Effective Inhibition of TNF-α/mTOR Axis-Mediated Liver Inflammation and Fibrosis Induced by TAA Using a Combination of Metformin and Resveratrol in Association with the Inhibition of the Profibrotic Gene and Protein Expression

SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.

La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.

Dexmedetomidine versus sufentanil as adjuvants to bupivacaine for brachial plexus block during upper extremity surgery: a randomized clinical trial

Abstract Background: Brachial plexus block (BPB) has been accepted as a reliable alternative for general anesthesia in upper limb surgeries. Adding adjuvant drugs like dexmedetomidine and sufentanil has been shown to have clinical and pharmacologic advantages. In this randomized parallel clinical trial, we aim to compare the effects of these two adjuvants for bupivacaine in BPB. Methods: In this double-blinded study, by using computer-assisted block randomization, 40 patients ranged from 20 to 65 years old and scheduled for elective upper limb surgeries were assigned to two equal study groups (n = 20), receiving 1 mL of 5 μg.mL-1 sufentanil (group S) or 1 mL of 100 μg.mL-1 dexmedetomidine (group D) in adjunction to 30 mL of 0.5% bupivacaine for supraclavicular BPB under the guidance of ultrasonography. Characteristics of local anesthesia and postoperative analgesia were evaluated (n = 40). Results: The duration of blocks significantly improved in group S (sensory: estimated median difference (EMD) [95%CI] = 100.0 [70.0~130.0], p < 0.001; motor: EMD [95%CI] = 120.0 [100.0~130.0], p < 0.001). Group S also had significantly longer postoperative analgesia and lower opioid consumption within 24 hours after the surgery (EMD [95%CI] = 4.0 [3.0~7.0], p < 0.001; EMD [95%CI] = -5.0 [-5.0~-5.0], p < 0.001; respectively). None of the patients showed adverse effects concerning vital signs, nausea, or vomiting. Conclusion: Our study showed that during ultrasound-guided supraclavicular BPB, sufentanil is a fairly better choice than dexmedetomidine as an adjuvant for bupivacaine and can provide preferable sensory and motor blocks. No significant side effects were seen in either of the study groups.

Barreiras enfrentadas pelos enfermeiros na ampliação da inserção do dispositivo intrauterino em pacientes no contexto das Unidades Básicas de Saúde / Challenges faced by nurses in promoting the intrauterine devices insertion among patients in Basic Health Units / Barreras que enfrentan los enfermeros para ampliar la inserción de dispositivos intrauterinos en pacientes en el contexto de las Unidades Básicas de Salud

Objetivo: verificar as barreiras enfrentadas pelos enfermeiros na ampliação da inserção de dispositivo intrauterino (DIU) em pacientes no contexto das Unidades Básicas de Saúde. Metodologia: estudo observacional realizado com 66 enfermeiros da Atenção Primária. O instrumento de coleta foi elaborado por revisão de literatura e validado por especialistas da área da saúde da mulher. A coleta de dados ocorreu de forma remota entre outubro de 2021 e janeiro de 2022. Todas as considerações éticas para pesquisas com seres humanos foram respeitadas. Resultados: observou-se que a maioria não realizou treinamento de inserção de DIU (86,4%), não possuíam experiência de inserção (100%) e nem segurança na técnica (71,2%). Ademais, o DIU não é inserido (83,3%) nas unidades de saúde e, para a inserção, há necessidade de realização de exames (84,8%), como ultrassonografia transvaginal (76,2%), exames de citologia oncótica (92,1%) e teste de gravidez (76,2%). Conclusão: as barreiras observadas neste estudo dificultam o acesso ao DIU na Atenção Primária e afetam os direitos à liberdade, à saúde e ao planejamento reprodutivo. Verificou-se a necessidade da criação de um protocolo assistencial sobre o DIU de cobre e elaboração de uma estratégia de qualificação teórico-prática como forma de ampliação do método e garantia dos direitos sexuais e reprodutivos das mulheres previstos na Constituição Federal.

Objective: to assess the impediments confronted by nurses in the expansion of intrauterine device (IUD) insertion within the context of Basic Health Units.Methodology: an observational study was conducted involving 66 Primary Care nurses. The data collection instrument was formulated through an extensive literature review and subsequently validated by experts specializing in women's health. Data collection transpired remotely between October 2021 and January 2022, adhering to all ethical considerations pertinent to research involving human subjects. Results:findings revealed that a majority of participants had not undergone specific training for IUD insertion (86.4%), lacked practical experience in the procedure (100%), and expressed a lack of confidence in executing the technique (71.2%). Furthermore, the IUD insertion was infrequently performed within health units (83.3%), necessitating ancillary tests, such as transvaginal ultrasound (76.2%), oncotic cytology tests (92.1%), and pregnancy tests (76.2%). Conclusion:the identified barriers in this study impede access to IUDs in Primary Care, thereby encroaching upon fundamental rights related to autonomy, health, and reproductive planning. The study underscores the necessity for the formulation of a comprehensive care protocol concerning the copper IUD and the development of a theoretical-practical training strategy. This strategy aims to broaden the utilization of the method, thereby safeguarding women's sexual and reproductive rights as enshrined in the Federal Constitution.

Objetivo: verificar las barreras que enfrentan los enfermeros en la ampliación de la inserción de dispositivos intrauterinos (DIU) en pacientes en el contexto de Unidades Básicas de Salud. Metodología: estudio observacional realizado con 66 enfermeros de Atención Primaria. El instrumento de recolección fue desarrollado a través de una revisión de la literatura y validado por expertos en el campo de la salud de la mujer. La recolección de datos se realizó de forma remota entre octubre de 2021 y enero de 2022. Se respetaron todas las consideraciones éticas para la investigación con seres humanos. Resultados:se observó que la mayoría no realizó entrenamiento para la inserción del DIU (86,4%), no tenía experiencia en la inserción (100%) y no tenía confianza en la técnica (71,2%). Además, el DIU no se inserta (83,3%) en las unidades de salud y, para su inserción, es necesario realizar pruebas (84,8%), como ecografía transvaginal (76,2%), citología oncótica (92,1%) y test de embarazo. (76,2%). Conclusión:las barreras observadas en este estudio dificultan el acceso a los DIU en Atención Primaria y afectan los derechos a la libertad, la salud y la planificación reproductiva. Era necesario crear un protocolo de atención al DIU de cobre y desarrollar una estrategia de capacitación teórico-práctica como forma de ampliar el método y garantizar los derechos sexuales y reproductivos de las mujeres previstos en la Constitución Federal

Interleukin-37 has A Promising Cardioprotective Effect on Isoproterenol-Induced Myocardial Infarction / La Interleucina-37 tiene un Efecto Cardioprotector Prometedor sobre el Infarto de Miocardio Inducido por Isoproterenol

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.

La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.

Evaluation the Effect of Ginseng Plant Root Extract on Complications of Azathioprine on Ovarian Follicles and TSH, LH and Progesterone Hormones in Rats

Background: The search for herbal remedies has gained significant attention due to chemical drugs’ potentially harmful side effects. Finding plants that can mitigate these adverse effects is crucial for enhancing the well-being of individuals undergoing chemical drug treatments. Aim: Numerous studies have demonstrated the potent antioxidant properties of ginseng. Azathioprine, a widely used drug, has been shown to induce detrimental side effects on various body tissues. Thus, this study aimed to assess the efficacy of ginseng in reducing the harmful effects of azathioprine on ovarian tissue. Materials and Methods: In this study, mice were divided into groups and injected with ginseng root extract and azathioprine. Ovarian weight and histological analysis were conducted to evaluate the number of ovarian follicles and corpus luteum. Furthermore, the levels of FSH, LH, and progesterone in the blood of the study groups were assessed using ELISA. Results: In treatment group 4 (ginseng extract and azathioprine), compared to treatment group 2 (azathioprine only), a significant increase in the weight of both left and right ovaries was observed. Treatment group 4 also exhibited a notable increase (P<0.05) in the number of primordial, primary, and atretic follicles. The concentration of progesterone significantly increased in treatment group 4 compared to treatment group 2 (p<0.01). Conclusion: The findings of this study indicate that azathioprine can have destructive effects on ovarian tissues, while ginseng extract demonstrates the potential to reduce these detrimental side effects. Furthermore, ginseng extract appears to positively regulate FSH and progesterone hormones.

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Cherubism in Saudi population: a rare case report / Querubismo na população Saudi: relato de um caso raro

Cherubism is a rare hereditary benign fibro-osseous disorder characterised by bilateral swelling of the mandible and/or maxilla with varying severity of involvement. It occurs because of dominant mutations in SH3BP2 gene on the chromosome 4p16.3. On radiography cherubic lesions appear as multilocular cystic radiolucencies in the jaw bones giving a soap bubble appearance. These lesions usually heal by themselves by the time the patient attains puberty. Treatment is necessary only in aggressive cases where there is severe facial deformity or vital functions are hampered. Surgical corrections are preferred when the lesion is in its dormant phase. The aim of the present case report is to illustrate a case of cherubism in a 9-year-old Saudi boy which is a very rare occurrence as only 1 case of cherubism has been reported so far in the Saudi Arabian population (AU)

Querubismo é uma desordem fibro-óssea hereditária rara caracterizada por aumento de volume bilateral da mandíbula e/ou maxila com graus variáveis de severidade. Ocorre devido a mutação dominante no gene SH3BP2 no cromossomo 4p16.3. Radiograficamente as lesões de querubismo aparecem como radiolucência multilocular semelhantes a bolhas de sabão nos ossos maxilares. Geralmente as lesões involuem espontaneamente quando o paciente atinge a puberdade. O tratamento se faz necessário apenas nos casos mais agressivos que demonstram deformidade facial severa ou comprometimento de funções vitais. Correções cirúrgicas são preferíveis quando a lesão está na fase dormente. O objetivo do presente relato é ilustrar um caso de querubismo em um paciente de 9 anos da Arábia Saudita, sendo este um evento raríssimo com apenas um outro caso relatado na população da Arábia Saudita (AU)

Safflower seed oil, a rich source of linoleic acid, stimulates hypothalamic neurogenesis in vivo / 대한해부학회지

Adult neurogenesis has been reported in the hypothalamus, subventricular zone and subgranular zone in the hippocamp. Recent studies indicated that new cells in the hypothalamus are affected by diet. We previously showed beneficial effects of safflower seed oil (SSO), a rich source of linoleic acid (LA; 74%), on proliferation and differentiation of neural stem cells (NSCs) in vitro. In this study, the effect of SSO on hypothalamic neurogenesis was investigated in vivo, in comparison to synthetic LA. Adult mice were treated with SSO (400 mg/kg) and pure synthetic LA (300 mg/kg), at similar concentrations of LA, for 8 weeks and then hypothalamic NSCs were cultured and subsequently used for Neurosphere-forming assay. In addition, serum levels of brain-derived neurotrophic factor (BNDF) were measured using enzyme-linked immunosorbent assay. Administration of SSO for 8 weeks in adult mice promoted the proliferation of NSCs isolated from SSO-treated mice.Immunofluorescence staining of the hypothalamus showed that the frequency of astrocytes (glial fibrillary acidic protein+ cells) are not affected by LA or SSO. However, the frequency of immature (doublecortin+ cells) and mature (neuronal nuclei+ cells) neurons significantly increased in LA- and SSO-treated mice, compared to vehicle. Furthermore, both LA and SSO caused a significant increase in the serum levels of BDNF. Importantly, SSO acted more potently than LA in all experiments.The presence of other fatty acids in SSO, such as oleic acid and palmitic acid, suggests that they could be responsible for SSO positive effect on hypothalamic proliferation and neurogenesis, compared to synthetic LA at similar concentrations.

Use of Social Media to View and Post Dentistry-related Information in Bahrain: A Cross-Sectional Study / 대한의료정보학회지

Objectives@#Healthcare-related information sharing via social media is on the rise following the coronavirus disease 2019 (COVID-19) pandemic. Dental practices primarily use social media to search, share, and communicate health-related information. Considering the increasing trend of using social media, the primary aim of the present study was to identify the use of social media by dentists and laypeople to post and view dentistry-related content in Bahrain. @*Methods@#This questionnaire-based cross-sectional study included adult participants and dentists. A pretested validated questionnaire was administered. The chi-square test for association was used to assess the association between categorical outcomes. A p-value of ≤ 0.05 was considered statistically significant. @*Results@#In total, 249 adult participants and 53 dentists were included. A substantial majority (83.5%) of the participants reported that they always used social media to view dentistry-related content, and 69.8% of the dentists felt that patients who use social media have better oral health awareness. A longer duration of social media usage showed significant associations with particularly viewing dentistry-related content (p = 0.008) and contacting dentists directly through social media for consultation (p = 0.055). @*Conclusions@#An extremely high percentage of the younger population in Bahrain is using various social media to discuss dentistry. This engagement should be wisely managed to promote dentistry-related information sharing, which can lead to increased awareness related to overall dental health. There is a definite need to enforce certain standard operating procedures in every country that will prevent the misuse of this technological advancement.

Diagnostic Value of D-Dimer and INR in Patients Suspected to Have Prosthetic Valve Dysfunction

ABSTRACT Introduction: Prosthetic valve dysfunction is a potentially critical complication of heart valve replacement. An easy and quickly applicable diagnostic procedure is required for recognizing the prosthetic valve dysfunction. The purpose of this study was to prospectively define the diagnostic value of D-dimer and INR level in predicting prosthetic valve dysfunction. Methods: This cross-sectional study was performed in 70 patients suspected to have prosthetic valve dysfunction admitted to Imam Ali Hospital, affiliated with Kermanshah University of Medical Sciences (KUMS), Kermanshah Province, Iran. Cinefluoroscopy, as the gold standard diagnostic test, was used for the diagnosis of prosthetic valve dysfunction in enrolled patients. Two milliliters of blood from each patient were taken into a tube containing sodium citrate anticoagulant. To evaluate D-dimer, the cutoff value was set at 500 ng/ml. Also, to evaluate international normalized ratio (INR), the cutoff value was set at 2. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of the serum markers were used to describe predictive properties. Results: Of 70 patients, 27 (38.6%) were male and 43 (61.4%) were female, and the mean age was 54.67±15.11 years (range, 18 to 80 years). Of 70 patients, 27 (38.6%) had prosthetic heart valve malfunction demonstrable by fluoroscopy, and 19 patients (27.1%) had D-dimer levels >500 ng/ml. Elevated D-dimer levels (>500 ng/ml) have been indicated to have sensitivity of 70.4%, and hence an NPV of 84.3%, specificity of 100%, PPV of 100%, NLR of 0.3, and the infinity value of PLR for predicting prosthetic valve dysfunction. There was a significant relationship between fluoroscopy and D-dimer test (P=0.001). A kappa coefficient value of 0.745 indicated a substantial agreement between D-dimer and fluoroscopy testing. Mixing test (combination of D-dimer and INR) showed to have 100% sensitivity, and hence a NPV of 69.8%, specificity of 69.8%, PPV of 51.8%, NLR of 1.41, and PLR of 1.44 for predicting prosthetic valve dysfunction. Conclusion: D-dimer with moderate sensitivity and high specificity is an ideal marker for the diagnosis of prosthetic valve dysfunction in suspected patients. Enhanced plasma D-dimer level is not by itself diagnostic of a prosthetic valve dysfunction but may alert physicians to refer the patient for more detailed examination, preferably by fluoroscopy. Mixing test with 100% sensitivity can apply as a rule-out test.

Correction methods for noncontact intraocular pressure measurement in patients with keratoconus and healthy individuals / Métodos de correção para medição sem contato da pressão intraocular em indivíduos normais e com ceratocone

ABSTRACT Purpose: The objective of this study was to investigate the usefulness of four different algorithms to correct noncontact intraocular pressure measurement errors in keratoconus patients and normal individuals. Methods: Noncorrected intraocular pressure and corrected intraocular pressures were measured in one eye of 34 patients with keratoconus and 34 age- and gender-matched healthy controls using Corvis Scheimpflug Technology. The correlation of noncorrected intraocular pressure and corrected intraocular pressures with age, axial length, corneal shape, thickness, and biomechanics was calculated. Corrected intraocular pressures were compared with noncorrected intraocular pressure using paired t test and Bland-Altman plots (95% limits of agreement). Results: The noncorrected intraocular pressure correlated with corneal thickness and biomechanical parameters in both groups (all p≤0.047), and front and back mean keratometry in the keratoconus group (r=-0.39, p=0.02, and r=0.39, p=0.02, respectively). After adjustment with different intraocular pressure correction algorithms, biomechanically corrected intraocular pressure showed a minimal correlation with corneal features and a nonsignificant difference with noncorrected intraocular pressure in the healthy group (-0.1 ± 1.1 mmHg, p=0.58; 95% limits of agreement: -2.3 to 2.1 mmHg). Conclusions: Measuring intraocular pressure using noncontact tonometry and its corrected forms with a corneal thickness-based simple linear formula in patients with keratoconus is associated with many errors. Using more complex formulas that take into consideration more corneal stiffness parameters in addition to corneal thickness, such as biomechanically corrected intraocular pressure formula, may be more reliable and beneficial in this group of patients.

RESUMO Objetivo: Investigar a utilidade de quatro algoritmos diferentes para corrigir erros de medição sem contato da pressão intraocular em pacientes saudáveis e com ceratocone. Métodos: A pressão intraocular não corrigida e as pressões intraoculares corrigidas foram medidas em um olho de 34 pacientes com ceratocone e 34 pacientes do grupo controle saudável pareados por idade e gênero usando a tecnologia Corvis Scheimpflug. Foi calculada a correlação da pressão intraocular não corrigida e das pressões intraoculares corrigidas com idade, comprimento axial e formato, espessura e biomecânica da córnea. As pressões intraoculares corrigidas foram comparadas com a pressão intraocular não corrigida usando o teste t pareado, e gráficos de Bland-Altman (limites de concordância de 95%). Resultados: A pressão intraocular não corrigida correlacionou-se com a espessura da córnea e com os parâmetros biomecânicos em ambos os grupos (todos p≤0,047) e a ceratometria média frontal e posterior no grupo com ceratocone (r=-0,39, p=0,02, r=0,39, p=0,02, respectivamente). Após o ajuste com diferentes algoritmos de correção da pressão intraocular, a pressão intraocular corrigida biomecanicamente revelou uma correlação mínima com as características da córnea e uma diferença não significativa com a pressão intraocular não corrigida no grupo saudável (-0,1 ± 1,1 mmHg, p=0,58; limites de concordância de 95%: -2,3 a 2,1 mmHg). Conclusões: A medição da pressão intraocular usando tonometria sem contato e suas formas corrigidas usando fórmulas lineares, simples, baseadas na espessura da córnea em pacientes com ceratocone estão associadas a muitos erros. O uso de fórmulas mais complexas que consideram mais parâmetros de rigidez da córnea além da espessura da córnea, como fórmula de pressão intraocular corrigida biomecanicamente, pode ser mais confiável e benéfico neste grupo de pacientes.

Can concomitant bladder neck incision and primary valve ablation reduce early re-admission rate and secondary intervention?

ABSTRACT Objective: To assess the effect of bladder neck morphology and its incision (BNI) in patients with posterior urethral valve (PUV) on early reintervention rate. Patients and methods: Infants undergoing PUV ablation (PVA) before 24 months of age and had at least 18 months of follow-up, were categorized into three groups according to the bladder neck appearance on baseline radiological and endoscopic examination: group 1; normal bladder neck underwent PVA, group 2; high bladder neck underwent PVA plus BNI, group 3; high bladder neck underwent PVA only. Early reintervention was defined as the need for check cystoscopy because of persistent renal function deterioration, worsening hydronephrosis and/or unsatisfactory VCUG improvement during the 1st six months post primary PVA. Results: Between 2000 and 2017, a total of 114 patients underwent PVA and met the study criteria with a median follow-up of 58 (18-230) months. For group 1, 16 (22.9%) patients needed readmission. Check cystoscopy was free and no further intervention was performed in 5(7.5%) and re-ablation was performed in 11(15.7%) patients. For group 2, 3(14.3%) patients needed reintervention. Re-ablation and re-ablation plus BNI were performed in 1(4.8%) and 2(9.5%), respectively. For group 3, cystoscopy was free in 1(4.3%), re-ablation and re-ablation plus BNI were performed 2(8.7%) and 1(4.3%), respectively. There were no significant differences in the re-admission and re-intervention rates among the three study groups (p=0.65 and p=0.50, respectively). Conclusion: In morphologically high bladder neck associated PUV, concomitant BNI with PVA doesn't reduce early re-intervention rate.

Vitamin E suppresses aortic ultrastructural alterations induced by toxic doses of monosodium glutamate / La vitamina E suprime las alteraciones ultraestructurales aórticas inducidas por dosis tóxicas de glutamato monosódico

SUMMARY: An association between certain food additives and chronic diseases is reported. Current study determined whether administering toxic doses of the food additive monosodium glutamate (MSG) into rats can induce aortopathy in association with the oxidative stress and inflammatory biomarkers upregulation and whether the effects of MSG overdose can be inhibited by vitamin E. MSG at a dose of (4 mg/kg; orally) that exceeds the average human daily consumption by 1000x was administered daily for 7 days to the rats in the model group. Whereas, rats treated with vitamin E were divided into two groups and given daily doses of MSG plus 100 mg/ kg vitamin E or MSG plus 300 mg/kg vitamin E. On the eighth day, all rats were culled. Using light and electron microscopy examinations, a profound aortic injury in the model group was observed demonstrated by damaged endothelial layer, degenerated smooth muscle cells (SMC) with vacuoles and condensed nuclei, vacuolated cytoplasm, disrupted plasma membrane, interrupted internal elastic lamina, clumped chromatin, and damaged actin and myosin filaments. Vitamin E significantly protected aorta tissue and cells as well as inhibited MSG-induced tissue malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The highest used vitamin E dosage was more effective. Additionally, a significant correlation was observed between the aortic injury degree and tissue MDA, TNF-α, IL-6, and superoxide dismutase (SOD) levels (p=0.001). Vitamin E effectively protects against aortopathy induced by toxic doses of MSG in rats and inhibits oxidative stress and inflammation.

RESUMEN: Se reporta una asociación entre ciertos aditivos alimentarios y enfermedades crónicas. El objetivo de este estudio fue determinar si la administración de dosis tóxicas del aditivo alimentario glutamato monosódico (MSG) en ratas puede inducir aortopatía en asociación con el estrés oxidativo y la regulación positiva de los biomarcadores inflamatorios y si el efecto de una sobredosis de MSG se puede inhibir con vitamina E. Se administró MSG diariamente durante 7 días una dosis de (4 g/kg; por vía oral) que excede el consumo diario humano promedio, en 1000x a las ratas del grupo modelo. Mientras que las ratas tratadas con vitamina E se dividieron en dos grupos y se administraron dosis diarias de MSG más 100 mg/kg de vitamina E o MSG más 300 mg/kg de vitamina E. Todas las ratas fueron sacrificadas en el octavo día. Usando exámenes de microscopía óptica y electrónica, se observó una lesión aórtica profunda en el grupo modelo demostrada por una capa endotelial dañada, células musculares lisas degeneradas (SMC) con vacuolas y núcleos condensados, citoplasma vacuolado, membrana plasmática rota, lámina elástica interna interrumpida, cromatina agrupada y filamentos de actina y miosina dañados. La vitamina E protegió significativamente el tejido y las células de la aorta, además de inhibir el malondialdehído tisular (MDA) inducido por MSG, la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-α). La dosis más alta de vitamina E utilizada fue más efectiva. Además, se observó una correlación significativa entre el grado de lesión aórtica y los niveles tisulares de MDA, TNF-α, IL-6 y superóxido dismutasa (SOD) (p=0,001). La vitamina E efectivamente protege contra la aortopatía inducida por dosis tóxicas de MSG en ratas e inhibe el estrés oxidativo y la inflamación.

Metformin and resveratrol suppress type 2 diabetes mellitus-induced articular cartilage damage in rats associated with the inhibition of inflammation and augmentation of proteoglycans / La metformina y el resveratrol suprimen el daño del cartílago articular inducido por la diabetes mellitus tipo 2 en ratas asociado con la inhibición de la inflamación y el aumento de proteoglicanos

SUMMARY: Induction of osteoarthritis (OA) following diabetes is characterized by a sever inflammation of the joints that can lead to disability. The cartilage content of proteoglycans can substantially be reduced, following the induction of diabetes mellitus associated with inflammation as well as knee joint injury, and the antidiabetic drug metformin combined with the anti-inflammatory agent resveratrol can prevent these deleterious effects. Therefore, insulin-independent diabetes, type 2 diabetes mellitus (T2DM) was induced in Albino rats by streptozotocin (STZ) injection (50 mg/kg) after being fed on a high carbohydrate and fat diets for 2 weeks. The protective group of rats which also received a single injection of STZ was treated daily with metformin (Met; 200 mg/kg) and resveratrol (Res; 30 mg/kg) for 12 weeks. Harvested knee joint tissues were prepared for basic histology stain and for proteoglycans staining using light microscopy. Histology images showed in diabetic rats (T2DM) OA development as demonstrated by profound injury to the knee joint and severe decrease of articular cartilage proteoglycans content, which were substantialy protected by Met+Res. Met+Res also significantly (p< 0.0001) decreased diabetes induced glycemia, dyslipidemia, and the inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP). In addition, there was a significant correlation between OA and glycemia, dyslipidemia, and inflammation. Collectively, we demonstrate an association between knee joint damage and biomarkers of glycemia, dyslipidemia, and inflammation in diabetes-induced OA, with metformin plus resveratrol providing protective effects.

RESUMEN: La inducción de osteoartritis (OA) después de la diabetes se caracteriza por una inflamación severa de las articulaciones que puede conducir a la discapacidad. El contenido de cartílago de proteoglicanos se puede reducir sustancialmente, luego de la inducción de diabetes mellitus asociada con inflamación y lesión en la articulación de la rodilla sin embargo, el fármaco antidiabético metformina combinado con el agente antiinflamatorio resveratrol puede prevenir estos efectos nocivos. Por lo tanto, se indujo diabetes insulino dependiente, diabetes mellitus tipo 2 (T2DM) en ratas albinas mediante inyección de estreptozotocina (STZ) (50 mg/kg) después de haber sido alimentadas con dietas ricas en carbohidratos y grasas durante 2 semanas. El grupo protector de ratas que también recibió una inyección única de STZ fue tratado diariamente con metformina (Met; 200 mg/kg) y resveratrol (Res; 30 mg/kg) durante 12 semanas. Tejidos de la articulación de la rodilla fueon retirados y teñidos con histología básica y tinción de proteoglicanos usando microscopía óptica. Las imágenes histológicas en ratas diabéticas mostraban (T2DM) desarrollo de OA visualizadas por una lesión profunda en la articulación de la rodilla y una disminución severa del contenido de proteoglicanos del cartílago articular, los cuales estaban sustancialmente protegidos por Met+Res. Met+Res. También disminuyó significativamente (p< 0,0001) la glucemia inducida por la diabetes, la dislipidemia y los biomarcadores inflamatorios, el factor de necrosis tumoral alfa (TNF-α), la interleucina-6 (IL-6) y la proteína C reactiva de alta sensibilidad (PCR-hs). Además, hubo una correlación significativa entre la OA y la glucemia, la dislipidemia y la inflamación. En conjunto, demostramos una asociación entre el daño de la articulación de la rodilla y los biomarcadores de glucemia, dislipidemia e inflamación en la OA inducida por diabetes, con metformina más resveratrol que brindan efectos protectores.

Student perceptions of an online surgical teaching programme during the COVID-19 pandemic at the University of KwaZulu-Natal: A short report

Background. The COVID-19 pandemic has led to an unprecedented global health crisis, with impacts on many facets of the health system, including lack of access to regular training wards and the need for social distancing, which posed particular challenges to undergraduate teaching. Objectives. To explore the perceptions of students of the online surgical programme at the University of KwaZulu-Natal (UKZN). Methods. An online survey was administered to 258 final-year students. Data were collected on student demographics, the impact of COVID-19 restrictions on the teaching programme, engagement and learning from live Zoom sessions, overall perceptions about the module and general feedback on students' experience of the programme. Results. Most students (84%, 77/91) supported the need to change to the virtual programme. The module was perceived as well-structured (89%, 81/91). Most students (87%, 79/91) regarded the online resource materials as beneficial. Analysis of open-ended responses showed that asynchronous delivery allowed students to review and revisit resources in their own time. Student challenges included poor internet connectivity, difficulty in concentrating where live sessions exceeded an hour, and lack of clinical exposure. Conclusion. Online teaching in medical education is a feasible option for remote learning. However, it cannot replace the benefits gained during clinical exposure. Findings from this study will help to set a benchmark for online surgical training at UKZN and develop best practices for blended teaching models. As we adapt to a new normal in the era of COVID-19, the disruptions and results of innovative teaching methods have the potential to change the future of medical education

The corona chronicles: Framing analysis of online news headlines of the COVID-19 pandemic in Italy, USA and South Africa

Background: The global coronavirus disease 2019 (COVID-19) pandemic, now in its second year, has resulted in a large corpus of literature in a number of disciplines, particularly virology and epidemiology. In contrast, scholarly inquiry in other areas of the health sciences, particularly in media representations and public health communication, is still emerging. Aim: As an integral stakeholder in communication during a pandemic, this descriptive study sought to delineate the media frames of the COVID-19 pandemic in online news headlines in the first month that the COVID-19 was declared a pandemic. Setting: Online news headlines in three global hotspots, namely Italy, the USA and South Africa, during the month of March 2020, were analysed. Methods: Thematic content analysis and epidemic framing typology. Results: The findings indicate that COVID-19 has been internationally portrayed as a lethal pandemic that destroys and disrupts human life. Discursive frames of consequences monopolised its coverage, whilst discursive frames of reassurance were rare, despite the high survival rate. One of the unique findings of this study is that the COVID-19 pandemic coverage included the naming of positive patients, who were thereby made known to the public. Conclusion: Internationally, COVID-19 pandemic coverage used consequence frames that dramatized loss of life instead of deploying frames of reassurance that foreground the high survival rate of this disease. Contribution: Results of the study may help inform public health communication of the COVID-19 pandemic, by offering a detailed description of the frames that journalists use in news headlines, all of which possibly influence public perception of the pandemic. Theoretically, the article has also contributed to the application of epidemic framing typology and has contributed to knowledge in the field of public health communication and the COVID-19 pandemic.

Canagliflozin reduces the contractile response of isolated heart of normal adult rats / Canagliflozin reduce la respuesta contráctil del corazón aislado de ratas adultas normales

SUMMARY: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a unique class of glucose-declining renal-targeted drugs. The SGLT2i Canagliflozin (CANA) is an anti-hyperglycemic drug that reduces various cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. This study aimed to explore the potential effects of CANA on the isolated healthy adult rat hearts to show if CANA has positive inotropic or cardiac depressant effects via analyzing the amplitude and frequency of cardiac contractions. In isolated normal adult rat hearts, the effects of CANA on cardiac contractility were examined. In a dose-response curve, CANA led to a significant cardiac depressant effect in a dose-dependent manner. This cardiac depressant effect of CANA (10-6 M) was not prevented by atropine. However, this cardiac depressant effect was partially antagonized by both Isoproterenol (10-5 M) and Calcium chloride (10-6 M), suggesting beta-adrenoceptor and calcium channel blocking actions. In addition, the cardiac depressant effect of CANA (10-6 M) was mitigated in part by Nitric oxide synthase inhibitor, L-NAME, suggesting that its action probably depends to some extent on the accumulation of nitric oxide, which decreases the rise of intracellular Calcium. Data from this study demonstrate that CANA has a significant cardiac relaxant effect in isolated hearts of healthy adult rats by different possible mechanisms. This inhibitory effect on cardiac contractility may help improve the diastolic ventricular filling providing a therapeutic potential to help the other cardioprotective mechanisms of CANA in the prevention and treatment of heart failure.

RESUMEN: Los inhibidores del cotransportador de sodio- glucosa 2 (SGLT2i) representan una clase única de fármacos dirigidos a los riñones que disminuyen la glucosa. El SGLT2i Canagliflozin (CANA) es un fármaco antihiperglucémico que reduce varios resultados cardiovasculares y renales en pacientes con diabetes mellitus tipo 2. Este estudio tuvo como objetivo explorar los efectos potenciales de CANA en corazones aislados de ratas adultas sanas para indicar si CANA tiene efectos inotrópicos o depresores cardíacos positivos mediante el análisis de la amplitud y la frecuencia de las contracciones cardíacas. En corazones aislados de ratas adultas normales, se examinaron los efectos de CANA sobre la contractilidad cardíaca. En una curva de dosis-respuesta, CANA condujo a un efecto depresor cardíaco significativo de manera dependiente de la dosis. Este efecto depresor cardíaco de CANA (10-6 M) no fue impedido por la atropina. Sin embargo, este efecto depresor cardíaco fue parcialmente antagonizado tanto por el isoproterenol (10-5 M) como por el cloruro de calcio (10-6 M), lo que sugiere acciones bloqueadoras de los receptores beta adrenérgicos y de los canales de calcio. Además, el efecto depresor cardíaco de CANA (10-6 M) fue mitigado en parte por el inhibidor de la sintasa de óxido nítrico, L-NAME, lo que sugiere que su acción probablemente depende en cierta medida de la acumulación de óxido nítrico, lo que disminuye el aumento de calcio intracelular. Los datos de este estudio demuestran que CANA tiene un efecto relajante cardíaco significativo en corazones aislados de ratas adultas sanas por diferentes mecanismos posibles. Este efecto inhibitorio sobre la contractilidad cardíaca puede ayudar a mejorar el llenado ventricular diastólico proporcionando un potencial terapéutico para ayudar a los otros mecanismos cardioprotectores de CANA en la prevención y tratamiento de la insuficiencia cardíaca.

Paracetamol poisoning induces acute liver injury in rats: inhibition of miR-155/cd45 axis-mediated antioxidant depletion and hepatotoxicity using quercetin and resveratrol / La intoxicación por paracetamol induce daño hepático agudo en ratas: inhibición de la depleción de antioxidantes mediado por el eje miR-155/cd45 y hepatotoxicidad usando quercetina y resveratrol

SUMMARY: Ingestion of an overdose of paracetamol (also called acetaminophen, or APAP) induces hepatotoxicity that can lead to liver failure. The link between the pro-inflammatory microRNA-155 (miR-155) and leukocyte infiltration (CD45) in APAP- antioxidant depletion and liver toxicity with and without the natural polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) has not been previously studied. Therefore, acute hepatic injury was induced in rats by 2 g/kg APAP (single dose, orally) and another group started QUR (50 mg/kg) plus RES (30 mg/kg) treatment one week prior to APAP ingestion. Animals were culled 24 hours post the paracetamol treatment. APAP overdose induced hepatic and blood levels of miR-155 expression, CD45 (leukocyte common antigen) immunostaining, degenerated hepatocytes, and hepatic injury enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were markedly decreased by QUR+RES. Whereas, APAP intoxication ameliorated liver tissue levels of the antioxidants, glutathione peroxidase and superoxide dismutase that were augmented by QUR+RES. Moreover, a significant (p<0.05) correlation between miR-155/CD45 axis and liver tissue injury was observed. These findings show that paracetamol intoxication augments miR- 155/CD45 axis-mediated modulation of antioxidants and liver injury in rats, and is protected by QUR+RES.

RESUMEN: La ingestión de una sobredosis de paracetamol (también llamado acetaminofeno o APAP) induce hepatotoxicidad que puede provocar insuficiencia hepática. El vínculo entre el microARN-155 proinflamatorio (miR-155) y la infiltración de leucocitos (CD45) en el agotamiento de APAP- antioxidante y la toxicidad hepática con y sin los compuestos polifenólicos naturales, quercetina (QUR) más resveratrol (RES) no ha sido previamente investigado. En este estudio, se indujo daño hepático agudo en ratas con 2 g/kg de APAP (dosis única, por vía oral) y otro grupo comenzó el tratamiento con QUR (50 mg/ kg) más RES (30 mg/kg) una semana antes de la ingestión de APAP. Los animales se sacrificaron 24 horas después del tratamiento con paracetamol. La sobredosis de APAP indujo niveles hepáticos y sanguíneos de expresión de miR-155, inmunotinción de CD45 (antígeno leucocitario común), degeneración de los hepatocitos y daño hepático enzimático; alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST), disminuyeron notablemente con QUR+RES. Mientras que la intoxicación con APAP mejoró los niveles de antioxidantes, glutatión peroxidasa y superóxido dismutasa en el tejido hepático los que aumentaron con QUR+RES. Además, se observó una correlación significativa (p<0,05) entre el eje miR-155/CD45 y la lesión del tejido hepático. Estos hallazgos muestran que la intoxicación por paracetamol aumenta la modulación mediada por el eje miR-155/CD45 de los antioxidantes y la lesión hepática en ratas, y está protegida por QUR+RES.