Nonsteroidal Anti-Inflammatory Drugs and Experimental Chagas Disease: An Unsolved Question.

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.

Role for Carboxylic Acid Moiety in NSAIDs: Favoring the Binding at Site II of Bovine Serum Albumin.

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.

Effects of major analgesics on male fertility: A systematic literature review.

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.

Brain oxidative stress mediates anxiety-like behavior induced by indomethacin in zebrafish: protective effect of alpha-tocopherol.

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.

Anti-inflamatórios no tratamento de infecções odontogênicas: revisão da literatura / Anti-inflammatories in the treatment of dental infections: review of the literature

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.

A Computational Method for the Binding Mode Prediction of COX-1 and COX-2 Inhibitors: Analyzing the Union of Coxibs, Oxicams, Propionic and Acetic Acids.

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.

Diclofenac, ibuprofen, and paracetamol biodegradation: overconsumed non-steroidal anti-inflammatories drugs at COVID-19 pandemic.

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.

[Eritema pigmentado fijo secundario a AINE: Reporte de caso].

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.

Comparison of Cost and Potency of Human Mesenchymal Stromal Cell Conditioned Medium Derived from 2- and 3-Dimensional Cultures.

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.

Evaluación de hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante patologías pulpares en Argentina / Evaluation of systemic medication habits of specialists and non-specialists dentists in endodontists in relation to different pulp pathologies in Argentina

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)

Evaluación de hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante patologías pulpares en Argentina / Evaluation of systemic medication habits of specialists and non-specialists dentists in endodontists in relation to different pulp pathologies in Argentina

Resumen Objetivo Determinar los hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante diferentes patologías pulpares previos al tratamiento endodóntico 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 esteroides 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 prueba de Chi cuadrado se evaluaron las diferencias de medicación 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 medicación en un 64,47% de los casos, seguido de antibióticos en un 24,56%. En necrosis con fístula, el 52,38% no indicó ninguna medicación, seguido de medicación con antibióticos en un 35,49%. En periodontitis apical aguda la principal medicación fue con antinflamatorios (52,79%), seguido de antibióticos (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 azitromicina (30,12%). El tiempo de prescripción fue de 7 días. En la comparación entre especialistas y no especialistas hubo diferencias 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 elección de la mayoría de los odontólogos argentinos encuestados junto al ibuprofeno como anti-inflamatorio. Existiría una sobremedicación en patologías endodónticas que podría contribuir a la resistencia microbiana a los antibióticos.

Abstract Aim Determine the systemic medication habits of dentists specialists and non-specialists in endodontists in different pulp pathologies prior to root canal treatment in Argentina. Materials and methods A survey was designed to evaluate the prescription of antibiotics, the type of antibiotics, prescription time, indication of non-steroidal anti-inflammatory drugs in different pulp pathologies. It was sent to 635 general dentists and endodontic specialists via SurveyMonkey. 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 pulpal necrosis without fistula, no medication was indicated in 64.47% of cases, followed by antibiotics in 24.56%. In necrosis 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-inflammatories (52.79%), followed by antibiotics (32.87%); and for acute alveolar abscess, 57.10% indicated antibiotics, followed 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 differences for pulpitis and necrosis with fistula (p<0.01) and there were no significant differences between necrosis without fistula, acute apical periodontitis and acute alveolar 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 contribute to microbial resistance to antibiotics.

Analgesia perioperatória de gatas submetidas a ovariohisterectomia eletiva - uso preemptivo de carprofeno ou grapiprant / Perioperative analgesia in cats undergoing elective ovariohysterectomy - preemptive use of carprofen or grapiprant

Background: The nonsteroidal anti-inflammatory drugs (NSAIDs) exert their analgesic effect through peripheral inhibition of prostaglandin synthesis and a variety of other peripheral and central mechanisms. However, NSAIDs are associated with some adverse effects, mainly related to the gastrointestinal, renal, and hepatic systems, highlighting the need for research to develop safer drugs. Therefore, the aim of this study was to evaluate the efficacy of preoperative oral administration of carprofen or grapiprant in female cats submitted to elective ovariohysterectomy on the quality of perioperative analgesia and the need for hypnotic and analgesic drugs. Materials, Methods & Results: Thirty-three adult female cats were selected, without defined breed and healthy based on physical examination, routine laboratory analyses (complete blood count, total protein, Heinz body investigation and serum quantification of alanine transaminase [ALT], aspartate transaminase [AST], gamma glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], urea, frutosamine, and glucose) and negative tests for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). After 3 days of adaptation, they were submitted to ovariohysterectomy by celiotomy and randomly allocated into 2 groups according to the preoperative drug used: GCAR [carprofen - 4 mg/kg, VO, 2 h before surgery; n = 11] and GGRA (grapiprant - 2 mg/kg IV, 2 h before surgery; n = 21]. The cats were pre-medicated with acepromazine 0.05 mg/ kg IV and later submitted to general anesthesia with propofol intravenously. Anesthesia was maintained with isoflurane in 100% oxygen. After anesthetic induction, a continuous infusion of remifentanil at a rate of 10 µg/kg/h was initiated. During the transanesthetic period, the parameters of heart rate; respiratory rate; systolic, mean, and diastolic arterial pressure using the oscillometric method; electrocardiogram; rectal temperature; partial pressure of CO2 at the end of expiration: and partial saturation of O2 in hemoglobin were continuously monitored. The evaluation of nociception was based on the changes in the aforementioned physiological parameters. The rate of remifentanil used did not change over time with the use of carprofen. However, animals that received grapiprant required a lower remifentanil dose at 20, 25, and 30 min during the procedure. The female cats that received carprofen showed an increase in mean heart rate at 30 min compared to that at 20 and 25 min. In the Grapiprant group, the heart rate at 35 min was higher only than that observed at 25 min. Discussion: The remifentanil rate did not differ between the groups, even between the times for GCAR. However, the remifentanil rate was lower from 20 min of the procedure for GGRA. This decrease may be related to a decrease in the need for anesthetics and analgesics by decreasing temperature, which causes decreases in metabolism and surgical stimulation. The increase in systolic, mean, diastolic, and heart rate arterial pressure parameters observed in both treatments after 15 min of anesthesia is related to the nociceptive stimulus resulting from traction and ligation of the ovarian pedicles and maneuvers for exteriorization of the uterus. These are considered the moments of greater surgical stimulus during ovariohysterectomy, evidenced by the greater release of cortisol and increase in physiological parameters. The results of this study show that the administration of carprofen or grapiprant was clinically similar when used preemptively for perioperative analgesia in cats submitted to elective ovariohysterectomy.

Effectiveness of the therapeutic laser in the syndrome of dysfunction of the temporomandibular joint of arthrogenic origin / Eficacia del láser terapéutico en el síndrome de disfunción de la articulación temporomandibular de origen artrogénico

Abstract Temporomandibular joint dysfunction syndrome (TMD), is a collective term characterized by symptoms involving chewing muscles, temporomandibular joint and orofacial structures. The efficacy of low intensity laser (LLLT) Gallium arsenide, in combination with a non-steroidal anti-inflammatory drug (NSAID) was evaluated. The main objective was to evaluate the maximum mouth opening without pain (ABM), arthralgia in the joint capsule through visual analog scale (VAS), laterality, protrusion, joint noises and count of tablets ingested per group. A controlled clinical trial (double-blind-randomized) was carried out in 30 subjects, who presented DTM of arthrogenic etiology; 5 applications of LLLT were made with wavelength of 810 nm, output optical power of 100-200 mw, emission PW=Pulsed (1-10,000Hz), dose of 10 jouls-cm², time of 1.44 minutes in mouth closed and with the mouth half open. One more follow-up appointment per month. There were two groups: experimental and control group, where different variables were analyzed (ABM, laterality, protrusion, VAS and sociodemographic). In the control group, a supposed LT application (not active) was made, for later comparison. Pain-free ABM was assessed in all appointments in addition to the other clinical parameters. Repeated measures analysis was performed with mixed models. Thirty patients were included of which 28 finished the treatment, two of them were lost during follow-up. The groups were similar in all their baseline variables. There were no statistically significant differences when applying the final multiple regression analysis, in the ABM, or in any other of the clinical parameters analyzed. LT was not effective in treating arthrogenic DTM.

Resumen El síndrome de disfunción de la articulación temporomandibular (DTM) es un término colectivo caracterizado por síntomas que involucran músculos de la masticación, articulación temporomandibular y estructuras orofaciales. Se evaluó la eficacia del láser de baja intensidad (LLLT) Arseniuro de galio, en combinación con un antiinflamatorio no esteroideo (AINE). El objetivo principal fue evaluar la apertura bucal máxima sin dolor (ABM), la artralgia en cápsula articular a través de escala visual análoga (EVA), lateralidades, protrusión, ruidos articulares y conteo de tabletas ingeridas por grupo. Se realizó un ensayo clínico controlado (doble ciego-aleatorizado) en 30 sujetos, que presentaban DTM de etiología artrogénica; se les realizaron 5 aplicaciones de LLLT con longitud de onda de 810 nm, potencia óptica de salida de 100-200 mw, emisión PW=Pulsed (1-10,000Hz), dosis de10 jouls-cm², tiempo de1.44 minutos a boca cerrada y con la boca semiabierta. Una cita más de seguimiento al mes. Se tuvieron dos grupos: experimental y grupo control, donde se analizaron diferentes variables (ABM, lateralidades, protrusión, EVA y sociodemográficas). En el grupo control se hizo una supuesta aplicación LT (no activo), para posterior comparación. En todas las citas se valoró la ABM sin dolor además de los otros parámetros clínicos. Se realizó análisis de medidas repetidas con modelos mixtos. Se incluyeron 30 pacientes de los cuales 28 finalizaron el tratamiento, dos de ellos se perdieron en el seguimiento. Los grupos fueron similares en todas sus variables basales. No hubo diferencias estadísticas significativas al aplicar los análisis de regresión múltiple finales, en la ABM, ni tampoco en ningún otro de los parámetros clínicos analizados. El LT no fue eficaz en el tratamiento de la DTM de origen artrogénico.

Efectos antirresortivos y antimicrobianos de los antiinflamatorios no esteroideos en lesiones periapicales / Antiresorptive and antimicrobial effects of nonsteroidal anti-inflammatory drugs in periapical lesion

Los antiinflamatorios no esteroideos (AINE) son un grupo de fármacos que han sido comúnmente prescritos por sus propiedades antiinflamato- rias, antipiréticas y analgésicas, mismas que se deben a la inhibición de la formación de prostaglandinas. Este mecanismo ha sido ampliamente respaldado en la literatura; sin embargo, en la actualidad poco se co- noce sobre las propiedades adicionales de estos medicamentos como el efecto antirresortivo y antimicrobiano. La función antirresortiva se debe principalmente al bloqueo de la producción de prostaglandinas en específico la PGE2, que posee gran potencial osteoclastogénico, esencial para la aparición de lesiones periapicales; asimismo, la acción antimicrobiana de los AINE está relacionada con la afectación directa de la perpetuación de biopelícula, potencian la acción de los antibióticos, entre otros. Dichos efectos combinados podrían contribuir en la cura- ción de lesiones periapicales. El objetivo de este estudio es recopilar información actualizada sobre estas funciones agregadas de los AINE, con el fin de dar a conocer a los profesionales estos beneficios en la terapéutica de las lesiones periapicales (AU)

Non-steroidal anti-inflammatory (NSAIDs) are a group of drugs that have been commonly prescribed for their anti-inflammatory, antipyretic and analgesic properties, which are due to the inhibition of prostaglandin formation. This mechanism has been widely supported in the literature; however, currently little is known about the additional properties of these drugs such as the antiresorptive and antimicrobial effect. The antiresorptive function is mainly due to the blockage of prostaglandin production, specifically PGE2, which has great osteoclastogenic potential, and is essential for the appearance of periapical lesions; likewise, the antimicrobial action of NSAIDs is related to the fact that they directly affect the perpetuation of biofilms, enhance the action of antibiotics, among others. These combined effects could contribute to the healing of periapical lesions. The aim of this study is to gather updated information on these added functions of NSAIDs, in order to inform professionals about these benefits in the therapy of periapical lesion (AU)

Natural essential oil mix of sweet orange peel, cumin, and allspice elicits anti-inflammatory activity and pharmacological safety similar to non-steroidal anti-inflammatory drugs.

An inflammation response occurs when the body reacts to exogenous and endo enous noxious stimuli, and it helps the body respond to infection and repair tissues, adapt to stress, and remove dead or damaged cells. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs are traditionally used to treat inflammation; however, these drugs often cause negative side effects. For this reason, developing and establishing effective alternative medicines for treating many chronic diseases with underlying inflammation is critically dependent on the identification of new organic molecules and bioactive substances. Aromatic and volatile compounds found in essential oils isolated from Pimenta dioica (allspice), Cuminum cyminum (cumin), and Citrus sinensis (sweet orange) are a source of bioactive compounds. Allspice essential oil reduces ear inflammation more than 65% and the anti-inflammatory activity of allspice essential oil is enhanced when combined with sweet orange peel and cumin essential oils, resulting in the reduction of edema inflammation by more than 85%, similar to indomethacin. As an alternative to anti-inflammatory treatment, essential oil mix is pharmacologically safe as it is neither toxic nor mutagenic.

Echinodorus macrophyllus fraction with a high level of flavonoid inhibits peripheral and central mechanisms of nociception.

BACKGROUND AND AIM: Echinodorus macrophyllus (Kunth.) Micheli is popularly used for acute and chronic inflammatory conditions. The anti-inflammatory activity was previously demonstrated for its flavonoid-enriched fractions. The aim of this work assessed the antinociceptive properties of both aqueous extract and its fractions. EXPERIMENTAL PROCEDURE: The antinociceptive activity was determined by acetic acid-induced writhing, formalin test, tail immersion test, hot-plate test, xylene-induced ear edema methods, and the evaluation of its mechanism was performed in the writhing model. The aqueous extract of Echinodorus macrophyllus (AEEm) was fractionated, yielding Fr20, and Fr40. Fr40 composition was determined by HPLC-DAD-ESI-MS. RESULTS AND CONCLUSION: Fr20 (all doses) and Fr40 (100 mg/kg) reduced the nociception in the tail-flick model. Both fractions increased the percentage of maximum possible effect with 25 mg/kg, in the hot-plate assay, at 60 min, while AEEm reduced pain only with 50 and 100 mg/kg. There was a reduction in xylene-edema index, with Fr40 (25 mg/kg), AEEm (50 mg/kg) and Fr20 (50 mg/kg). All doses of AEEm, Fr20, and Fr40 reduced both phases of the formalin model. In the abdominal contortion model, Fr40 presented the highest activity, reducing 96% of contortions and its antinociceptive mechanism was evaluated. The results indicated the involvement of NO and adrenergic activation pathways. The main components of Fr40 are swertisin, swertiajaponin, isoorientin 7,3'-dimethyl ether, swertisin-O-rhamnoside, isoorientin, isovitexin, isovitexin-Orhamnoside, and isovitexin-7-O-glucoside. The aqueous extract of E. macrophyllus leaves and its fractions exhibited significant analgesic effect, mediated through both peripheral and central mechanisms being considered a potentially antinociceptive drug.

Mecanismo de los AINES y antiinflamatorios derivados para el control del dolor y la inflamación. Uso de antiinflamatorios en odontología / Mechanism of NSAIDs and derived drugs for pain and inflammation control. Use of anti-inflammatories in odontology

Las urgencias odontológicas son, quizá, las razones principales de atención en el consultorio, muchas veces el significado de dolor se encuentra acompañado por inflamación; el uso de antiinflamatorios no esteroideos (AINES) es común en el ejercicio de la odontología por la excelente respuesta analgésica y antiinflamatoria que tiene, por lo que es importante conocer la fisiopatología de la inflamación y el dolor y cómo actúan los AINES, ya que algunos de estos fármacos tienen respuestas adversas y sitios de acción importantes. Los factores de riesgo por inflamación y dolor nos obligan a conocer la variedad de fármacos que no entran en la clasificación de AINES y que tenemos a disposición, hay más opciones para la elección ante la presencia de inflamación por un factor en particular, cada uno de éstos tienen indicaciones y contraindicaciones que conoceremos, lo cual nos ampliará el conocimiento para dar una prescripción ante la presencia de eventos inflamatorios. Se realizó un estudio detallado de artículos bibliográficos de cada tema, los fármacos más usados en odontología son los AINES, hay poco uso y conocimiento de antiinflamatorios que podemos usar en urgencias, el porcentaje de uso de los AINES derivados del ácido propiónico es alto por la excelente respuesta en pacientes y otras veces por el desconocimiento de más opciones (AU)

Dental emergencies are perhaps the main reasons for care in the office, many times the meaning of pain is accompanied by inflammation, the use of non-steroidal anti-inflammatory drugs is common in the practice of dentistry due to the excellent analgesic and anti-inflammatory response it has, important is knowing the pathophysiology of inflammation and pain, how NSAIDs act, some of these drugs have adverse responses and important sites of action, risk factors for inflammation and pain require us to know the variety of drugs that do not enter the classification of NSAIDs and we have at our disposal, there are more options for choosing in the presence of inflammation due to a particular factor, each of these have indications and contraindications that we will know, it expands our knowledge to give a prescription in the presence of inflammatory events. A detailed study of bibliographic articles on each topic was carried out, the drugs most used in dentistry are NSAIDs, there is little use and knowledge of anti-inflammatories that we can use in the emergency room, the percentage of use of NSAIDs derived from propionic acid is high, due to the excellent response in patients and others due to lack of knowledge of more options (AU)

First case report of Ctenus medius envenomation: Clinical features of a patient bitten three times by the same spider.

A 22 years old undergraduate student was injured three times by a C. medius spider while wearing pants. Right foot and internal lower leg were bitten in three sites, leading to local pain and oedema, besides a total leg paresthesia as immediate symptoms. A series of photographs of the sites were taken since day 0 until resolution in day 10. Two hours after the accident, the victim received intravenous promethazine. Despite cessation of pain and paresthesia after 24 hours, an intense erythema and itching emerged reaching the maximum in day 4, when the victim returned to hospital and received topic dexamethasone and oral dexchlorpheniramine. The regression was complete in day 10. This accident opened room for discussion of empiric drug choice for immediate and subsequent symptoms of unknown envenomations, as good as a reference for further accidents with this common spider. Biological aspects such as venom composition and spider control of delivered venom amount are also discussed.

Promising Hybrids Derived from S-Allylcysteine and NSAIDs Fragments against Colorectal Cancer: Synthesis, In-vitro Evaluation, Drug-Likeness and In-silico ADME/tox Studies.

We synthesized twelve hybrids, S-allyl Cysteine methyl, ethyl and propyl ester-based non-steroidal anti-inflammatory drugs and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of all compounds was evaluated against SW480 human colon adenocarcinoma cells and the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 10b-c, 11b and 12b displayed the best anticancer activity with IC50 values between 0.131-0.183 mM and selectivity indices higher than 1 after 48 h of treatment. Selectivity indices were comparable to those reported for the reference drug, 5-fluorouracil (SI > 1). The SAR analysis showed that compounds with two carbon atom alkylic chains displayed the best activity (10b, 11b and 12b). Modeling studies including drug-likeness, bioactivity score and ADME/tox studies using online tools like molinspiration and Osiris suggested that these designed hybrids have a good pharmacological profile and can be considered as promising scaffolds for further studies in the search for new therapeutic alternatives to treat colorectal cancer.