Manejo cirúrgico de ferimento auto-infligido por arma de fogo em região maxilofacial / Surgical management of self-inflicted injury by gun in the maxillofacial region

INTRODUÇÃO: O manejo dos pacientes vítimas de PAF possui vertentes divergentes a respeito do tratamento cirúrgico, que pode ser realizado de forma imedata ou tardia. Em lesões auto-infligidas, a distância entre a arma e a região acometida é menor, causando consequências estéticas e funcionais mais devastadoras. Aliado ao fato desse tipo de trauma criar uma ferida suja devido à comunicação com a cavidade oral e seios paranasais, o manejo das lesões representam um desafio mesmo à cirurgiões experientes. OBJETIVO: Estre trabalho relata o manejo cirúrgico de uma ferida auto-infligida por arma de fogo que resultou em avulsão dos tecidos moles na região maxilofacial. DESCRIÇÃO DO CASO: Paciente do sexo masculino, 35 anos, vítima de projétil de arma de fogo auto-infligido em região maxilofacial, cursando com extenso ferimento em região de língua e mento. Clinicamente, o paciente não apresentava sinais de fratura em ossos da face. Ambos os ferimentos apresentavam secreção purulenta e o paciente manifestava disfonia devido a grande destruição tecidual. CONSIDERAÇÕES FINAIS: O tratamento de ferimentos por arma de fogo não só é um grande desafio para o cirurgião, como para toda a equipe multidisciplinar requerida para tais casos, visto que não há protocolos bem definidos para o tratamento dessas lesões(AU)

INTRODUCTION: The management of patients who are victims of FAP has divergent aspects regarding surgical treatment, which can be performed immediately or late. In self-inflicted injuries, the distance between the weapon and the affected region is smaller, causing more devastating aesthetic and functional consequences. Allied to the fact that this type of trauma creates a dirty wound due to the communication with the oral cavity and paranasal sinuses, the management of injuries represents a challenge even for experienced surgeons. OBJECTIVE: This paper reports the surgical management of a self-inflicted gunshot wound that resulted in soft tissue avulsion in the maxillofacial region. CASE DESCRIPTION: Male patient, 35 years old, victim of a self-inflicted firearm projectile in the maxillofacial region, coursing with extensive injury in the region of the tongue and chin. Clinically, the patient did not show signs of facial bone fractures. Both wounds had purulent secretion and the patient had dysphonia due to extensive tissue destruction. FINAL CONSIDERATIONS: The treatment of gunshot wounds is not only a great challenge for the surgeon, but also for the entire multidisciplinary team required for such cases, since there are no well-defined protocols for the treatment of these injuries(AU)

In Silico Analysis: Anti-Inflammatory and α-Glucosidase Inhibitory Activity of New α-Methylene-γ-Lactams.

The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1-7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.

Anasarca as the first presentation of anti-synthetase syndrome.

A woman in her 70s presented with anasarca and exertional dyspnoea. Investigation showed severe hypoalbuminaemia with no urinary or gastrointestinal protein losses. CT thorax reported lung consolidations, and transbronchial lung biopsy demonstrated organising pneumonia. Autoimmune myositis serology was positive for anti-Jo-1, anti-Ro-52, and anti-PM/Scl-100 antibodies. She was diagnosed with anti-synthetase syndrome with organising pneumonia. She was treated with oral prednisolone and oral mycophenolate mofetil with a good clinical response.

Fenamates and ibuprofen as foundational components in the synthesis of innovative, targeted COX-2 anti-inflammatory drugs, undergoing thorough biopharmacological assessments and in-silico computational studies.

Cyclooxygenase-2 plays a vital role in inflammation by catalyzing arachidonic acid conversion toward prostaglandins, making it a prime therapeutic objective. Selective COX-2 inhibitors represent significant progress in anti-inflammatory therapy, offering improved efficacy and fewer side effects. This study describes the synthesis of novel anti-inflammatory compounds from established pharmaceutically marketed agents like fenamates III-V and ibuprofen VI. Through rigorous in vitro testing, compounds 7b-c, and 12a-b demonstrated substantial in vitro selective inhibition, with IC50 values of 0.07 to 0.09 µM, indicating potent pharmacological activity. In vivo assessment, particularly focusing on compound 7c, revealed significant anti-inflammatory effects. Markedly, it demonstrated the highest inhibition of paw thickness (58.62 %) at the 5-hr mark compared to the carrageenan group, indicating its potency in mitigating inflammation. Furthermore, it exhibited a rapid onset of action, with a 54.88 % inhibition observed at the 1-hr mark. Subsequent comprehensive evaluations encompassing analgesic efficacy, histological characteristics, and toxicological properties indicated that compound 7c did not induce gastric ulcers, in contrast to the ulcerogenic tendency associated with mefenamic acid. Moreover, compound 7c underwent additional investigations through in silico methodologies such as molecular modelling, field alignment, and density functional theory. These analyses underscored the therapeutic potential and safety profile of this novel compound, warranting further exploration and development in the realm of pharmaceutical research.

Association of Preoperative Subchondral Bone Marrow Oedema with Outcomes after Lateral Unicompartmental Knee Arthroplasty.

OBJECTIVE: To determine whether the presence of preoperative subchondral bone marrow oedema (SBME) is associated with inferior outcomes after lateral unicompartmental knee arthroplasty (LUKA). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Orthopaedic Surgery, Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, Chongqing, China, from January 2019 to June 2022. METHODOLOGY: Data on patients treated with LUKA were obtained from the Medical Registry Database. Two groups were made based on the presence and absence of SBME on preoperative magnetic resonance imaging (MRI). The visual analogue scale (VAS), American Knee Society Scores (AKSS), and rate of patient satisfaction were compared between the two groups. RESULTS: A total of 20 patients treated with LUKA were reviewed. The SBME was present in 9 cases and absent in 11 cases. Patients with SBME had inferior scores at preoperative evaluation and at 1, 3, and 6 months postoperatively. However, there was no significant difference between the groups at the 12-month follow-up. Eight (88.9%) patients with SBME were satisfied with the LUKA surgery versus 9 (81.8%) patients without SBME, showing no significant differences between groups. CONCLUSION: Presence of preoperative SBME is associated with inferior functional outcomes after LUKA within six months of follow-up. KEY WORDS: Bone marrow, Oedema, Knee, Arthroplasty, Outcome, Patient satisfaction.

Edema of the upper extremity on the unaffected side in unilateral breast cancer patients.

Breast cancer-related lymphedema (BCRL) occurs usually on the affected side, and its cause and pathophysiology are well known. However, the cause of edema of the upper extremity on the unaffected side is barely known. It is often considered to be chemotherapy-induced general edema, and clinical evaluation is rarely performed in these patients. This study aimed to present the clinical characteristics of unilateral breast cancer patients with edema of upper extremity on the unaffected side, and to emphasize the importance of early diagnosis and medical interventions. This study retrospectively analyzed the medical records of unilateral breast cancer patients complaining edema of upper extremity on the unaffected side, from January 2020 to May 2021. Lymphoscintigraphy was used to assist in confirming the diagnosis of lymphedema, and Doppler ultrasonography or 3D computed tomography angiography were performed to differentiate vascular problems. Fourteen patients were enrolled in the study. Seven, 3, and 4 patients had edema of both upper extremities, edema of the upper extremity on the unaffected side only, and edema of all extremities, respectively. None of the 4 patients with edema of all extremities showed abnormal findings on examination. In patients with edema in the upper extremity on the unaffected side alone, lymphatic flow dysfunction was seen in 2 patients, and deep vein thrombosis (DVT) was diagnosed in 1. In patients with edema of both upper extremities, lymphatic flow dysfunction was seen in 2 patients, and DVT was diagnosed in 3. One patient had DVT and accompanying lymphatic flow dysfunction. Lymphedema and DVT were diagnosed in a number of patients with edema of the upper extremity on the unaffected side, and lymphedema can occur without direct injury to the lymphatic flow system. Therefore, clinicians should not overlook the fact that diseases that require early diagnosis and treatment can occur in patients with edema of the unaffected upper extremity.

Large birth mark and unilateral swelling of the lower extremity in a young teenager.

We describe an early adolescent male who was diagnosed with vascular malformation associated with unilateral limb overgrowth based on the clinical findings of a persistent port-wine stain since birth and gradually progressing right lower limb oedema since early childhood. Clinicians should keep in mind to clinically evaluate such malformations in detail, as well as contemplate genetic testing in patients presenting with a large port-wine stain at birth, particularly if well demarcated and lateral in a lower extremity.

Anti-inflammatory properties and characterization of water extracts obtained from Callicarpa kwangtungensis Chun using in vitro and in vivo rat models.

Callicarpa kwangtungensis Chun (CK) is a common remedy exhibits anti-inflammatory properties and has been used in Chinese herbal formulations, such as KangGongYan tablets. It is the main component of KangGongYan tablets, which has been used to treat chronic cervicitis caused by damp heat, red and white bands, cervical erosion, and bleeding. However, the anti-inflammatory effects of CK water extract remains unknown. This study assessed the anti-inflammatory effects of CK in vivo and in vitro, characterized its main components in the serum of rats and verified the anti-inflammatory effects of serum containing CK. Nitric oxide (NO), tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) release by RAW264.7 cells was examined by ELISA and Griess reagents. Inflammation-related protein expression in LPS-stimulated RAW264.7 cells was measured by western blotting. Furthermore, rat model of foot swelling induced by λ-carrageenan and a collagen-induced arthritis (CIA) rat model were used to explore the anti-inflammatory effects of CK. The components of CK were characterized by LC-MS, and the effects of CK-containing serum on proinflammatory factors levels and the expression of inflammation-related proteins were examined by ELISA, Griess reagents and Western blotting. CK suppressed IL-6, TNF-α, and NO production, and iNOS protein expression in LPS-stimulated RAW264.7 cells. Mechanistic studies showed that CK inhibited the phosphorylation of ERK, P38 and JNK in the MAPK signaling pathway, promoted the expression of IκBα in the NF-κB signaling pathway, and subsequently inhibited the expression of iNOS, thereby exerting anti-inflammatory effects. Moreover, CK reduced the swelling rates with λ-carrageenan induced foot swelling, and reduced the arthritis score and incidence in the collagen-induced arthritis (CIA) rat model. A total of 68 compounds in CK water extract and 31 components in rat serum after intragastric administration of CK were characterized. Serum pharmacological analysis showed that CK-containing serum suppressed iNOS protein expression and NO, TNF-α, and IL-6 release. CK may be an anti-inflammatory agent with therapeutic potential for acute and chronic inflammatory diseases, especially inflammatory diseases associated with MAPK activation.

Surgical Treatment of Medically Refractory Encapsulating Peritoneal Sclerosis in a Patient After Kidney Transplant.

Encapsulating peritoneal sclerosis is a rare but highly morbid disease process in patients with end-stage kidney disease on peritoneal dialysis. Surgical management has been described in patients with encapsulation of bowel causing obstruction. Here, we describe a case of surgical management in a patient following kidney transplant with medically refractory ascites and lower extremity edema.

Probability of Occult Ankle Fracture Based on Radiograph-Measured Swelling.

INTRODUCTION: Pediatric ankle injuries are a common presentation in the emergency department (ED). A quarter of pediatric ankle fractures show no radiographic evidence of a fracture. Physicians often correlate non-weight bearing and tenderness with an occult fracture. We present this study to predict the probability of an occult fracture using radiographic soft-tissue swelling on initial ED radiographs. METHODS: This is a retrospective study at a Level 1 pediatric trauma center from 2021 to 22. Soft-tissue swelling between the lateral malleolus and skin was measured on radiographs, and weight-bearing status was documented. Statistical analysis was conducted using Stata software. DISCUSSION: The study period involved 32 patients with an occult fracture, with 8 (25%) diagnosed with a fracture on follow-up radiographs. The probability of an occult fracture was calculated as a function of the ankle swelling in millimeters (mm) using a computer-generated predictive model. False-negative and false-positive rates were plotted as a function of the degree of ankle swelling. CONCLUSION: Magnitude of ankle soft-tissue swelling as measured on initial ED radiographs is predictive of an occult fracture. Although weight-bearing status was not a sign of occult fracture, it improves the predictive accuracy of soft-tissue swelling.

Common Comorbidities in Patients with Remitting Seronegative and Symmetrical Synovitis with Pitting Edema (RS3PE).

OBJECTIVES: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is considered a rare inflammatory rheumatologic disorder that is seen primarily in older adult men. Patients present with arthralgias of large joints accompanied by painful pitting edema of the hands and feet. Few studies have reported the prevalence of metabolic syndromes, including diabetes mellitus and hyperlipidemia in these patients. METHODS: This case series reviewed 25 patients who were diagnosed as having RS3PE in a private outpatient clinic. RESULTS: Nearly half of the patients (48%) had diabetes mellitus, predominantly type 2, and more than half of the patients (60%) had hyperlipidemia. CONCLUSIONS: We believe that future case studies on RS3PE should include an assessment of various comorbidities that can be seen in patients with this autoinflammatory disorder. The increased availability of musculoskeletal ultrasound provides a potential area of study to differentiate this disorder from other inflammatory arthritis and improve reaching the correct diagnosis.

Diagnostic performance of unenhanced electrocardiogram-gated cardiac CT for detecting myocardial edema.

To assess the diagnostic performance of unenhanced electrocardiogram (ECG)-gated cardiac computed tomography (CT) for detecting myocardial edema, using MRI T2 mapping as the reference standard. This retrospective study protocol was approved by our institutional review board, which waived the requirement for written informed consent. Between December 2017 to February 2019, consecutive patients who had undergone T2 mapping for myocardial tissue characterization were identified. We excluded patients who did not undergo unenhanced ECG-gated cardiac CT within 3 months from MRI T2 mapping or who had poor CT image quality. All patients underwent unenhanced ECG-gated cardiac CT with an axial scan using a third-generation, 320 × 0.5 mm detector-row CT unit. Two radiologists together drew regions of interest (ROIs) in the interventricular septum on the unenhanced ECG-gated cardiac CT images. Using T2 mapping as the reference standard, the diagnostic performance of unenhanced cardiac CT for detecting myocardial edema was evaluated by using the area under the receiver operating characteristic curve with sensitivity and specificity. Youden index was used to find an optimal sensitivity-specificity cutoff point. A cardiovascular radiologist independently performed the measurements, and interobserver reliability was assessed using intraclass correlation coefficients for CT value measurements. A P value of <.05 was considered statistically significant. We included 257 patients who had undergone MRI T2 mapping. Of the 257 patients, 35 patients underwent unenhanced ECG-gated cardiac CT. One patient was excluded from the study because of poor CT image quality. Finally, 34 patients (23 men; age 64.7 ±â€…14.6 years) comprised our study group. Using T2 mapping, we identified myocardial edema in 19 patients. Mean CT and T2 values for 34 patients were 46.3 ±â€…2.7 Hounsfield unit and 49.0 ±â€…4.9 ms, respectively. Mean CT values moderately correlated with mean T2 values (Rho = -0.41; P < .05). Mean CT values provided a sensitivity of 63.2% and a specificity of 93.3% for detecting myocardial edema, with a cutoff value of ≤45.0 Hounsfield unit (area under the receiver operating characteristic curve = 0.77; P < .01). Inter-observer reproducibility in measuring mean CT values was excellent (intraclass correlation coefficient = 0.93; [95% confidence interval: 0.86, 0.96]). Myocardial edema could be detected by CT value of myocardium in unenhanced ECG-gated cardiac CT.

Temporal Swelling Following Cochlear Implantation: Frequency, Treatment, and Outcomes.

OBJECTIVE: To investigate the frequency, treatment, and outcomes of postoperative delayed-onset swelling around cochlear implants. STUDY DESIGN: Retrospective, observational, nonrandomized group study. SETTING: Academic medical center. PATIENTS/INTERVENTIONS: Among 354 patients (516 ears) who underwent cochlear implantation (CI) at our hospital between May 2009 and October 2022, 329 (472 ears: 138 children [246 ears] and 191 adults [226 ears]) with a follow-up period of >3 months were included. MAIN OUTCOME MEASURES: Physical examination and computed tomography of the head were performed. RESULTS: In total, 5.5% (26/472 ears) had a history of delayed-onset swelling around the implant. This complication occurred in 9.8% (24/246 ears) of children and 0.9% (2/226 ears) of adults. The mean time to onset of swelling was 50 (range, 5.5-147) months following CI. In 60% (21/35) of the cases, the cause was unknown, whereas in 25.7% (9/35) and 11.5% (4/35) of cases, it was head trauma and acute inflammation, respectively. Conservative treatment (observation, antibiotics, and/or strong magnetic compression) was adapted in 91.4% (32/35) of cases. After conservative treatment, revision CI surgery was performed in one ear. Additionally, recurrent swelling was observed in 23.1% (6/26 ears) of swelling cases. CONCLUSIONS: The results suggest that delayed-onset swelling around implants occurs more frequently in children than in adults because of the higher incidence rates of head trauma and acute otitis media in children. In most cases, conservative treatment was adequate; however, careful follow-up is necessary. Our findings can serve as a reference for optimizing care and intervention options after CI.

Exploring the anti-inflammatory, sedative, antidiabetic, and antioxidant potential in in-vitro and in-vivo models and phenolic profiling of Atractylis aristata Batt.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylis aristata batt., as an endemic plant from the Asteraceae family, holds a significant position in the Ahaggar region of southern Algeria's traditional medicine. The aerial parts of Atractylis aristata was used to cure inflammation, fever, and stomach disorders. AIM OF THE STUDY: The objective of the present investigation was to ascertain the overall bioactive components and phytochemical components and examine the antioxidant, antidiabetic, anti-inflammatory, acute toxicity, and sedative properties of the crude extract obtained from the aerial portions of Atractylis aristata (AaME). MATERIALS AND METHODS: The AaME's antioxidant activity was assessed by the use of pyrogallol autoxidation, (1,1 diphenyl-2-picrylhydrazyl) (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power (RP) techniques. 1 mg/mL of AaME was used to evaluate the antidiabetic activity by applying the enzyme α-amylase inhibitory power test. At the same time, the bovine serum albumin (BSA) denaturation method was employed to quantify the in vitro anti-inflammatory activity at different concentrations (1.5625, 0.78125, 0.390625, 0.1953125 and 0.09765625 mg/mL). In contrast, following the Organization for Economic Co-operation and Development (OECD) guideline No. 423, which covers acute oral toxicity testing protocols, the limit dosage test was employed to assess in vivo acute toxicity. At the dose of 0.08 mg/mL, the carrageenan-induced paw edema approach was used to assess the anti-inflammatory efficacy in vivo, and the sedative activity was carried out at the dose of 0.08 mg/mL using the measurement of the locomotor method. Different bioactive compounds were identified within AaME using LC-MS/MS and HPLC-UV analysis. RESULTS: The acute toxicity study showed no fatalities or noticeable neurobehavioral consequences at the limit test; this led to their classification in Globally Harmonized System (GHS) category Five, as the OECD guideline No 423 recommended. At a concentration of 0.08 mg/mL (2000 mg/kg), AaME showed apparent inhibition of paw edema and a significant (p = 0.01227) reduction in locomotor activity compared to the control animals. Our findings showed that AaME exhibited considerable antioxidant (IC50 = 0.040 ± 0.003 mg/mL (DPPH), IC50 = 0.005 ± 5.77 × 10-5 mg/mL (ABTS), AEAC = 91.15 ± 3.921 mg (RP) and IR% = 23.81 ± 4.276 (Inhibition rate of pyrogallol) and rebuts antidiabetic activities (I% = 57.6241% ± 2.81772). Our findings revealed that the maximum percentage of BSA inhibition (70.84 ± 0.10%) was obtained at 1.562.5 mg/mL. Thus, the AaME phytochemical profile performed using phytochemical screening, HPLC-UV, and LC-MS/MS analysis demonstrated that A. aristata can be a valuable source of chemicals with biological activity for pharmaceutical manufacturers. CONCLUSION: The phytochemical profiling, determined through HPLC-UV and LC-MS/MS applications, reveals this plant's therapeutic value. The aerial parts of Atractylis aristata contain bioactive molecules such as gallic acid, ascorbic acid, and quercetin, contributing to its significant antioxidant capabilities. Furthermore, identifying alizarin, the active compound responsible for its anti-inflammatory properties, could provide evidence supporting the anti-inflammatory capabilities of this subspecies.

Bone marrow edema of the knee: a narrative review.

Bone marrow edema (BME) is a frequent MRI finding in patients with knee pain. According to the etiology, BME of the knee can be classified into three main categories: ischemic, mechanic, and reactive. The diagnosis may be difficult, because of the specificity of symptoms and the poor radiographic findings. MRI is the gold standard, showing an area of altered signal of the bone with an high signal intensity on fat-suppressed, T2 weighted images, usually in combination with an intermediate or low signal intensity on T1 weighted images. Bone marrow edema tends to be self-limiting and, in most cases, resolves without any consequences in a varying amount of time. However, since it may evolve to complete joint destruction, early diagnosis and correct treatment are crucial to prevent the articular degeneration. Conservative therapy is the first step, with no weight-bearing for 3 to 6 weeks on the affected side, in combination with the administration of anti-inflammatory drugs or painkillers to manage symptoms. In non-responding forms and more advanced stages, minimally invasive preservative surgery can provide significant results, with subchondroplasty and core decompression being the two main procedures available. Knee arthroplasty, both total (TKA) or unicompartmental (UKA), is the only effective option when the degradation of cartilage is diffuse and in patients with subchondral bone collapse.

Tolvaptan therapy for edema in patients with chronic kidney disease.

OBJECTIVE: Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. MATERIALS AND METHODS: The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. RESULTS: During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p < 0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. CONCLUSION: As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.

A novel diselenide attenuates the carrageenan-induced inflammation by reducing neutrophil infiltration and the resulting tissue damage in mice.

Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl (k = 9.2 x 107 M-1s-1), like glutathione (k = 1.2 x 108 M-1s-1), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC50=4.6 µM) and purified myeloperoxidase (MPO) (IC50=3.8 µM). However, tyrosine, MPO-I and MPO-II substrates, did not restore HOCl formation in presence of DD. DD inhibited the oxidative burst in dHL-60 cells with no toxicity up to 25 µM for 48h. Next, an intraperitoneal administration of 25, 50, and 75 mg/kg DD decreased total leukocyte, neutrophil chemotaxis, and inflammation markers (MPO activity, lipid peroxidation, albumin exudation, nitrite, TNF-α, IL-1ß, CXCL1/KC, and CXCL2/MIP-2) on a murine model of carrageenan-induced peritonitis. Likewise, 50 mg/kg DD (i.p.) decreased carrageenan-induced paw edema over 5h. Histological and immunohistochemistry analyses of the paw tissue showed decreased neutrophil count, edema area, and MPO, carbonylated, and nitrated protein staining. Furthermore, DD treatment decreased the fMLP-induced chemotaxis of human neutrophils (IC50=3.7 µM) in vitro with no toxicity. Lastly, DD presented no toxicity in a single-dose model using mice (50 mg/kg, i.p.) over 15 days and in Artemia salina bioassay (50 to 2000 µM), corroborating findings from in silico toxicological study. Altogether, these results demonstrate that DD attenuates carrageenan-induced inflammation mainly by reducing neutrophil migration and the resulting damage from MPO-mediated oxidative burst.