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A series of new tetrasubstituted α-aminophosphonate derivatives with a methylphosphoserine fragment were described. These compounds were synthesized by a three-component (3-CR) "Kabachnik-Fields reaction." The novel α-aminophosphonates were screened for in vivo anti-inflammatory activity through topical and oral administration routes. All compounds decreased TPA-induced ear edema in a dose-dependent fashion. In this test, compounds 2, 5, and 7 showed the same efficacy (≈ 90%) and higher potency than indomethacin and decreased the inflammatory marker neutrophil-to-lymphocyte ratio (NLR). Moreover, oral pretreatment and post-treatment with compounds 2-7 reduced CFA-induced paw edema, as did indomethacin or (S)-naproxen. Based on the promising in vivo anti-inflammatory results, we investigated their physicochemical and pharmacokinetics profiles in silico. The analysis also revealed that the novel tetrasubstituted α-aminophosphonates did not break Lipinski's rule of five and had drug-likeness and favorable ADME properties for oral and transdermal administration.

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Dithranol is one of the most effective topical medications for treating plaque psoriasis. However, its clinical use is limited by irritative adverse reactions to the skin, such as oedema, erythema, and pruritus, caused by poorly understood mechanisms. Because TRPV1 activation mediates skin irritation caused by several drugs, we conducted blind and randomised experiments in male and female C57BL/6 mice to elucidate the role of TRPV1 in dithranol-induced irritation. Dithranol (0.01%-0.5%) or vehicle was applied topically to the right ear of the animals. Oedema, erythema, and pruritus were monitored from 2 h to 6 days after application. Treatment with 0.5% dithranol caused oedema and erythema, but not pruritus, starting at 6 h, reaching its highest point at 1 day, and persisting up to 6 days after treatment, mainly in male mice. The 0.1% dose induced erythema but not oedema. Interestingly, topical application of 1% capsaicin was shown to defunctionalise TRPV1-positive fibres and did not influence early irritation caused by dithranol (2 h-2 days). However, it increased the late phase of irritation (5-6 days). Similarly, salicylate did not reduce the early irritation caused by dithranol but also increased the late phase. Antagonism by SB366791 and 4-tert-butylcyclohexanol did not alter skin irritation. Our results suggest that, contrary to our initial hypothesis, TRPV1 appears to act protectively against skin irritation caused by dithranol, particularly in the late stage.

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BACKGROUND: Bothrops venom consists primarily of metalloproteinase and phospholipase A2 toxins, which are responsible for the acute inflammatory, coagulant and hemorrhagic action following snakebite. The local effects of snakebite envenomation by Bothrops species are particularly prevalent yet poorly studied, but include pain, edema, erythema, blistering, bleeding, and ecchymosis. METHODS AND FINDINGS: In this study, we describe the dermatopathological findings observed in a series of 22 patients diagnosed with Bothrops envenomation treated in a tertiary hospital of Manaus, in the Brazilian Amazon. Clinically, pain and edema were observed in all patients, followed by fang marks (63.6%), secondary infection (36.3%), ecchymosis (31.8%), erythema (22.7%), blister (13.6%), and necrosis (4.5%). Regarding histopathological findings, epidermal alterations such as spongiosis, acanthosis and hyperkeratosis were the most observed characteristics in our cases series, with isolated cases of hyperplasia, hemorrhagic intraepidermal blister and severe necrosis. Changes in dermis and hypodermis consisted mainly of hemorrhage, inflammatory infiltrate, edema, congestion, and vascular damage, whereas cases of collagen damage, necrosis, abscess, and signs of tissue repair, indicated by the presence of granulation tissue, were also observed, with a persistence of inflammatory and hemostatic alterations even days after antivenom administration. Therefore, the tissue damage resulting from Bothrops envenomation could be related to both direct venom activity as well as inflammatory response or presence of infectious process. The histopathological analysis of human skin injury can enlighten the pathological and endogenous effects of local envenomation and could underpin new strategies, including novel treatments, adjuvants or changes in clinical management, that lead to better outcomes in snakebite patients.

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BACKGROUND Compartment syndrome of the forearm has been associated with a variety of etiologies, including fractures, snake bites, complications of certain infections, and, very rarely, spider bites. Loxoscelism is the venom-related clinical manifestation of the bite of spiders of the genus Loxosceles, also called brown or fiddler (violinist) spiders. It manifests locally/regionally with pain, erythema, and edema, with subsequent necrotic plaque formation at the site of the bite. This condition can threaten the function and integrity of the limbs and, in severe cases, can be life-threatening. The basis of treatment is surgical decompression of the affected compartments to restore limb perfusion and avoid irreversible sequelae. CASE REPORT A 62-year-old male patient, without comorbidities, had edematous cutaneous loxoscelism and secondary development of acute compartment syndrome of the right forearm. He promptly visited the Emergency Department and underwent surgical treatment, in addition to the application of pharmacological treatment, under a multidisciplinary team. The evolution was favorable. The biochemical levels of rhabdomyolysis decreased, the compartment syndrome resolved, the fasciotomies were closed, and the patient was discharged without further complications. CONCLUSIONS Although arachnid bites are relatively uncommon in urban hospitals, it is crucial that general, vascular, and plastic surgeons maintain a high index of clinical suspicion for acute compartment syndrome. It is important to make an accurate differential diagnosis, and equally important is the interdisciplinary approach to treating this condition, ensuring prompt medical treatment and, if necessary, early surgical intervention.

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INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common oncological disease in the pediatric population; however, skin infiltration occurs only in 1-3% of the patients and almost always manifests after the diagnosis is made. CLINICAL CASE: A male teenage patient who presented with facial edema and infiltration, associated with systemic symptoms such as asthenia and adynamia. On physical examination, the patient presented facial edema and indurated plaques, as well as cervical, inguinal, and axillary adenopathy. Complete blood count showed pancytopenia and a chest X-ray revealed a mediastinal mass. Due to a high suspicion of malignancy a bone marrow and skin biopsy was taken, both with pre-B ALL. Chemotherapy was started and the patient is now in maintenance phase. CONCLUSIONS: Leukemia cutis manifestations are heterogenous, from a small papule to a big nodule. It is more common in patients with acute myeloid leukemia and it is rare in patients with pre-B ALL, specially in the pediatric population. The diagnosis should be done with a biopsy and the treatment is with systemic chemotherapy. The diagnosis should always be considered in patients with unexplained edematous or indurated lesions, especially in the context of systemic symptoms.

INTRODUCCIÓN: La leucemia linfoblástica aguda es la enfermedad oncológica más común en la edad pediátrica; sin embargo, la infiltración a la piel solo ocurre en el 1-3% de los pacientes y se manifiesta habitualmente posterior al diagnóstico de leucemia. CASO CLÍNICO: Adolescente varón que acude a urgencias de nuestra unidad por presentar edema facial persistente, junto con astenia y adinamia. En la exploración física presenta edema facial con placas difusas induradas y adenopatía cervical, inguinal y axilar. Se decide realizar una biometría hemática, que muestra pancitopenia, y una radiografía de tórax, que revela una masa mediastinal. Por sospecha de malignidad se decide realizar una biopsia de médula ósea y de piel, dando como resultado leucemia linfoblástica pre-B en ambas. Se inició quimioterapia y actualmente se encuentra en fase de mantenimiento. CONCLUSIONES: Las manifestaciones clínicas de leucemia cutis son heterogéneas, desde una pápula pequeña hasta lesiones nodulares de diferentes tamaños. Lo más común es verlas en pacientes con leucemia mieloide aguda, y es muy raro en pacientes con leucemia linfoblástica aguda pre-B, especialmente en la edad pediátrica. El diagnóstico se realiza con una biopsia de piel y el tratamiento es con quimioterapia sistémica. Es importante tener en mente este diagnóstico en pacientes con síntomas sistémicos de leucemia.

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Edema of the psoas major muscle can indicate various pathologies, such as infection, malignancy, and trauma, but it can also result from benign causes like delayed-onset muscle soreness (DOMS). This article presents the case of a 44-year-old female patient who developed DOMS in the psoas major after participating in an intense abdominal workout. The patient reported hip pain that began a day after the workout, which was confirmed by magnetic resonance imaging (MRI) revealing significant edema in the psoas major muscles, particularly on the right side. Conservative treatment with rest and analgesics led to full recovery within two weeks. DOMS, typically associated with eccentric exercises, can be mistaken for more serious conditions, but its recognition is crucial to avoid unnecessary investigations and interventions. This case highlights the importance of clinical history and imaging findings in distinguishing DOMS from other causes of muscle edema, emphasizing the need for accurate diagnosis to ensure appropriate management.

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This study aims to evaluated the impact of poly(ε-caprolactone) (PCL) microspheres on the pharmacokinetics and pharmacodynamics (PopPK/PD) of 6-methylcoumarin (6MC). For this, PCL microspheres loaded with 6MC were prepared using the emulsification-evaporation method. Particle size, zeta potential, drug loading, and entrapment efficiency were characterised by dynamic light scattering and UV spectrophotometry. In vitro release and pharmacokinetics in Wistar rats were assessed for free and encapsulated 6MC. Anti-inflammatory activity was evaluated using the carrageenan-induced paw edoema model, with PopPK and PopPK/PD models developed. Microspheres showed diameters between 2.9 and 7.1 µm, zeta potentials of -10 to -15 mV, and drug loading of 0.24 mg/mg. Encapsulation efficiency was 45.5% to 75.9%. PopPK models showed enhanced absorption and distribution, with increased anti-inflammatory potency of encapsulated 6MC. PCL microspheres significantly improved the pharmacokinetic and pharmacodynamic profiles of 6MC, enhancing its therapeutic potential for lipophilic drugs.

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Chronic disease inflammation requires safe complementary treatments. The pericarp of Passiflora tripartita var. mollissima (PTM) contains potential anti-inflammatory metabolites. This study aimed to evaluate the bioactive components, antioxidant capacity, and anti-inflammatory effects of PTM extracts at two ripening stages. The bioactive compounds in the hydrophilic and lipophilic extracts of mature and green pericarps were identified by GC-MS and UV-VIS, while the antioxidant capacity was measured by free radical reduction. Anti-inflammatory effects were tested using a rat paw edema model with carrageenan-induced edema, indomethacin, or PTM extracts (100, 250, and 500 mg/kg). The effect of mature hydrophilic extract was further evaluated in an air pouch model, where rats received the placebo, carrageenan, indomethacin, or the extract (500 and 1000 mg/kg). Leukocytes, cytokines, and markers of oxidative stress were evaluated. The results showed the presence of organic compounds, total phenols, and flavonoids. The mature hydrophilic extract exhibited the highest antioxidant activity. At 500 mg/kg, it reduced edema, leukocyte migration, and levels of IL-1ß, IL-6, and TNF-α while managing oxidative stress and preventing histological damage. In conclusion, PTM contains bioactive compounds with potential pharmacological properties. The hydrophilic extract of the mature pericarp, at a dose of 500 mg/kg, exhibits an enhanced antioxidant and anti-inflammatory effect.

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Cardiotonic steroids are known to bind to Na+/K+-ATPase and regulate several biological processes, including the immune response. The synthetic cardiotonic steroid γ-Benzylidene Digoxin 8 (BD-8) is emerging as a promising immunomodulatory molecule, although it has remained largely unexplored. Therefore, we tested the immunomodulatory potential of BD-8 both in vitro and in vivo. Hence, primary mouse macrophages were incubated with combinations of BD-8 and the pro-inflammatory fungal protein zymosan (ZYM). Nitric oxide (NO) production was determined by Griess reagent and cytokines production was assessed by enzyme-linked immunosorbent assay. Inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), p-nuclear factor kappa B p65 (NF-κB p65), p-extracellular signal-regulated kinase (p-ERK), and p-p38 were evaluated by flow cytometry. Macrophages exposed to BD-8 displayed reduced phagocytic activity, NO levels, and production of the proinflammatory cytokine IL-1ß induced by ZYM. Furthermore, BD-8 diminished the expression of iNOS and phosphorylation of NF-κB p65, ERK, and p38. Additionally, BD-8 exhibited anti-inflammatory capacity in vivo in a carrageenan-induced mouse paw edema model. Taken together, these findings demonstrate the anti-inflammatory activity of BD-8 and further reinforce the potential of cardiotonic steroids and their derivatives as immunomodulatory molecules.

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Objetivos: Describir las características epidemiológicas y evolución de la enfermedad de nueve pacientes con diagnóstico de Angioedema Hereditario (AEH), asistidos en la Unidad de Alergia e Inmunología del Hospital Municipal de Agudos de Bahía Blanca. Métodos: Diseño del Estudio: De Corte Trans- versal, descriptivo y exploratorio, cuantitativo. Se utilizaron como instrumentos las historias clínicas de nueve pacientes y una encuesta enviada a cada uno de ellos por google drive para confirmación y comparación de los datos obtenidos. En todos los casos se obtuvo el consentimiento informado autorizando la utilización y potencial publicación de los datos obtenidos. Resultados: las encuestas fueron analizadas y expresadas con recursos de la Estadística descriptiva, donde la medida de frecuencia utilizada fue la de porcentaje, sin realizar métodos de estadística inferencial. Conclusiones: El AEH es una enfermedad compleja, hereditaria, de difícil diagnóstico y con gran afectación de la calidad de vida de quienes la padecen.

Aim of this study is to describe the epidemiological charac- teristics and clinical evolution of 9 patients with a diagnosis of Hereditary Angioedema (HAE), treated in the Allergy and Immunology Unit of the Hospital Municipal de Agudos de Bahía Blanca. Materials and Methods: Study Design: Cross-sectional, descriptive and exploratory, quantitative. The clinical history of the 9 patients and a survey sent to each of them via Google Drive were used as data source for confirmation and comparison. In all cases, informed consent was obtained authorizing the use and potential publication of the data obtained. Results: the surveys were analyzed and expressed, and with resources of descriptive statistics, where the frequency measure used was percentage, without using inferential statistical methods. Conclusions: Angioedema is a complex hereditary disease, very difficult

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Introducción. Los pacientes con edema malar crónico, montículos malares y festones representan un desafío para el cirujano plástico, ya que la patología persiste aún después de la blefaroplastia inferior tradicional. Objetivo. El objetivo del trabajo es evaluar la efi cacia del lifting de tercio medio facial para el tratamiento de festones adquiridos, analizar el desarrollo de la técnica y evaluar complicaciones. Materiales y métodos. Desde mayo de 2022 a mayo de 2023, 17 pacientes fueron operados de blefaroplastia inferior transcutánea con lifting supraperióstico de tercio medio facial para tratamiento de festones malares adquiridos. Resultados. La edad media de la población del estudio fue de 61 años. La duración del procedimiento fue en promedio de 2 hs. El tiempo medio de seguimiento posoperatorio fue de 8 meses, sin evidencia de recurrencia de festones. Conclusiones. El lifting supraperióstico de tercio medio facial es una opción segura, reproducible y efi caz para el tratamiento de festones. Sin embargo, deben respetarse todos los pasos de la técnica para evitar así complicaciones y recidivas

Background. Festoons and malar mounds present a particular challenge to the plastic surgeon and commonly persist after the traditional lower blepharoplasty. Material and methods. From May 2022 to May 2023, 17 patients underwent preperiosteal midcheek lift by transcutaneous lower eyelid incision for acquired festoons treatment. Results. The average patient age was 61 years. The procedure took on average 2 hours, with a median follow-up of 8 months without evidence of recurrent festoons. Conclusion. Preperiosteal midcheek lift is a reproducible, reliable and eff ective procedure for festoons treatment. However, all surgical technique steps must be considered to avoid complications and recurrence of the disease.

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OBJECTIVES: Resveratrol has been studied as a potential agent for treating rheumatic conditions; however, this compound suppresses glucose synthesis and glycogen catabolism when infused in perfused livers of both arthritic and healthy rats. This study investigated the effects of oral administration of resveratrol on inflammation and liver metabolism in rats with arthritis induced by Freund's adjuvant, which serves as rheumatoid arthritis model. METHODS: Holtzman rats, both healthy and exhibiting arthritic symptoms, were orally treated with resveratrol at doses varying from 25 to 500 mg/kg for a 5-day period preceding arthritis induction, followed by an additional 20-day period thereafter. Paw edema, arthritic score and hepatic myeloperoxidase activity were assessed to evaluate inflammation. Glycogen catabolism and gluconeogenesis from lactate were respectively evaluated in perfused livers from fed and fasted rats. RESULTS: Resveratrol decreased the liver myeloperoxidase activity at doses above 100 mg/kg, and decreased the paw edema and delayed the arthritic score at doses above 250 mg/kg. The hepatic gluconeogenesis was decreased in arthritic rats and resveratrol did not improve it. However, resveratrol did not negatively modify the gluconeogenesis in livers of healthy and arthritic rats. Glycogen catabolism was in part and slightly modified by resveratrol in the liver of arthritic and healthy rats. CONCLUSIONS: It is improbable that resveratrol negatively affects the liver metabolism, especially considering that gluconeogenesis is highly fragile to changes in cellular architecture. The findings suggest that resveratrol could serve as alternative for treating rheumatoid arthritis. Nevertheless, prudence is advised regarding its transient effects on liver metabolism.

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BACKGROUND: Treatment for edema involves multiple approaches, with Kinesiotaping having recently emerged as an option for edema reduction. OBJECTIVE: To systematically summarize current evidence on the effects of Kinesiotaping on edema reduction on any type of edema. METHODS: A systematic review was performed including randomized clinical trials that compared the effects of Kinesiotaping to any other intervention or no intervention on edema. Screening, assessment of methodological quality (PEDro scale) of studies, and confidence of evidence (GRADE) were analyzed by two independent reviewers. A quantitative summary is presented through meta-analyses. RESULTS: A total of 3750 studies were identified, of which 70 were included in this review, and were organized by body region (face, upper limbs and lower limbs) and by treatment time (short and long term). It was observed that Kinesiotaping was superior to comparison groups in the short-term for face edema (Standardized mean difference [SMD] -1.07; 95%CI -1.48 to -0.65) and lower limbs (SMD -0.55; 95%CI -1.06 to -0.05). Also, Kinesiotaping was superior to comparison group in the long-term for lower limbs (SMD -0.72; 95%CI -1.25 to -0.18). Kinesiotaping was not superior to the comparison groups for upper limbs in both the short (SMD -0.05; 95%CI -0.89 to 0.80) and long-term (SMD -0.04; 95%CI -0.31 to 0.24) protocols. CONCLUSION: Kinesiotaping seems to be an effective intervention to reduce acute edema around the face and potentially in the lower limbs in both short and long-term protocols, although the quality of evidence is very low. However, these positive results were not observed for the upper limbs.

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INTRODUCTION: Vaginal delivery has several benefits for the parturient; however, during labor, some injuries, such as lacerations and/or episiotomy, can occur. Perineal pain may occur in the puerperium and can be aggravated in cases of perineal injury during childbirth, potentially impacting the physical and emotional aspects of the parturient. For this reason, it is necessary to use techniques that can relieve pain and edema in the immediate postpartum period, directly influencing recovery. OBJECTIVE: To compare the reduction of pain and improvement in healing using two techniques, namely photobiomodulation and cryotherapy, performed in the immediate postpartum period of up to 12 h, in parturients who suffered grade I and II lacerations and/or episiotomy. METHODS: Data collection was carried out through an evaluation questionnaire. Photobiomodulation was applied using the red and infrared laser from the DMC brand. The EVA and McGill scales were used for pain assessment, and the REEDA scale was used for the evaluation of edema and healing. RESULTS: The techniques were evaluated and applied to 56 patients, with 28 in each group (cryotherapy and LBI). Patients who received photobiomodulation showed superior improvement compared to cryotherapy. In the immediate postpartum period, there was a greater reduction in pain in favor of photobiomodulation (p = 0.008); and after 24 h, the difference was even more significant (p < 0.001).

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In recent years there has been an extraordinary increase in the use of different filler materials as facial cosmetic treatments. The popularity of injectable tissue fillers among individuals who wish to restore volume and gain a more youthful appearance is because it is a minimally invasive esthetic procedure for soft tissue augmentation. However, although they are considered efficient and safe, they can trigger complications such as swelling, bruising, erythema, pain, infection, nodule formation, vascular occlusion, and pigmentary changes. The objective of this article was to present a case of a 46-year-old patient who presented with significant facial edema 3 months after lip and infraorbital filling with hyaluronic acid, resistant to medication, which appeared and worsened after starting to use Ozempic for weight loss. Therefore, we chose to perform an intralesional application of hyaluronidase 2.000utr, immediately observing the decrease in edema. After a week, the patient was completely recovered, with no signs of edema, no allergic reactions and feeling very well. The etiology of late inflammatory reactions is unclear and we believe that some medications may be capable of initiating these immune responses. Hyaluronidase is an effective treatment to reverse adverse reactions from hyaluronic acid injection, dissolving the peptide bond proteins within the hyaluronic acid, increasing the viscosity of the material and allowing it to be dispersed throughout the soft tissue.

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Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.

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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)

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Chysobalanus icaco L. (C. icaco) is a plant that is native to tropical America and Africa. It is also found in the southeast region of Mexico, where it is used as food and to treat certain diseases. This study aimed to carry out a phytochemical analysis of an aqueous extract of C. icaco seed (AECS), including its total phenol content (TPC), total flavonoid content (TFC), and condensed tannins (CT). It also aimed to examine the antioxidant and metal-ion-reducing potential of the AECS in vitro, as well as its toxicity and anti-inflammatory effect in mice. Antioxidant and metal-ion-reducing potential was examined by inhibiting DPPH, ABTS, and FRAP. The acute toxicity test involved a single administration of different doses of the AECS (0.5, 1, and 2 g/kg body weight). Finally, a single administration at doses of 150, 300, and 600 mg/kg of the AECS was used in the carrageenan-induced model of subplantar acute edema. The results showed that the AECS contained 124.14 ± 0.32 mg GAE, 1.65 ± 0.02 mg EQ, and 0.910 ± 0.01 mg of catechin equivalents/g dried extract (mg EC/g de extract) for TPC, TFC and CT, respectively. In the antioxidant potential assays, the values of the median inhibition concentration (IC50) of the AECS were determined with DPPH (0.050 mg/mL), ABTS (0.074 mg/mL), and FRAP (0.49 mg/mL). Acute toxicity testing of the AECS revealed no lethality, with a median lethal dose (LD50) value of >2 g/kg by the intragastric route. Finally, for inhibition of acute edema, the AECS decreased inflammation by 55%, similar to indomethacin (59%, p > 0.05). These results demonstrated that C. icaco seed could be considered a source of bioactive molecules for therapeutic purposes due to its antioxidant potential and anti-inflammatory activity derived from TPC, with no lethal effect from a single intragastric administration in mice.

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ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea eriogyne Benth (Fabaceae) is popularly known as "Jatobá". Despite its use in folk medicine to treat inflammatory disorders, there are no descriptions that show its anti-inflammatory potential. AIM OF THE STUDY: In this sense, this study aimed to evaluate the anti-inflammatory and antivenom action of bark and leaves extract of H. eriogyne. MATERIALS AND METHODS: The in vivo anti-inflammatory activity was conducted by carrageenan-induced paw edema and zymosan-induced air pouch models, evaluating the edematogenic effect, leukocyte migration, protein concentration, levels of pro-inflammatory cytokines, malondialdehyde (MDA) and myeloperoxidase (MPO) activity. The antivenom potential was investigated in vitro on the enzymatic action (proteolytic, phospholipase and hyaluronidase) of Bothrops brazili and B. leucurus venom, as well as in vivo on the paw edema model induced by B. leucurus. Furthermore, the influence of its markers (astilbin and rutin) on MPO activity was investigated in silico. For molecular docking, AutodockVina, Biovia Discovery Studio, and Chimera 1.16 software were used. RESULTS: The extracts and bark and leaves of H. eriogyne revealed a high anti-inflammatory effect, with a reduction in all inflammatory parameters evaluated. The bark extract showed superior results when compared to the leaf extract, suggesting the influence of the astilbin concentration, higher in the bark, on the anti-inflammatory action. In addition, only the H. eriogyne bark extract was able to reduce MDA, indicating an associated antioxidant effect. Regarding the in vitro antivenom action, the extracts (bark and leaves) revealed the ability to inhibit the proteolytic, phospholipase and hyaluronidase action of both bothropic venom, with a greater effect against B. leucurus venom. In vivo, extracts from the bark and leaves of H. eriogyne (50-200 mg/kg) showed antiedematogenic activity, reducing the release of MPO and pro-inflammatory cytokines, indicating the presence of bioactive components useful in controlling the inflammatory process induced by the venom. In the in silico assays, astilbin and rutin showed reversible interactions of 9 possible positions and orientations towards MPO, with affinities of -9.5 and -10.4 kcal/mol and interactions with Phe407, Gln91, His95 and Arg239, important active pockets of MPO. Rutin demonstrated more effective types of interactions with MPO. CONCLUSION: This approach reveals for the first time the anti-inflammatory action of H. eriogyne bark and leaf extracts in vivo, as well as its antiophidic potential. Moreover, the distinct effect of pharmacogens as antioxidant agents and distinct effect of astilbin and rutin under MPO sheds light on the different anti-inflammatory mechanisms of bioactive compounds present in H. eriogyne extracts, with high potential for the prospection of new pharmacological agents.