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Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T. cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti-inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding.

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The molecular structures of nonsteroidal anti-inflammatory drugs (NSAIDs) vary, but most contain a carboxylic acid functional group (RCOOH). This functional group is known to be related to the mechanism of cyclooxygenase inhibition and also causes side effects, such as gastrointestinal bleeding. This study proposes a new role for RCOOH in NSAIDs: facilitating the interaction at the binding site II of serum albumins. We used bovine serum albumin (BSA) as a model to investigate the interactions with ligands at site II. Using dansyl-proline (DP) as a fluorescent site II marker, we demonstrated that only negatively charged NSAIDs such as ibuprofen (IBP), naproxen (NPX), diflunisal (DFS), and ketoprofen (KTP) can efficiently displace DP from the albumin binding site. We confirmed the importance of RCOO by neutralizing IBP and NPX through esterification, which reduced the displacement of DP. The competition was also monitored by stopped-flow experiments. While IBP and NPX displaced DP in less than 1 s, the ester derivatives were ineffective. We also observed a higher affinity of negatively charged NSAIDs using DFS as a probe and ultrafiltration experiments. Molecular docking simulations showed an essential salt bridge between the positively charged residues Arg409 and Lys413 with RCOO-, consistent with the experimental findings. We performed a ligand dissociation pathway and corresponding energy analysis by applying molecular dynamics. The dissociation of NPX showed a higher free energy barrier than its ester. Apart from BSA, we conducted some experimental studies with human serum albumin, and similar results were obtained, suggesting a general effect for other mammalian serum albumins. Our findings support that the RCOOH moiety affects not only the mechanism of action and side effects but also the pharmacokinetics of NSAIDs.

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OBJECTIVE: To verify, based on a systematic literature review, the effects of the main analgesics on male fertility. DATA SOURCES: The studies were analyzed from the PubMed, SciELO and LILACS databases. STUDY SELECTION: The articles selected for the present review included: cohort studies; cross-sectional studies, clinical trials; complete studies; studies with animal models that addressed the proposed theme and that were published within the stipulated period from March 1, 2013, to March 31, 2023, in English, Portuguese and Spanish. These would later have to go through inclusion stages such as framing the type of study and exclusion criteria. DATA COLLECTION: Author's name, year of publication, study population, number of patients, analgesic, administration time, dose, and effect. CONCLUSIONS: There are in vitro and in vivo studies that link paracetamol and ibuprofen to endocrine and seminal changes that are harmful to male fertility. However, more clinical research is needed to determine the doses and timing of administration that affect fertility. The effects of aspirin on male fertility are still unclear due to the lack of studies and consistent methodologies. There is not enough research on dipyrone and its relationship with male fertility, requiring more studies in this area.

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RATIONALE: Indomethacin (INDO) is a widely utilized non-steroidal anti-inflammatory drug (NSAID) with recognized effect on the central nervous system. Although previous reports demonstrate that prolonged treatment with indomethacin can lead to behavioral alterations such as anxiety disorder, the biochemical effect exerted by this drug on the brain are not fully understood. OBJECTIVES: The aim of present study was to evaluate if anxiety-like behavior elicited by indomethacin is mediated by brains oxidative stress as well as if alpha-tocopherol, a potent antioxidant, is able to prevent the behavioral and biochemical alterations induced by indomethacin treatment. METHODS: Zebrafish were utilized as experimental model and subdivided into control, INDO 1 mg/Kg, INDO 2 mg/Kg, INDO 3 g/Kg, α-TP 2 mg/Kg, α-TP 2 mg/Kg + INDO 1 mg/Kg and α-TP + INDO 2 mg/Kg groups. Vertical distributions elicited by novelty and brain oxidative stress were utilized to determinate behavioral and biochemical alterations elicited by indomethacin treatment, respectively. RESULTS: Our results showed that treatment with indomethacin 3 mg/kg induces animal death. No changes in animal survival were observed in animals treated with lower doses of indomethacin. Indomethacin induced significant anxiogenic-like behavior as well as intense oxidative stress in zebrafish brain. Treatment with alpha-tocopherol was able to prevent anxiety-like behavior and brain oxidative stress induced by indomethacin. CONCLUSIONS: Data presented in current study demonstrated for the first time that indomethacin induces anxiety-like behavior mediated by brain oxidative stress in zebrafish as well as that pre-treatment with alpha-tocopherol is able to prevent these collateral effects.

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Infecções odontogênicas são processos patológicos de grande importância na rotina odontológica. Seu tratamento pode constituir um desafio para profissionais e ser motivo de muita discussão. Anti-inflamatórios para casos de infecção severa são rotineiramente utilizados por alguns profissionais para amenizar sintomas agudos, como dor, edema, trismo, disfagia, disfonia e dispneia. Porém, alguns estudos indicam desvantagens do uso desses medicamentos no tratamento das infecções. Uma revisão da literatura foi realizada com o objetivo de responder se indivíduos acometidos por infecção odontogênica grave apresentam melhora do quadro com o emprego de anti-inflamatórios não-esteroidais ou esteroidais quando se avalia tempo de internação hospitalar, dor, edema, trismo, entre outros aspectos. Em dezembro de 2023, a base de dados eletrônicos PubMed/MEDLINE foi acessada e termos específicos indexados no Mesh e DeCS foram utilizados para a busca. Poderiam ser incluídos estudos observacionais, ensaios clínicos ou revisões que correspondessem à pergunta foco. Ao fim do processo de seleção de artigos, quatro foram incluídos. Outros dois artigos foram encontrados em lista de referências de artigos primariamente selecionados. Um estudo transversal relatou agravos em infecções odontogênicas entre paciente que fizeram uso de anti-inflamatórios. Um segundo e um terceiro estudos transversais não relataram diferenças nos desfechos quando compararam o uso e o não uso de anti-inflamatórios. Porém, o segundo detectou um maior consumo de antibióticos por aqueles pacientes que foram medicados com anti-inflamatórios. Uma auditoria reportou baixo índice de prescrição de corticoides no tratamento de infecções odontogênicas em rotinas de centros de saúde, exceto em casos de severidade, como na presença de dispneia e disfagia. Uma revisão que objetivou relatar o uso de anti-inflamatórios em infecções odontogênicas, não sugeriu qualquer influência desses medicamentos no tratamento. Por último, uma revisão sistemática incluiu pesquisas e relatos de caso que avaliaram os efeitos de corticoides em infecções profundas em espaços cervicais, epiglotite, supraglotite, celulite orbitária e periorbitária, faringite e abscesso peritonsilar. Resultados positivos foram encontrados, porém nenhum dos estudos incluídos relataram desfechos baseados em infecções odontogênicas. Portanto, sugere-se que o uso de anti-inflamatórios pode ocultar sinais inflamatórios da infecção, retardando seu correto diagnóstico e tratamento, resultando um prognóstico não favorável. Corticoides em alta dose por curto período de tempo é visto como adjuvante no tratamento de infecções cervicofaciais severas, principalmente quando vias aéreas estão comprometidas.

Odontogenic infections are pathologic processes of great importance in the dentistry routine. Its treatment may be a challenge for professionals and it may be the subject of discussion. Usually, some professionals prescribe anti-inflammatories for severe cases of infection to alleviate acute symptoms, such as pain, edema, trismus, dysphagia, dysphonia, and dyspnea. However, some studies indicate disadvantages of using these medications to treat infections. A review of the literature was conducted to answer whether individuals affected by severe odontogenic infection improve their condition with the use of non-steroidal or steroidal anti-inflammatory drugs when evaluating length of hospitalization, pain, edema, trismus, among others aspects. In December 2023, the electronic database PubMed/MEDLINE was accessed and specific terms indexed in the Mesh were used for the search. Observational studies, clinical trials or reviews that correspond to the focus question could be included. At the end of the article selection process, four studies were included. Two other articles were found in the reference list of primarily selected articles. A cross-sectional study reported worsening of odontogenic infections among patients who used anti-inflammatories. A second and third cross-sectional studies reported no differences in outcomes when comparing the use and non-use of anti-inflammatories. However, the second detected a greater consumption of antibiotics by those who were treated with anti-inflammatories. An audit reported a low rate of prescription of corticosteroids in the treatment of odontogenic infections in the routine of dental offices, except in severe cases, such as in the presence of dyspnea and dysphagia. A review that aimed to report the use of anti-inflammatories in odontogenic infections did not suggest any influence of these medications on the treatment. Finally, a systematic review included researches and case reports that evaluated the effects of corticosteroids on deep neck infections, epiglottitis, supraglottitis, orbital and periorbital cellulitis, pharyngitis and peritonsillar abscess. Positive results were found, but none of the included studies reported outcomes based on odontogenic infections. Therefore, it is suggested that the use of anti-inflammatory drugs may hide inflammatory signs of the infection, delaying its correct diagnosis and treatment, resulting in an unfavorable prognosis. High-doses corticosteroids for a short period of time are seen as an adjuvant in the treatment of severe cervicofacial infections.

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Among the biological targets extensively investigated to improve inflammation and chronic inflammatory conditions, cyclooxygenase enzymes (COXs) occupy a prominent position. The inhibition of these enzymes, essential for mitigating inflammatory processes, is chiefly achieved through Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). In this work, we introduce a novel method-based on computational molecular docking-that could aid in the structure-based design of new compounds or the description of the anti-inflammatory activity of already-tested compounds. For this, we used eight crystal complexes (four COX-1 and COX-2 each), and each pair had a specific NSAID: Celecoxib, Meloxicam, Ibuprofen, and Indomethacin. This selection was based on the ligand selectivity towards COX-1 or COX-2 and their binding mode. An interaction profile of each NSAID was compiled to detect the residues that are key for their binding mode, highlighting the interaction made by the Me group. Furthermore, we rigorously validated our models based on structural accuracy (RMSD < 1) and (R2 > 70) using eight NSAIDs and thirteen compounds with IC50 values for each enzyme. Therefore, this model can be used for the binding mode prediction of small and structurally rigid compounds that work as COX inhibitors or the prediction of new compounds that are designed by means of a structure-based approach.

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Background: Fixed erythema pigmento (FPE) is an allergic drug reaction, the pathophysiology of which is not exactly known. It is more common in women with location on the face. Clinical presentation: round or oval red-purple macule, well defined, with swelling, pain, itching, and burning. Diagnosis is clinical, oral chal- lenge is contraindicated due to possible severe reaction. On withdrawal of the drug, residual violaceous hyperpigmentation remains. Case report: 34-year-old female diagnosed with allergic rhinitis and asthma. She received treatment with ibuprofen and cephalexin 1 month ago due to dental infection. For the past 2 weeks, she has presented dermatological lesions characterized by hyperpigmentation under the lower eyelids, accompanied by pain, burning, and itching. On physical examination, well-defined red-purple pigmentation was observed in both periocular regions. The challenge test is not justified, the clinical history is the diagnostic pillar. The indication is to stop the medication immediately and continue monitoring. Conclusions: EPF is a drug reaction related to drug use. It creates a challenge for diagnosis due to poor knowledge of the characteristics of the dermatosis and poor clinical and pharmacological questioning. The EPF approach requires knowing the clinical characteristics of this dermatosis, making a differential diagnosis with other lesions and indicating the suspension of the responsible medication.

Antecedentes: El eritema pigmentado fijo (EPF) es una reacción alérgica medicamentosa, de la cual no se conoce con exactitud la fisiopatología. Es más frecuente en la mujer con localización en la cara. Presentación clínica: mácula redonda u oval de color rojo-violáceo, bien delimitada, con edema con dolor, prurito y ardor. El diagnóstico es clínico, contraindicado el reto oral por posible reacción grave. Al retirar el fármaco, queda una hiperpigmentación residual violácea. Reporte de caso: Femenina de 34 años con diagnóstico de rinitis alérgica y asma, Recibió tratamiento con Ibuprofeno y cefalexina hace 1 mes debido a proceso infeccioso dental. Desde hace 2 semanas presenta lesiones dermatológicas caracterizadas por hiperpigmentación debajo de párpados inferiores, acompañado de dolor, ardor y prurito. A la exploración física en ambas regiones perioculares se observa pigmentación bien delimitada rojo-violáceo. La prueba de reto no se justifica, la historia clínica es el pilar diagnóstico. La indicación es suspender el medicamento de inmediato y vigilancia continua. Conclusiones: El EPF es una reacción a medicamentos relacionada con el consumo de fármacos. Genera un desafío para el diagnóstico debido al pobre conocimien- to de las características de la dermatosis y un deficiente interrogatorio clínico y farmacológico. El abordaje del EPF requiere conocer las características clínicas de esta dermatosis, realizar el diagnostico diferencial con otras lesiones e indicar la suspensión del medicamento responsable.

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The consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have increased significantly in the last years (2020-2022), especially for patients in COVID-19 treatment. NSAIDs such as diclofenac, ibuprofen, and paracetamol are often available without restrictions, being employed without medical supervision for basic symptoms of inflammatory processes. Furthermore, these compounds are increasingly present in nature constituting complex mixtures discarded at domestic and hospital sewage/wastewater. Therefore, this review emphasizes the biodegradation of diclofenac, ibuprofen, and paracetamol by pure cultures or consortia of fungi and bacteria at in vitro, in situ, and ex situ processes. Considering the influence of different factors (inoculum dose, pH, temperature, co-factors, reaction time, and microbial isolation medium) relevant for the identification of highly efficient alternatives for pharmaceuticals decontamination, since biologically active micropollutants became a worldwide issue that should be carefully addressed. In addition, we present a quantitative bibliometric survey, which reinforces that the consumption of these drugs and consequently their impact on the environment goes beyond the epidemiological control of COVID-19.

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Mesenchymal stromal cell (MSC)-derived products, such as trophic factors (MTFs), have anti-inflammatory properties that make them attractive for cell-free treatment. Three-dimensional (3D) culture can enhance these properties, and large-scale expansion using a bioreactor can reduce manufacturing costs. Three lots of MTFs were obtained from umbilical cord MSCs produced by either monolayer culture (Monol MTF) or using a 3D microcarrier in a spinner flask dynamic system (Bioreactor MTF). The resulting MTFs were tested and compared using anti-inflammatory potency assays in two different systems: (1) a phytohemagglutinin-activated peripheral blood mononuclear cell (PBMNC) system and (2) a lipopolysaccharide (LPS)-activated macrophage system. Cytokine expression by macrophages was measured via RT-PCR. The production costs of hypothetical units of anti-inflammatory effects were calculated using the percentage of TNF-α inhibition by MTF exposure. Bioreactor MTFs had a higher inhibitory effect on TNF (p < 0.01) than monolayer MTFs (p < 0.05). The anti-inflammatory effect of Bioreactor MTFs on IL-1ß, TNF-α, IL-8, IL-6, and MIP-1 was significantly higher than that of monolayer MTFs. The production cost of 1% inhibition of TNF-α was 11-40% higher using monolayer culture compared to bioreactor-derived MTFs. A 3D dynamic culture was, therefore, able to produce high-quality MTFs, with robust anti-inflammatory properties, more efficiently than monolayer static systems.

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Objetivo: Determinar los hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante diferentes patologías pulpares previos al tratamiento en- dodóntico en Argentina. Materiales y métodos: Se diseñó una encuesta para evaluar la prescripción de antibióticos, tipo de antibióticos, tiempo de prescripción, indicación de antinflamatorios no es- teroides y esteroides ante diferentes patologías pulpares. Se envió a 635 odontólogos especialistas y no especialistas en endodoncia a través de SurveyMonkey. Por medio de la prue- ba de Chi cuadrado se evaluaron las diferencias de medica- ción entre los grupos estudiados. Resultados: En pulpitis se medicó con antibióticos en el 3,48% de los casos y con antinflamatorios en un 62,60%. En necrosis pulpar sin fístula no se indicó ninguna medica- ción en un 64,47% de los casos, seguido de antibióticos en un 24,56%. En necrosis con fístula, el 52,38% no indicó nin- guna medicación, seguido de medicación con antibióticos en un 35,49%. En periodontitis apical aguda la principal medica- ción fue con antinflamatorios (52,79%), seguido de antibió- ticos (32,87%); y en el absceso alveolar agudo, un 57,10% indicó antibióticos seguido de antinflamatorios. El antibiótico de elección fue la penicilina en un 65,23% de los casos, y en caso de alergia a la misma, el antibiótico elegido fue azitromi- cina (30,12%). El tiempo de prescripción fue de 7 días. En la comparación entre especialistas y no especialistas hubo dife- rencias estadísticamente significativas para pulpitis y necrosis con fístula (p<0,01) y no las hubo entre necrosis sin fístula, periodontitis apical aguda y absceso alveolar agudo (p> 0,05). Conclusiones: La penicilina fue el antibiótico de elec- ción de la mayoría de los odontólogos argentinos encuestados junto al ibuprofeno como anti-inflamatorio. Existiría una so- bremedicación en patologías endodónticas que podría contri- buir a la resistencia microbiana a los antibióticos (AU)

Aim: Determine the systemic medication habits of den- tists specialists and non-specialists in endodontists in differ- ent pulp pathologies prior to root canal treatment in Argen- tina. Materials and methods: A survey was designed to evaluate the prescription of antibiotics, the type of antibiotics, prescription time, indication of non-steroidal anti-inflamma- tory drugs in different pulp pathologies. It was sent to 635 general dentists and endodontic specialists via SurveyMon- key. A Chi-square test was made to evaluate the differences in medication between the studied groups. Results: In pulpitis, antibiotics were prescribed in 3.48% of cases and anti-inflammatories in 62.60%. In pul- pal necrosis without fistula, no medication was indicated in 64.47% of cases, followed by antibiotics in 24.56%. In ne- crosis with fistula, 52.38% did not indicate any medication, followed by medication with antibiotics in 35.49%. In acute apical periodontitis the main medication was anti-inflamma-tories (52.79%), followed by antibiotics (32.87%); and for acute alveolar abscess, 57.10% indicated antibiotics, fol- lowed by anti-inflammatories. The antibiotic of choice was penicillin in 65.23% of the cases, and in case of allergy to it, the chosen antibiotic was azithromycin (30.12%). The prescription time was 7 days. In the comparison between specialists and non-specialists, there were significant dif- ferences for pulpitis and necrosis with fistula (p<0.01) and there were no significant differences between necrosis without fistula, acute apical periodontitis and acute alveo- lar abscess (p>0.05). Conclusions: Penicillin was the antibiotic of choice for the majority of the surveyed Argentine dentists, as well as ibuprofen as an anti-inflammatory drug. These could reflect an overmedication in endodontics pathologies that could con- tribute to microbial resistance to antibiotics (AU)

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