Prescription of non-steroidal anti-inflammatory and antirheumatic drugs in outpatient hypertensive patients.

BACKGROUND: It has been documented that NSAIDs (nonsteroidal anti-inflammatory and antirheumatic drugs) reduce the effectiveness of some antihypertensive drugs. OBJECTIVE: Analyze the prescription of NSAID and the variables associated in outpatients with hypertension and explore some characteristics of the physicians. MATERIAL AND METHODS: Cross-sectional study, included patients with hypertension from the Family Medicine Unit No. 24 in Mante, Tamaulipas. From the patients, sociodemographic data, clinical history and pharmacological treatments were obtained. From the physicians, sociodemographic and academic information were collected. RESULTS: Mean age of the patients was 63 ± 11 years and 31.7% were prescribed NSAIDs. When compare exposed versus non-exposed to NSAIDs, being in uncontrolled high blood pressure, uncontrolled hypertension, multimorbidity and polypharmacy. The variables associated to the prescription of NSAIDs were: uncontrolled hypertension, multimorbidity and polypharmacy. The 56.7% of the physicians were women, 83.3% with experience >10 years and 33.3% with current certification by the Council in Family Medicine. CONCLUSIONS: The inappropriate prescription of NSAIDs revealed the need to implement actions to mitigate the potential risk for the hypertension patients to present a complication.

ANTECEDENTES: Los antiinflamatorios y los antirreumáticos no esteroideos (AINE) disminuyen la eficacia de algunos antihipertensivos. OBJETIVO: Analizar el patrón de prescripción de AINE y las variables asociadas en pacientes ambulatorios con diagnóstico de hipertensión arterial, así como explorar algunas características de los médicos prescriptores. MATERIAL Y MÉTODOS: Estudio transversal de pacientes con hipertensión de la Unidad de Medicina Familiar 24 en Ciudad Mante, Tamaulipas. De los pacientes se registraron datos sociodemográficos, antecedentes patológicos y tratamientos farmacológicos; y de los médicos, información sociodemográfica y académica. RESULTADOS: La edad promedio de los pacientes fue de 63 ± 11 años, 31.7 % recibía AINE y al contrastarlos con quienes no los recibían, se identificó mayor proporción de obesidad, presión arterial más elevada, más casos en descontrol de la hipertensión arterial, multimorbilidad y polimedicación. Las variables asociadas a la prescripción de AINE fueron estar en descontrol de la hipertensión arterial, multimorbilidad y polimedicación; 56.7 % de los médicos prescriptores fue del sexo femenino, 83.3 % con antigüedad superior a 10 años y 33.3 % con certificación vigente. CONCLUSIONES: La prescripción inapropiada de AINE reveló la necesidad de implementar acciones para mitigar el riesgo potencial de los pacientes hipertensos de presentar una complicación.

Priority list of pharmaceutical active compounds in aquatic environments of Mexico considering their occurrence, environmental and human health risks.

Pharmaceutical active compounds (PhACs) are detected pollutants in aquatic environments worldwide at concentrations ranging from ng L-1 to µg L-1. Currently, PhAC monitoring is poorly realized in Mexico. This study proposes a priority list of PhACs in Mexican aquatic environments, considering their occurrence and environmental and human health risks. Ecological risks were assessed as Risk Quotients (RQ) values using the PhAC concentrations detected in surface water, obtaining high risks (RQ > 1) against aquatic organisms, especially of naproxen, ibuprofen, diclofenac, acetaminophen, 17ß-estradiol, carbamazepine, ketoprofen, caffeine. In contrast, potential human health risks (RQH) were assessed on the Mexican population using the concentrations quantified in groundwater, demonstrating potential risks (RQH > 0.2) on the population, particularly of DCF and CBZ. Thus, a priority list of PhACs can be used as a reference for environmental monitoring in Mexican water supplies as well as PhACs monitoring in countries of the Caribbean region and Central America.

Inflammation and cancer: friend or foe?

Chronic inflammation plays a crucial role in the onset and progression of pathologies like neurodegenerative and cardiovascular diseases, diabetes, and cancer, since tumor development and chronic inflammation are linked, sharing common signaling pathways. At least 20% of breast and colorectal cancers are associated with chronic inflammation triggered by infections, irritants, or autoimmune diseases. Obesity, chronic inflammation, and cancer interconnection underscore the importance of population-based interventions in maintaining healthy body weight, to disrupt this axis. Given that the dietary inflammatory index is correlated with an increased risk of cancer, adopting an anti-inflammatory diet supplemented with nutraceuticals may be useful for cancer prevention. Natural products and their derivatives offer promising antitumor activity with favorable adverse effect profiles; however, the development of natural bioactive drugs is challenging due to their variability and complexity, requiring rigorous research processes. It has been shown that combining anti-inflammatory products, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and statins, with plant-derived products demonstrate clinical utility as accessible adjuvants to traditional therapeutic approaches, with known safety profiles. Pharmacological approaches targeting multiple proteins involved in inflammation and cancer pathogenesis emerge as a particularly promising option. Given the systemic and multifactorial nature of inflammation, comprehensive strategies are essential for long term success in cancer therapy. To gain insights into carcinogenic phenomena and discover diagnostic or clinically relevant biomarkers, is pivotal to understand genetic variability, environmental exposure, dietary habits, and TME composition, to establish therapeutic approaches based on molecular and genetic analysis. Furthermore, the use of endocannabinoid, cannabinoid, and prostamide-type compounds as potential therapeutic targets or biomarkers requires further investigation. This review aims to elucidate the role of specific etiological agents and mediators contributing to persistent inflammatory reactions in tumor development. It explores potential therapeutic strategies for cancer treatment, emphasizing the urgent need for cost-effective approaches to address cancer-associated inflammation.

Low Frequency of Upper Gastrointestinal Bleeding Despite Non-Steroidal Anti-Inflammatory Drugs and Corticosteroids in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB). OBJECTIVE: This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB. METHODS: A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression. RESULTS: Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (AOR) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an AOR of 6.17 (95% CI 1.79- 21.24). CONCLUSION: This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.

[Comparative study to evaluate the effectiveness of treatment with platelet-rich plasma and NSAIDs in grade I-II gonarthrosis]. / Estudio comparativo para evaluar la efectividad del tratamiento con plasma rico en plaquetas y con AINEs en la gonartrosis grado I-II.

INTRODUCTION: population aging is a worldwide demographic phenomenon of the last thirty years. This increase in life expectancy leads to an increase in the incidence of degenerative diseases, mainly gonarthrosis. According to World Health Organization (WHO) estimates, 10% of the population over 60 years of age suffers from osteoarthrosis, and 40% of the population over 70 years of age suffers from gonarthrosis, figures that could increase in the next decade. Approximately 80% of people over 65 years of age present radiographic changes with evidence of gonarthrosis, being 10-25% of the reason for medical visits at the first level of care. Treatment with intra-articular platelet rich plasma has proven to be an effective therapeutic alternative. MATERIAL AND METHODS: a prospective, quasi-experimental, non-randomized study was carried out to compare the behavior of grade I and II gonarthrosis in 140 patients diagnosed clinically and radiologically. Separated into two groups of patients, the first group treated with non-steroidal anti-inflammatory drugs (NSAIDs) and the second group treated with intra-articular infiltration with platelet-rich plasma (PRP). The same was carried out in the Specialties Clinic No. 3 of the Cuauhtémoc Health Jurisdiction, in the orthopedics office during the year 2020. Descriptive statistics were analyzed through the elaboration of a frequency table that allowed us to calculate the mean and standard deviation, and inferential statistics were analyzed through the 2 test. RESULTS: the age group most affected by gonarthrosis is 60 to 69 years of age with 43.5% of the total number of patients, being the female sex the most affected with 33.5%. Most of the patients had a body mass index that placed them as overweight and obese with 39 and 53% respectively. Pain evolved towards improvement in 92% of patients treated with platelet-rich plasma (PRP) and in 25.7% of patients treated with nonsteroidal anti-inflammatory drugs. The functional capacity of the knee joint recovered in 97% of the patients treated with PRP and in 35.7% of those treated with nonsteroidal anti-inflammatory drugs. CONCLUSIONS: treatment of grade I and II gonarthrosis with intra-articular platelet-rich plasma is more effective than treatment with non-steroidal anti-inflammatory drugs.

INTRODUCCIÓN: el envejecimiento poblacional es un fenómeno demográfico a nivel mundial de los últimos 30 años. Dicho aumento de la expectativa de vida conlleva a un incremento en la incidencia de enfermedades degenerativas, principalmente de gonartrosis. Según cálculos de la Organización Mundial de la Salud (OMS), se estima que 10% de la población mayor de 60 años padece de osteoartrosis, 40% de la población mayor de 70 años presenta gonartrosis, cifras que podrían aumentar en la siguiente década. Aproximadamente 80% de las personas mayores de 65 años presentan cambios radiográficos con evidencia de gonartrosis, siendo 10-25% del motivo de visita médica en el primer nivel de atención. El tratamiento con plasma rico en plaquetas intraarticular ha demostrado ser una alternativa terapéutica eficaz. MATERIAL Y MÉTODOS: se realizó un estudio prospectivo, cuasiexperimental, no aleatorizado donde se comparó el comportamiento de la gonartrosis grado I y II en 140 pacientes diagnosticados clínica y radiológicamente. Separados en dos grupos de pacientes: primer grupo tratado con antiinflamatorios no esteroideos (AINEs) y el segundo grupo tratado con infiltración intraarticular con plasma rico en plaquetas (PRP). El mismo se llevó a cabo en la Clínica de Especialidades No. 3 de la Jurisdicción Sanitaria Cuauhtémoc, en la consulta de ortopedia durante el año 2020. La estadística descriptiva se analizó a partir de la elaboración de una tabla de frecuencias que permitió calcular la media y la desviación estándar, de igual manera la estadística inferencial se analizó a través de la 2. RESULTADOS: el grupo de edad más afectado por gonartrosis es el de 60 a 69 años de edad con 43.5% del total de pacientes, siendo el sexo femenino el más afectado con 33.5%. La mayoría de los pacientes presentaron índice de masa corporal que los ubicaba como sobrepeso y obesos con 39 y 53%, respectivamente. El dolor evolucionó hacia una mejoría en 92% de los pacientes tratados con plasma rico en plaquetas y en 25.7% de los pacientes tratados con antiinflamatorios no esteroideos. La capacidad funcional de la articulación de la rodilla se recuperó en 97% de los pacientes tratados con plasma rico en plaquetas y en 35.7% de los tratados con antiinflamatorios no esteroideos. CONCLUSIONES: el tratamiento de la gonartrosis grado I y II con plasma rico en plaquetas intraarticular es más efectivo que el tratamiento con antiinflamatorios no esteroideos.

Indomethacin Induces Spermidine/Spermine-N1-Acetyltransferase-1 via the Nucleolin-CDK1 Axis and Synergizes with the Polyamine Oxidase Inhibitor Methoctramine in Lung Cancer Cells.

Indomethacin is a non-selective NSAID used against pain and inflammation. Although cyclooxygenase (COX) inhibition is considered indomethacin's primary action mechanism, COX-independent ways are associated with beneficial effects in cancer. In colon cancer cells, the activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) is related to the increase in spermidine/spermine-N1-acetyltransferase-1 (SSAT-1), a key enzyme for polyamine degradation, and related to cell cycle arrest. Indomethacin increases the SSAT-1 levels in lung cancer cells; however, the mechanism relying on the SSAT-1 increase is unclear. Thus, we asked for the influence of the PPAR-γ on the SSAT-1 expression in two lung cancer cell lines: H1299 and A549. We found that the inhibition of PPAR-γ with GW9662 did not revert the increase in SSAT-1 induced by indomethacin. Because the mRNA of SSAT-1 suffers a pre-translation retention step by nucleolin, a nucleolar protein, we explored the relationship between indomethacin and the upstream translation regulators of SSAT-1. We found that indomethacin decreases the nucleolin levels and the cyclin-dependent kinase 1 (CDK1) levels, which phosphorylates nucleolin in mitosis. Overexpression of nucleolin partially reverts the effect of indomethacin over cell viability and SSAT-1 levels. On the other hand, Casein Kinase, known for phosphorylating nucleolin during interphase, is not modified by indomethacin. SSAT-1 exerts its antiproliferative effect by acetylating polyamines, a process reverted by the polyamine oxidase (PAOX). Recently, methoctramine was described as the most specific inhibitor of PAOX. Thus, we asked if methoctramine could increase the effect of indomethacin. We found that, when combined, indomethacin and methoctramine have a synergistic effect against NSCLC cells in vitro. These results suggest that indomethacin increases the SSAT-1 levels by reducing the CDK1-nucleolin regulatory axis, and the PAOX inhibition with methoctramine could improve the antiproliferative effect of indomethacin.

Ursolic acid-rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease.

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 µg/mL; LC50 26.73 ± 1.2 µg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.

Sodium Salicylate as Feed Additive in Broilers: Absence of Toxicopathological Findings.

Antimicrobial growth promoters (AGPs) in animal production have been related to the increase in multidrug-resistant bacteria. The AGP ban in many countries has highlighted the growing need for alternatives for feed additives. Considering the non-antibiotic anti-inflammatory theory of AGPs, chicks received three different doses of sodium salicylate (SS) in feed (10, 30, 90 mg/kg), basal diet (BD) was used as a negative control, and zinc bacitracin (ZB) was used as a positive control. Chicks were individually housed to increase the accuracy of the dose of SS ingested. Performance parameters and footpad dermatitis were evaluated weekly, while haematology, serum biochemistry, histopathology, and tibial dyschondroplasia were determined on Days 21 and 42. A linear dose-dependent decrease in haemoglobin concentration was observed, but the values were within the normal reference range. Among all the other evaluated parameters, no relevant differences between treatments were observed; however, not even the AGP group performed better than the control group. It is possible that the conditions in which the birds were raised were not stressful enough to allow for anti-inflammatories to demonstrate their beneficial effects on performance. Studies should be conducted where the animals are exposed to commercial conditions, as the presence of natural stressors could allow a better evaluation of the efficacy of the anti-inflammatory agent as a growth promoter.

Estudio comparativo para evaluar la efectividad del tratamiento con plasma rico en plaquetas y con AINEs en la gonartrosis grado I-II / Comparative study to evaluate the effectiveness of treatment with platelet-rich plasma and NSAIDs in grade I-II gonarthrosis

Resumen: Introducción: el envejecimiento poblacional es un fenómeno demográfico a nivel mundial de los últimos 30 años. Dicho aumento de la expectativa de vida conlleva a un incremento en la incidencia de enfermedades degenerativas, principalmente de gonartrosis. Según cálculos de la Organización Mundial de la Salud (OMS), se estima que 10% de la población mayor de 60 años padece de osteoartrosis, 40% de la población mayor de 70 años presenta gonartrosis, cifras que podrían aumentar en la siguiente década. Aproximadamente 80% de las personas mayores de 65 años presentan cambios radiográficos con evidencia de gonartrosis, siendo 10-25% del motivo de visita médica en el primer nivel de atención. El tratamiento con plasma rico en plaquetas intraarticular ha demostrado ser una alternativa terapéutica eficaz. Material y métodos: se realizó un estudio prospectivo, cuasiexperimental, no aleatorizado donde se comparó el comportamiento de la gonartrosis grado I y II en 140 pacientes diagnosticados clínica y radiológicamente. Separados en dos grupos de pacientes: primer grupo tratado con antiinflamatorios no esteroideos (AINEs) y el segundo grupo tratado con infiltración intraarticular con plasma rico en plaquetas (PRP). El mismo se llevó a cabo en la Clínica de Especialidades No. 3 de la Jurisdicción Sanitaria Cuauhtémoc, en la consulta de ortopedia durante el año 2020. La estadística descriptiva se analizó a partir de la elaboración de una Tabla de frecuencias que permitió calcular la media y la desviación estándar, de igual manera la estadística inferencial se analizó a través de la χ2. Resultados: el grupo de edad más afectado por gonartrosis es el de 60 a 69 años de edad con 43.5% del total de pacientes, siendo el sexo femenino el más afectado con 33.5%. La mayoría de los pacientes presentaron índice de masa corporal que los ubicaba como sobrepeso y obesos con 39 y 53%, respectivamente. El dolor evolucionó hacia una mejoría en 92% de los pacientes tratados con plasma rico en plaquetas y en 25.7% de los pacientes tratados con antiinflamatorios no esteroideos. La capacidad funcional de la articulación de la rodilla se recuperó en 97% de los pacientes tratados con plasma rico en plaquetas y en 35.7% de los tratados con antiinflamatorios no esteroideos. Conclusiones: el tratamiento de la gonartrosis grado I y II con plasma rico en plaquetas intraarticular es más efectivo que el tratamiento con antiinflamatorios no esteroideos.

Abstract: Introduction: population aging is a worldwide demographic phenomenon of the last thirty years. This increase in life expectancy leads to an increase in the incidence of degenerative diseases, mainly gonarthrosis. According to World Health Organization (WHO) estimates, 10% of the population over 60 years of age suffers from osteoarthrosis, and 40% of the population over 70 years of age suffers from gonarthrosis, Figures that could increase in the next decade. Approximately 80% of people over 65 years of age present radiographic changes with evidence of gonarthrosis, being 10-25% of the reason for medical visits at the first level of care. Treatment with intra-articular platelet rich plasma has proven to be an effective therapeutic alternative. Material and methods: a prospective, quasi-experimental, non-randomized study was carried out to compare the behavior of grade I and II gonarthrosis in 140 patients diagnosed clinically and radiologically. Separated into two groups of patients, the first group treated with non-steroidal anti-inflammatory drugs (NSAIDs) and the second group treated with intra-articular infiltration with platelet-rich plasma (PRP). The same was carried out in the Specialties Clinic No. 3 of the Cuauhtémoc Health Jurisdiction, in the orthopedics office during the year 2020. Descriptive statistics were analyzed through the elaboration of a frequency Table that allowed us to calculate the mean and standard deviation, and inferential statistics were analyzed through the χ2 test. Results: the age group most affected by gonarthrosis is 60 to 69 years of age with 43.5% of the total number of patients, being the female sex the most affected with 33.5%. Most of the patients had a body mass index that placed them as overweight and obese with 39 and 53% respectively. Pain evolved towards improvement in 92% of patients treated with platelet-rich plasma (PRP) and in 25.7% of patients treated with nonsteroidal anti-inflammatory drugs. The functional capacity of the knee joint recovered in 97% of the patients treated with PRP and in 35.7% of those treated with nonsteroidal anti-inflammatory drugs. Conclusions: treatment of grade I and II gonarthrosis with intra-articular platelet-rich plasma is more effective than treatment with non-steroidal anti-inflammatory drugs.

Acute Kidney Injury in a Cohort of Critical Illness Patients Exposed to Non-Steroidal Anti-Inflammatory Drugs.

To determine whether non-steroidal anti-inflammatory drug (NSAIDs) exposure prior to intensive care unit (ICU) admission affects the development of acute kidney injury (AKI) with renal replacement therapy (RRT). An administrative database is used to establish a cohort of patients who were admitted to the ICU. The exposure to NSAIDs that the patients had before admission to the ICU is determined. Demographic variables, comorbidities, AKI diagnoses requiring RRT, and pneumonia during the ICU stay are also measured. Multivariate logistic regression and inverse probability weighting (IPW) are used to calculate risks of exposure to NSAIDs for patients with AKI requiring RRT. In total, 96,235 patients were admitted to the ICU, of which 16,068 (16.7%) were exposed to NSAIDs. The incidence of AKI with RRT was 2.71% for being exposed to NSAIDs versus 2.24% for those not exposed (p < 0.001). For the outcome of AKI, the odds ratio weighted with IPW was 1.28 (95% CI: 1.15−1.43), and for the outcome of pneumonia as a negative control, the odds ratio was 1.07 (95% CI: 0.98−1.17). The impact of prior exposure to NSAIDs over critically ill patients in the development of AKI is calculated as 8 patients per 1000 exposures. The negative control with the same sources of bias did not show an association with NSAID exposure.

Orbital compartment syndrome due to periorbital angioedema.

A 68-year-old female presented with an episode of unilateral orbital compartment syndrome due to periorbital angioedema. The patient made a consultation at the general Emergency Room with sudden left periorbital edema and serious diminished ipsilateral visual acuity, with examination detecting orbital compartment syndrome secondary to a probable allergic angioedema after ingestion of ibuprofen. She received treatment with intravenous and oral corticosteroids, achieving a rapid improvement in the condition and clinical follow-up was carried out, with evaluation of the peripapillary retinal nerve fiber layer thickness and computed perimetry. Periorbital angioedema due to ibuprofen can be a cause of orbital compartment syndrome whose diagnosis and treatment must be carried out urgently to prevent permanent visual impairment.

Postoperative Acupuncture is as Effective as Preoperative Acupuncture or Meloxicam in Dogs Undergoing Ovariohysterectomy: a Blind Randomized Study.

Background: Acupuncture has the same analgesic effect as non-steroidal antiinflammatory drugs and opioids. It is challenging to perform preoperative acupuncture in unmanageable animals, while the residual postoperative anesthetic effect facilitates the performance of acupuncture postoperatively. Objectives: To compare preoperative acupuncture or meloxicam versus postoperative acupuncture for postoperative analgesia after ovariohysterectomy. Methods: This is a horizontal prospective positive control blind randomized experimental study. Thirty-six dogs were randomly divided into three groups: GA (preemptive acupuncture), GPA (postoperative acupuncture), and GM (meloxicam 0.2 mg/kg IV preoperatively). After sedation with acepromazine (0.05 mg/kg IM), anesthesia was induced with propofol (5.3 ± 0.3 mg/kg) and maintained with isoflurane/O2. Fentanyl (2 µg/kg, IV) was administered immediately before surgery. Bilateral acupuncture was performed at acupoints Large intestine 4, Spleen 6, and Stomach 36 for 20 minutes, before (GA) or immediately after surgery (GPA). Pain was evaluated by an observer blind to the treatment using the Glasgow scale before and for 24 hours after ovariohysterectomy. Dogs with a score ≥ 6 received rescue analgesia with morphine (0.5 mg/kg IM). Nonparametric data were analyzed by the Kruskal-Wallis test, followed by Dunn's test and parametric data by ANOVA followed by Tukey's test. Results: Two GA and one GPA dogs received rescue analgesia once. Two GM dogs received rescue analgesia and one of those was treated again twice. There were no differences in the number of dogs receiving rescue analgesia between groups (p = 0.80). Conclusion: Postoperative acupuncture was as effective as preoperative acupuncture or meloxicam in female dogs undergoing ovariohysterectomy.

Efficacy of Methylprednisolone Compared to Other Drugs for Pain, Swelling, and Trismus Control after Third Molar Surgery: A Meta-Analysis.

The purpose of this systematic review and meta-analysis was to assess the efficacy of methylprednisolone compared to other drugs to control postoperative complications following third molar surgery. PubMed and Google Scholar were used for article searching. Thereafter, the trials meeting the selection criteria and with high methodological quality, according to the Cochrane Collaboration's risk of bias tool, were included in this study. The inverse variance test and mean difference using the Review Manager Software 5.3 for Windows were used to carry out data analysis. Qualitative analysis shows that methylprednisolone is more effective than NSAIDs, but inferior to dexamethasone, for controlling postoperative complications after third molar removal. The quantitative analysis showed no statistical difference for pain control, while trismus evaluation showed a statistical difference after 7 postoperative days in favor of methylprednisolone, when compared to other drugs. In conclusion, methylprednisolone was more effective for trismus control compared to other drugs after lower third molar surgery.

Grapiprant or carprofen following ovariohysterectomy in the cat: analgesic efficacy, hematological, biochemical and urinalysis evaluation.

OBJECTIVES: This study aimed to compare the analgesic effect between carprofen and grapiprant every 12 or 24 h on postoperative pain in cats undergoing ovariohysterectomy, in addition to the effects on the hematological, biochemical and urinalysis variables. METHODS: A total of 32 female cats were randomly divided into three groups, according to the treatment administered with the first dose given orally 90 mins before surgery, as follows: CAR (cats received 4 mg/kg carprofen, n = 11); GRA1 (cats received 2 mg/kg grapiprant, n = 10); and GRA2 (cats received 2 mg/kg grapiprant q12h, n = 11). Pain was assessed by UNESP-Botucatu Multidimensional Composite Pain Scale (UNESP) and Glasgow Feline Composite Measure Pain Scale (GLASGOW) for cats preoperatively (baseline) and at 1, 3, 6, 8, 12 and 24 h after extubation. Venous blood was collected at baseline, and 12 and 24 h after the administration of carprofen or grapiprant to perform a complete blood count (CBC), the percentage of Heinz bodies and serum biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, creatinine and urea). Urinalysis was performed at baseline and 24 h after extubation. Glucose levels were evaluated at baseline and 1 h postoperatively. RESULTS: Pain scores were not significantly different among groups in both scales, although pain was higher at 3 h in comparison with 24 h in all groups. In the GRA1 and GRA2 groups, 67% (14/21) of cats needed rescue analgesia compared with 18% (2/11) in the CAR group. Glucose increased from baseline to 1 h in the GRA1 and GRA2 groups. None of the CBC, serum biochemistry and urinalysis variables differed among groups. CONCLUSIONS AND RELEVANCE: Grapiprant did not promote adequate analgesia during the first 3 h postoperatively in cats undergoing ovariohysterectomy compared with carprofen, and no benefits were observed by administering grapiprant every 12 h.

Solid Phase Extraction and Simultaneous Chromatographic Quantification of some Non-steroidal Anti-inflammatory Drug Residues; an Application in Pharmaceutical Industrial Wastewater Effluent

Abstract Two sensitive and selective methods were developed for the simultaneous determination of four commonly used non-steroidal anti-inflammatory drugs (NSAIDs), namely; paracetamol (PCM), diclofenac sodium (DCF), ibuprofen (IBP), and indomethacin (IND) in wastewater effluents. The first method used HPLC for the determination of the studied drugs using a mobile phase consisting of phosphate buffer (pH 3.0) and acetonitrile at a flow rate of 1 mL/min. in gradient elution mode and detection at 220 nm. The separation process was performed on BDS Hypersil Cyano column (250 x 4.6 mm, 5 µm). The second method was a TLC-densitometric one which was performed using n-Hexane: ethyl acetate: acetic acid in the ratio (6:3.5:0.5) as a developing system. The proposed chromatographic methods were successfully applied for the selective determination of the four studied drugs in simulated and real pharmaceutical wastewater samples after their solid-phase extraction

Erupção pigmentar fixa à nimesulida comprovada por teste de contato / Fixed pigmented erythema from nimesulide proven by patch testing

A erupção pigmentar fixa (EPF) é uma reação cutânea adversa a drogas relativamente comum, envolvendo cerca de 10% de todas as reações de hipersensibilidade a medicamentos (RHM). Envolve uma reação imunológica não imediata, mediada por células T CD8+ sensibilizadas, relacionada ao mecanismo do tipo IVc na classificação de Gell e Coombs. Um dos grupos mais frequentemente implicados nesse tipo de reação é o dos antiinflamatórios. Relatamos o caso de um homem que, 24 horas após iniciar tratamento com nimesulida para lombalgia, apresentou um quadro de lesões cutâneas tipo máculas eritemato-violáceas bem delimitadas e disseminadas pelo corpo. A nimesulida é um fármaco anti-inflamatório não esteroidal (AINE) pertencente à classe das sulfonanilidas, que atua como inibidor seletivo da enzima da síntese de prostaglandina, a ciclo-oxigenase, inibindo preferencialmente a COX-2. O diagnóstico foi comprovado pela realização do teste de contato, também conhecido como patch test, que traduziu positividade na segunda leitura realizada após 72 horas da sua colocação.

Fixed pigmented erythema (FPE) is a relatively common adverse drug reaction, consisting of approximately 10% of all drug hypersensitivity reactions. It involves a non-immediate immune reaction mediated by sensitized CD8+ T cells and related to the type IVc mechanism in the Gell-Coombs classification. One of the groups most frequently involved in this type of reaction is that of anti-inflammatory drugs. We report the case of a man who, 24 hours after starting treatment with nimesulide for low back pain, presented with well-defined cutaneous lesions consisting of erythematous-violaceous macules and spread throughout the body. Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) belonging to the sulfonanilide class that acts as a selective inhibitor of the prostaglandin synthesis enzyme, cyclooxygenase (COX), preferentially inhibiting COX-2. The diagnosis was confirmed by a patch test, which translated positively in the second reading performed 72 hours after its placement.

Antimicrobial Activity of Non-steroidal Anti-inflammatory Drugs on Biofilm: Current Evidence and Potential for Drug Repurposing.

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs' activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.

Improve cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy: additional beneficial effect found in a controlled clinical trial for prostate cancer therapy.

Inflammation is an essential component of prostate cancer (PCa), and mefenamic acid has been reported to decrease its biochemical progression. The current standard therapy for PCa is androgen deprivation therapy (ADT), which has side effects such as cognitive dysfunction, risk of Alzheimer's disease, and dementia. Published results of in vitro tests and animal models studies have shown that mefenamic acid could be used as a neuroprotector. Objective: Examine the therapeutic potential of mefenamic acid in cognitive impairment used in a controlled clinical trial. Clinical trial phase II was conducted on patients undergoing ADT for PCa. Two groups of 14 patients were included. One was treated with a placebo, while the other received mefenamic acid 500 mg PO every 12hrs for six months. The outcome was evaluated through the Mini-Mental State Examination (MMSE) score at six months. At the beginning of the study, both groups had similar MMSE scores (mefenamic acid vs. placebo: 26.0±2.5 vs. 27.0±2.6, P=0.282). The mefenamic acid group improved its MMSE score after six months compared with the placebo group (27.7±1.8 vs. 25.5±4.2, P=0.037). Treatment with mefenamic acid significantly increases the probability of maintained or raised cognitive function compared to placebo (92% vs. 42.9%, RR=2.2, 95% CI: 1.16-4.03, NNT=2.0, 95% CI: 1.26-4.81, P=0.014). Furthermore, 42.9% of the placebo group patients had relevant cognitive decline (a 2-point decrease in the MMSE score), while in patients treated with mefenamic acid, cognitive impairment was not present. This study is the first conducted on humans that suggests that mefenamic acid protects against cognitive decline.

Multifocal Analysis of Acute Pain After Third Molar Removal.

Background: To analyze the pain modulation capacity profile in a Brazilian population, the relationship between opioid receptor (OPRM1) and Catechol-O-methyltransferase (COMT) 1polymorphisms and pain modulation capacity was determined through preoperative pain modulation tests and acute postoperative pain control evaluation, swelling, and trismus in 200 volunteers undergoing lower third molar removal. Methods: Psychologic and clinical parameters were measured. Patient DNA was sequenced for single nucleotide polymorphisms in OPRM1 and COMT, and the salivary concentration of interleukin (IL)-2 (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was evaluated. Primary outcomes were the influence of all predictors on the fluctuation of pain intensity using a visual analogue scale (VAS), and swelling and trismus on the 2nd and 7th postoperative days. Preoperative pain modulation capacity (CPM), pain catastrophizing scale (PCS), body mass index (BMI), and surgery duration and difficulty were evaluated. Results: Salivary concentration of IFN-γ and IL-2 as well as the duration of surgery influenced the fluctuation of postoperative pain in the VAS, and in the sum of the differences in pain intensity test at 8, 48, and 96 h. BMI influenced swelling, while both BMI and COMT haplotype influenced trismus on the 2nd postoperative day. Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03169127.

A Meta-Analysis of the Analgesic Efficacy of Single-Doses of Ibuprofen Compared to Traditional Non-Opioid Analgesics Following Third Molar Surgery.

The purpose of this systematic review was to determine the analgesic efficacy and adverse effects of ibuprofen in comparison with other traditional non-opioid analgesics after third molar surgery. A total of 17 full texts were identified in PubMed and assessed using the Cochrane Collaboration's risk of bias tool by two independent researchers. The sum of pain intensity differences, total pain relief, the overall evaluation, the number of patients requiring rescue analgesics, and adverse effects were collected. Data were analyzed using the Review Manager Software 5.3. for Windows. A total of 15 articles met the criteria. The qualitative and quantitative analysis showed that ibuprofen is more effective to relieve post-operative dental pain than acetaminophen, meclofenamate, aceclofenac, bromfenac, and aspirin. Moreover, ibuprofen and traditional non-steroidal anti-inflammatory drugs have a similar safety profile. In conclusion, ibuprofen 400 mg appears to have good analgesic efficacy and a safety profile similar to other traditional non-steroidal anti-inflammatory drugs after third molar surgery.