 2 cannot fully support the increased mechanical requirements placed on intercalated disc adhesion during postnatal heart development, resulting in compromised adhesion and cell stress. This induces cardiomyocyte death, aseptic inflammation and fibrotic replacement. The acute stage of scar formation is followed by permanent impairment of the cardiac function. [ABSTRACT FROM AUTHOR]

Autogenous bone grafts are widely used in the repair of bone defects. Growth factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration and enhance bone growth. The combination of an autogenous bone graft and BMP-2 may provide a better osteogenic effect than either treatment alone, but BMP-2 is easily inactivated in body fluid. The objective of this study was to develop a technique that can better preserve the in vivo activity of BMP-2 incorporated in bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid) (PLGA) delayed-release microspheres, and then combined collagen, the delayed-release microspheres, and rat autologous bone particulates to form four groups of composite grafts with different combinations: collagen in group A; collagen combined with bone particulates in group B; collagen combined with BMP-2/PLGA delayed-release microspheres in group C; and collagen combined with both bone particulates and BMP-2/PLGA delayed-release microspheres in group D. The four groups of composite grafts were implanted into the gluteus maximus pockets in rats. The ectopic osteogenesis and ALP level in group D (experimental group) were compared with those in groups A, B, and C (control groups) to study whether it had higher osteogenic capability. Results showed that the composite graft design increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume of autologous bone. The selection of bone particulate diameter had an impact on the osteogenetic potential of bone grafts. Collagen prevented the occurrence of aseptic inflammation and improved the osteoinductivity of BMP-2. These results showed that this composite graft design is effective and feasible for use in bone repair. [ABSTRACT FROM AUTHOR]

Introduction Variability in response to acetaminophen (APAP)-induced aseptic inflammation and tolerance to the impending hepatic damage has been described. To understand the mechanism of adaptive tolerance, we investigated the proteomic profiles of crude nuclear lysates in a mouse model. We hypothesized that pretreatment with low doses of APAP prior to a toxic dose results in differential protein expression. Materials and Methods Mice (BALB/C) were separated into three groups: the pretreated (PT) group received incremental doses of APAP while the last dose only (LD) and naive groups were given saline vehicle. A toxic dose of APAP was administered on the seventh day to the PT and LD animals only and all groups were euthanized 3 h postdose. Total protein from crude hepatic nuclear lysates were applied to protein arrays and analyzed by immunoaffinity mass spectrometry. Results and Discussion Comparative data analyses of protein peaks revealed a protein that was significantly increased at m/z of 60,030 (p60) in the LD animals vs the other two groups. The closest match for the preliminary identification of the p60 protein based on a Swiss-Prot/ Tagldent database search using the approximate isoelectric point and molecular weight information was Ccr4-Not complex subunit-2. This protein is a subunit of a multiprotein complex and serves as a transcriptional suppressor involved in controlling mRNA synthesis and degradation. Preliminary identification was also supported by Western blot analysis using anti-CNOT2 antibody. Conclusion Considering the APAP tolerance model, we conclude that toxicogenomic approaches such as nuclear profiling are useful tools in assessing differential expression of transcriptional factors involved in inflammatory response and adaptive tolerance to toxins. [ABSTRACT FROM AUTHOR]