NLRP3 Inflammasome Expression in Gingival Crevicular Fluid of Patients with Periodontitis and Chronic Hepatitis C

The study is aimed at assessing the impact that periodontal disease and chronic hepatitis C could have on gingival crevicular fluid levels of the NLRP3 inflammasome, caspase-1 (CASP-1), and interleukin-18 (IL-18) and at evaluating whether the increased local inflammatory reaction with clinical periodontal consequences is correlated to their upregulation. Patients were divided into four groups, according to their periodontal status and previously diagnosed hepatitis C, as follows: (i) CHC group, chronic hepatitis C patients; (ii) P group, periodontal disease patients, systemically healthy; (iii) CHC + P group, patients suffering from both conditions; and (iv) H group, systemically and periodontally healthy controls. Gingival crevicular samples were collected for quantitative analysis of the NLRP3 inflammasome, CASP-1, and IL-18. CHC + P patients expressed the worse periodontal status and the highest NLRP3, CASP-1, and IL-18 levels, the difference being statistically significant ( p < 0.05 ). The P group patients also expressed significantly more elevated NLRP3, CASP-1, and IL-18 levels, as compared to nonperiodontal patients (CHC and H groups). Chronic hepatitis C and periodontal disease could have a significant influence on the upregulation of NLRP3 inflammasome and its components, possibly contributing to an increased local inflammatory reaction and clinical periodontal consequences.

Leptin and leptin receptor evaluation in atherosclerotic plaques in patients with type 2 diabetes mellitus

Background. Diabetes mellitus (DM) is a significant predictor of atherosclerosis, cardiovascular disease, and cardiovascular mortality. It is known that atherosclerosis occurs earlier in patients with diabetes, reducing the duration of their life. Leptin as well as other inflammatory markers can contribute to the progression of atherosclerosis in patients with DM, participate in the development of a local inflammatory reaction. Aim. Determine the cells immunophenotype of atherosclerotic plaques in patients with diabetes. Materials and methods. We analyzed 24 patients (20 men and 4 women), who underwent aortofemoral bypass, femoral-tibial bypass or carotid endarterectomy. During the operation, a fragment of the arterial wall with an atherosclerotic plaque was obtained for further immunohistochemical studies. Five histologic plaque characteristics (CD68+, -SMA, CD34, leptin and leptin receptor) were compared. Results. No difference in the expression of CD68 (p=0.922), -SMA (p=0.192), CD34 (p=0.858), leptin receptor (p=0.741) and leptin (p=0.610) in atherosclerotic plaques were observed between patients with and without DM. The lack of significant differences between the two groups was possibly due to the small number of observations with DM. In particular, when assessing the expression of selected markers in atherosclerotic plaques, patients with DM showed significantly more leptin receptors than patients without DM (2160.716 and 1205.88 respectively); and also significantly less CD68+ (0.39 and 0.98 respectively) and -SMA+ (6.5 and 13.5 respectively). Conclusion. Based on the expression of CD68, -SMA, CD34, leptin receptor and leptin, no significant differences were observed in atherosclerotic plaque between patients with and without DM. At the same time, despite the limitations of the study (a small number of patients, moderate severity of DM, elderly patients in the DM group), we found a tendency in the increased number of leptin receptors and a decreased number of -SMA+, CD68+ in DM atherosclerotic plaques. Further study needed, taking into account the limitations of this work.

High-Dose Immunoglobulin G Suppresses Local Inflammatory Reaction and Facilitates Functional Recovery Following Olfactory System Injury

BackgroundHead trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti-inflammatory treatment using steroids or anti-cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high-dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury. MethodsOlfactory nerve transection (NTx) was performed in OMP-tau-lacZ mice to establish injury models. High-dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42 and 100 days after the drug injection. X-gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test.ResultsHigh-dose IgG-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG-injected mice. ConclusionsThese findings suggest that high-dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

IRAK-4 in macrophages contributes to inflammatory osteolysis of wear particles around loosened hip implants

TLRs recognizing PAMPS play a role in local immunity and participate in implant-associated loosening. TLR-mediated signaling is primarily regulated by IL-1 receptor associated kinase-M (IRAK-M) negatively and IRAK-4 positively. Our previous studies have proved that wear particles promote endotoxin tolerance in macrophages by inducing IRAK-M. However, whether IRAK-4 is involved in inflammatory osteolysis of wear particles basically, and the specific mechanism of IRAK-4 around loosened hip implants, is still unclear. IRAK-4 was studied in the interface membranes from patients in vivo and in particle-stimulated macrophages to clarify its role. Also, IL-1β and TNF-α levels were measured after particle and LPS stimulation in macrophages with or without IRAK-4 silenced by siRNA. Our results showed that the interface membranes around aseptic and septic loosened prosthesis expressed more IRAK-4 compared with membranes from osteoarthritic patients. IRAK-4 in macrophages increased upon particle and LPS stimulation. In the former, IL-1β and TNF-α levels were lower compared with those of LPS stimulation, and IRAK-4 siRNA could suppress production of pro-inflammatory cytokines. These findings suggest that besides IRAK-M, IRAK-4 also plays an important role in the local inflammatory reaction and contributes to prosthesis loosening.

Trastuzumab-emtansine induced pleural and pericardial effusions

Introduction Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate which combine trastuzumab (T), a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), and a cytotoxic molecule derived from maytansine (DM1). Case report We report the first case of T-DM1-associated pleural and pericardial effusions three weeks after the second course of T-DM1 in a patient with breast cancer. Drug-induced pleural and pericardial effusions was implicated in the absence of other etiologies. The Naranjo Scale indicated a probable drug-induced adverse reaction. Management & outcome: The patient fully recovered after thoracentesis and discontinuation of T-DM1. The patient has reported no side effect after the sixth course of trastuzumab. Discussion To our knowledge, this is the first case in the literature of bilateral pleural and pericardial effusions in a patient treated with T-DM1. The successful initiation of treatment with trastuzumab following withdrawal of T-DM1 suggests that emtansine played a role in the development of bilateral pleural and pericardial effusions. We hypothesize that the patient’s condition was a result of a local inflammatory reaction to emtansine by direct toxicity.

APPLICATION OF COMBINED TWO-LEVEL SPINAL-EPIDURAL ANESTHESIA WITH FIXATION OF EPIDURAL CATHETER IN SUBCUTANEOUS CANAL USING MODIFIED CEREBROSPINAL NEEDLE

The aim of the study is to assess the advantages of a new technique for conducting a combined two-level spinal-epidural anesthesia with fixation of an epidural catheter in the subcutaneous canal using a modified spinal needle among elderly and senile patients during operations for fracture of the lower extremity bones. Material . We analyzed 44 cases of combined two-level spinal-epidural anesthesia with epidural catheter fixation in the subcutaneous canal using a modified cerebrospinal needle in lower limb bone fracture surgeries among elderly and senile patients over 2019. The developed technique of combined two-level spinal-epidural anesthesia with fixation of the epidural catheter in the subcutaneous canal using a modified cerebrospinal needle made it possible to exclude cases of catheter migration by more than 1 cm and avoid development of local inflammatory reaction. Conclusion . Combined two-level spinal-epidural anesthesia with the fixation of an epidural catheter in the subcutaneous canal using a modified cerebrospinal needle is a reliable, effective and safe anesthesia technique for operations for hip fracture among elderly and senile patients and makes it possible to perform long-term postoperative analgesia without the risk of infectious complications and complications associated with dislocation of the epidural catheter.

A possible relationship between Thromboxane B2 and Leukotriene B4 and the encapsulation of Dirofilaria repens worms in human subcutaneous dirofilariasis

Human subcutaneous dirofilariosis has several clinical presentations. Many cases present as subcutaneous nodules, as a consequence of a local inflammatory reaction that encapsulates and destroys the worms. In addition, there are cases in which migrating worms located in the ocular area remain unencapsulated. In the present work, the levels of two pro-inflammatory eicosanoids, thromboxane B2 (TxB2) and leukotriene B4 (LTB4) are analysed by commercial Enzime-Linked immunosorbent assay (ELISA) in serum samples from 43 individuals, 28 diagnosed as having subcutaneous dirofilariasis presenting a subcutaneous nodule, five diagnosed as having dirofilariasis, in which the worms remained unencapsulated in the periphery of the eye, and ten healthy individuals living in a non-endemic area, used as controls. The worms were surgically removed, identifying Dirofilaria repens as the causative agent in all cases, by Polymerase Chain Reaction (PCR). Individuals with nodules showed significantly higher levels of TxB2 and LTB4 than healthy controls, whereas significant differences in LTB4 levels were observed between individuals with unencapsulated worms and healthy controls. It is speculated that the absence of LTB4 may contribute to the fact that worms remain unencapsulated as a part of immune evasion mechanisms.

The use of polypropylene mesh in thoracoplasty: an experimental and clinical study

Relevance. Thoracoplasty is an effective way to close the cavity of destruction of the lung tissue and achieve clinical recovery in case of fibro-cavernous pulmonary tuberculosis. A promising direction of creating selective collapse in thoracoplasty is the use of synthetic mesh implants. The purpose of the study was to assess the effect of synthetic implants from the “Surgipro" polypropylene mesh on the inflammatory and reparative reaction in thoracoplasty. Materials and methods. The work was performed on male Wistar rats weighing 250±50 grams (n=12). The “Surgipro” polypropylene mesh was implanted on the right posterolateral surface of the chest (n=9). As control, the material was taken from intact rats (n=3), which were kept in the same conditions as experimental animals. The study material was biopsy specimens of the muscular aponeurotic scar of the posterolateral surface of the chest of rats. The cellular composition and total number of mast cells were determined. A clinical study was conducted on 26 cases of thoracoplastic with the use of polypropylene mesh in the pulmonary-surgical department of the Seaside regional antituberculous dispensary in Vladivostok. Results. During the experimental study, it was recorded that the implant used in the reconstruction of the chest has a pronounced reactogenicity from the first day, which manifests itself as a local inflammatory reaction with the concentration of mast cells. The population of mast cells progressively declined by the 30th day, while an increase in the number of macrophages and fibroblasts was observed with the advent of giant multinuclear cells of foreign bodies. On the 30th day after the operation, a widespread post-inflammatory reactive fibrosis and angiomatosis with chronic productive inflammation was observed in the experiment. In clinical observation, the resulting inflammatory reaction around the endoprosthesis spreads to the surrounding tissues and lung, which contributes to the formation of pronounced pulmonary fibrosis and restriction of a specific process.