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1.
Medicine (Baltimore) ; 100(17): e22387, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907086

RESUMO

INTRODUCTION: Drug induced oral erythema multiforme a rare clinical entity which involves only the lips and oral mucosa without skin involvement. These lesions are difficult in diagnosing with other oral ulcerative lesions with similar clinical manifestations. PATIENT CONCERNS: This article presents 2 case reports of Oral erythema multiforme in which drugs were the precipitating factor. Its etiopathogenesis, differential diagnosis and treatment modalities of the disease is discussed. DIAGNOSIS: Based on patient's complaints, drug history and clinical appearance, provisional diagnosis of drug induced erythema multiforme was considered. INTERVENTION: For case 1, patient was instructed to discontinue usage of drug and prescribed systemic steroid (Prednisolone 10 mg/d) for a week along with germicidal drugs to prevent secondary infection. Medication was tapered to 5 mg/d after first week.For case 2, patient was instructed to discontinue the drug and systemic steroid prednisolone 20 mg /d for 1 week with tapering dose of 10 mg/d for the second week was administered. OUTCOME: For case 1 and case 2 healing of the lesions were evident on third week of follow up. CONCLUSION: Medications should be taken under medical supervision. Over the counter drugs might lead to allergic reactions like drug induced oral erythema multiforme, which is a rare variant and needs to be differentiate from other oral ulcerative lesion for prompt management and follow-up.


Assuntos
Acetaminofen/efeitos adversos , Diclofenaco/efeitos adversos , Eritema Multiforme/induzido quimicamente , Úlceras Orais/induzido quimicamente , Adolescente , Adulto , Diagnóstico Diferencial , Eritema Multiforme/diagnóstico , Humanos , Lábio/patologia , Masculino , Mucosa Bucal/patologia , Úlceras Orais/diagnóstico
2.
Molecules ; 26(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804228

RESUMO

Sophora flavescens, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC's activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sophora/química , terc-Butil Hidroperóxido/efeitos adversos , Alanina Transaminase/metabolismo , Animais , Antioxidantes/fisiologia , Aspartato Aminotransferases/metabolismo , Linhagem Celular Tumoral , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Células Hep G2 , Medicina Herbária/métodos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807047

RESUMO

Acetaminophen (APAP) is one of the most commonly used analgesic and anti-pyretic drugs, and APAP intoxication is one of the main reasons for liver transplantation following liver failure in the Western world. While APAP poisoning ultimately leads to liver necrosis, various programmed cell death modalities have been implicated, including ER stress-triggered apoptosis. The BCL-2 family member BOK (BCL-2-related ovarian killer) has been described to modulate the unfolded protein response and to promote chemical-induced liver injury. We therefore investigated the impact of the loss of BOK following APAP overdosing in mice. Surprisingly, we observed sex-dependent differences in the activation of the unfolded protein response (UPR) in both wildtype (WT) and Bok-/- mice, with increased activation of JNK in females compared with males. Loss of BOK led to a decrease in JNK activation and a reduced percentage of centrilobular necrosis in both sexes after APAP treatment; however, this protection was more pronounced in Bok-/- females. Nevertheless, serum ALT and AST levels of Bok-/- and WT mice were comparable, indicating that there was no major difference in the overall outcome of liver injury. We conclude that after APAP overdosing, loss of BOK affects initiating signaling steps linked to ER stress, but has a more minor impact on the outcome of liver necrosis. Furthermore, we observed sex-dependent differences that might be worthwhile to investigate.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Overdose de Drogas/complicações , Predisposição Genética para Doença , Proteínas Proto-Oncogênicas c-bcl-2/deficiência , Acetaminofen/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Feminino , Regulação da Expressão Gênica , Genes p53 , Masculino , Camundongos , Camundongos Knockout , Índice de Gravidade de Doença , Fatores Sexuais , Resposta a Proteínas não Dobradas/efeitos dos fármacos
4.
Int J Mol Sci ; 22(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800244

RESUMO

Hypoxia-induced mitogenic factor (HIMF), which is also known as resistin-like molecule α (RELM-α), found in inflammatory zone 1 (FIZZ1), or resistin-like alpha (retlna), is a cysteine-rich secretory protein and cytokine. HIMF has been investigated in the lung as a mediator of pulmonary fibrosis, inflammation and as a marker for alternatively activated macrophages. Although these macrophages have been found to have a role in acute liver injury and acetaminophen toxicity, few studies have investigated the role of HIMF in acute or immune-mediated liver injury. The aim of this focused review is to analyze the literature and examine the effects of HIMF and its human homolog in organ-specific inflammation in the lung and liver. We followed the guidelines set by PRISMA in constructing this review. The relevant checklist items from PRISMA were included. Items related to meta-analysis were excluded because there were no randomized controlled clinical trials. We found that HIMF was increased in most models of acute liver injury and reduced damage from acetaminophen-induced liver injury. We also found strong evidence for HIMF as a marker for alternatively activated macrophages. Our overall risk of bias assessment of all studies included revealed that 80% of manuscripts demonstrated some concerns in the randomization process. We also demonstrated some concerns (54.1%) and high risk (45.9%) of bias in the selection of the reported results. The need for randomization and reduction of bias in the reported results was similarly detected in the studies that focused on HIMF and the liver. In conclusion, we propose that HIMF could be utilized as a marker for M2 macrophages in immune-mediated liver injury. However, we also detected the need for randomized clinical trials and additional experimental and human prospective studies in order to fully comprehend the role of HIMF in acute or immune-mediated liver injury.


Assuntos
Lesão Renal Aguda/imunologia , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Fígado/imunologia , Pulmão/imunologia , Macrófagos/imunologia , Acetaminofen/efeitos adversos , Lesão Renal Aguda/patologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Pulmão/patologia , Macrófagos/patologia , Especificidade de Órgãos/imunologia
5.
Zhonghua Gan Zang Bing Za Zhi ; 29(3): 279-283, 2021 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-33902198

RESUMO

Acetaminophen (APAP) is a widely used antipyretic and analgesic drug that is safe and effective in the therapeutic doses, but overdose may cause hepatotoxicity and even acute liver failure (ALF). Finding reliable biomarkers for APAP toxicity is not only a hot spot of current research, but also a problem that needs to be solved urgently. Clinicians should consider the existence of APAP hepatotoxicity when using APAP treatment, and explain that APAP may have a certain degree of dose dependence. This paper reviews the most promising biomarkers currently being evaluated, and expounds their application in the field of APAP hepatotoxicity, as well as the mechanism of mitochondrial damage and mitochondrial autophagy, thereby contributing to the diagnosis, prognosis, mechanism and research progress of therapeutic targets of APAP hepatotoxicity.


Assuntos
Analgésicos não Entorpecentes , Doença Hepática Induzida por Substâncias e Drogas , Overdose de Drogas , Falência Hepática Aguda , Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/toxicidade , Humanos , Fígado
6.
Med J Aust ; 214(7): 324-331, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33786837

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of paracetamol as an analgesic medication in a range of painful conditions. STUDY DESIGN: Systematic review of systematic reviews of the analgesic effects of paracetamol in randomised, placebo-controlled trials. Conduct of systematic reviews was assessed with AMSTAR-2; confidence in effect estimates (quality of evidence) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. DATA SOURCES: MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews; systematic reviews published 1 January 2010 - 30 April 2020. DATA SYNTHESIS: We extracted pain and adverse events outcomes from 36 systematic reviews that assessed the efficacy of paracetamol in 44 painful conditions. Continuous pain outcomes were expressed as mean differences (MDs; standardised 0-10-point scale); dichotomous outcomes were expressed as risk ratios (RRs). There is high quality evidence that paracetamol provides modest pain relief for people with knee or hip osteoarthritis (MD, -0.3 points; 95% CI, -0.6 to -0.1 points) and after craniotomy (MD, -0.8 points; 95% CI, -1.4 to -0.2 points); there is moderate quality evidence for its efficacy in tension-type headache (pain-free at 2 hours: RR, 1.3; 95% CI, 1.1-1.4) and perineal pain soon after childbirth (patients experiencing 50% pain relief: RR, 2.4; 95% CI, 1.5-3.8). There is high quality evidence that paracetamol is not effective for relieving acute low back pain (MD, 0.2 points; 95% CI, -0.1 to 0.4 points). Evidence regarding efficacy in other conditions was of low or very low quality. Frequency of adverse events was generally similar for people receiving placebo or paracetamol, except that transient elevation of blood liver enzyme levels was more frequent during repeated administration of paracetamol to patients with spinal pain (RR, 3.8; 95% CI, 1.9-7.4). CONCLUSIONS: For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain. Investigations that evaluate more typical dosing regimens are required. PROSPERO REGISTRATION: CRD42015029282 (prospective).


Assuntos
Acetaminofen/uso terapêutico , Manejo da Dor/métodos , Dor/tratamento farmacológico , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos não Entorpecentes/uso terapêutico , Estudos de Casos e Controles , Craniotomia , Gerenciamento de Dados , Humanos , Dor Lombar/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Placebos/administração & dosagem , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Cefaleia do Tipo Tensional/tratamento farmacológico , Resultado do Tratamento
7.
Sci Rep ; 11(1): 5087, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658615

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used in patients with respiratory infection, but their safety in coronavirus disease 19 (Covid-19) patients has not been fully investigated. We evaluated an association between NSAID use and outcomes of Covid-19. This study was a retrospective observational cohort study based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea by May 15, 2020. These claims comprised all Covid-19-tested cases and history of medical service use for the past 3 years in these patients. The primary outcome was all-cause mortality, and the secondary outcome was need for ventilator care. Among 7590 patients diagnosed with Covid-19, two distinct cohorts were generated based on NSAID or acetaminophen prescription within 2 weeks before Covid-19 diagnosis. A total of 398 patients was prescribed NSAIDs, and 2365 patients were prescribed acetaminophen. After propensity score matching, 397 pairs of data set were generated, and all-cause mortality of the NSAIDs group showed no significant difference compared with the acetaminophen group (4.0% vs. 3.0%; hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.63-2.88; P = 0.46). The rate of ventilator care also did not show significantly different results between the two groups (2.0% vs. 1.3%; HR, 1.60; 95% CI 0.53-5.30; P = 0.42). Use of NSAIDs was not associated with mortality or ventilator care in Covid-19 patients. NSAIDs may be safely used to relieve symptoms in patients with suspicion of Covid-19.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , /mortalidade , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Administração Oral , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pontuação de Propensão , República da Coreia/epidemiologia , Estudos Retrospectivos , /patogenicidade
8.
Zhonghua Gan Zang Bing Za Zhi ; 29(1): 67-71, 2021 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-33541026

RESUMO

Objective: To investigate the protective effect of Colgalt2 gene deletion on acute liver injury induced by acetaminophen (APAP) in mice. Methods: Colgalt2(+/+) wild-type control mice and Colgalt2(-/-) mice (all C57BL/6J strains) were selected as the research subject. APAP solution was injected intraperitoneally to establish a mouse model of acute liver injury. The mouse were divided into four groups: Colgalt2(+/+) wild-type control group, Colgalt2(+/+) wild-type drug group (APAP 500 mg/kg), Colgalt2(-/-) control group, and Colgalt2(-/-) drug group (APAP 500 mg/kg). The survival rate was measured to plot survival curve. Liver function was evaluated by detecting serum ALT and AST levels. Liver histopathological changes were observed by HE staining to evaluate the condition of liver injury. Western blot was used to detect protein c-Jun N-terminal kinase (JNK)-related liver injury. Results: Compared with Colgalt2(+/+) mice, the survival rate was significantly increased after giving APAP to Colgalt2(-/-) mice (86.7% vs. 40%), and liver cell necrosis and inflammatory cell infiltrates of Colgalt2(+/+) mice were milder. Serum ALT, and AST level was significantly decreased [ALT: (5 291.9 ± 1 016.34) U/L vs. (1 616.9 ± 330.65) U/L, P = 0.000; AST: (4 978.0 ± 1 028.43) U/L vs. (1 851.0 ± 437.55) U/L, P = 0.000]. The expression level of JNK was significantly decreased in liver tissue. Conclusion: Colgalt2 gene deletion has a protective effect on acute liver injury induced by acetaminophen (APAP) in mice. Therefore, Colgalt2 may be a potential therapeutic option for acetaminophen-induced hepatotoxicity.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/efeitos adversos , Acetaminofen/metabolismo , Animais , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Deleção de Genes , Glicosiltransferases/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
9.
Phytomedicine ; 83: 153479, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33561764

RESUMO

BACKGROUND: The fruit of Terminalia chebula Retz. is one of the most widely used herbal drug in Traditional medicine prescriptions including those for liver diseases. In the screening of bioactive constituents that have potential hepatoprotective activity, chebulinic acid (CA) which is a major chemical constituent of T. chebula fruit showed potent activity. PURPOSE: This work was conducted to investigate the hepatoprotective activity and mechanisms of CA. METHODS: The hepatoprotective effect of CA was examined on hepatotoxic models of cells, zebrafish larvae and mice caused by tert-butyl hydrogen peroxide (t-BHP), acetaminophen (APAP) and CCl4, respectively. RESULTS: Pretreatment with CA could prevent t-BHP-induced damage in L-02 hepatocytes by blocking the production of ROS, reducing LDH levels and enhancing HO-1 and NQO1 expression via MAPK/Nrf2 signaling pathway. In animal experiments, CA significantly protected mice from CCl4-induced liver injury, as demonstrated by reduced ALT, AST and MDA levels, enhanced SOD activity, improved liver histopathological changes, and the activation of the Nrf2/HO-1 signaling pathway. CA metabolized to chebulic acid isomers with DPPH radical scavenging activity. In a transgenic zebrafish line with liver specific expression of DsRed RFP, CA diminished the hepatotoxicity induced by 10 mM APAP. CONCLUSION: Experiments in cell and two animal models demonstrated consistent results and comprehensively expounded the hepatoprotective effects of CA.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Taninos Hidrolisáveis/farmacologia , Substâncias Protetoras/farmacologia , Terminalia/química , Acetaminofen/efeitos adversos , Animais , Animais Geneticamente Modificados , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Frutas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Larva/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , terc-Butil Hidroperóxido/toxicidade
11.
Biomed Pharmacother ; 134: 111150, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33395599

RESUMO

Risk factors related to the development of acetaminophen (APAP)-induced adverse reactions and liver injury remain uncertain. Sleep disorders have been linked to some health outcomes. This study examined the associations of sleep disorders with APAP-induced adverse reactions or liver injury and the possible mechanisms. From NIS database, adverse reactions, liver injury and sleep disorders were identified. Factors associated with the risk of the total adverse effects or liver injury were examined with logistic regression. From Gene Expression Omnibus database, datasets GSE111828, containing transcriptome data based on RNA-seq analysis from liver samples extracted from mice post APAP administration, and GSE92913, containing transcriptome data based on microarray analysis from liver samples extracted from mice with sleep deprivation, were analyzed. A total of 4372754 patients without and 91314 patients with sleep disorders were eligible for analyses. Both before and after propensity score matching, APAP-induced adverse reactions were higher in patients with sleep disorders than in patients without. In multivariate regression, sleep disorders were associated with higher odds of APAP-induced adverse reactions (adjusted OR [aOR] 2.005, 95 % CI 1.343-2.995) and liver injury (aOR 2.788, 95 % CI 1.310-5.932). Genes that were enriched in bile secretion and retinol metabolism and PPAR signaling pathways were basically down-regulated in livers of mice after APAP administration and livers of mice with sleep deprivation. This study shows that sleep disorders may be novel independent risk factors for APAP-associated adverse reactions and liver injury and provides bioinformation linking sleep disorders to increased risk of APAP-induced liver injury.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Transtornos do Sono-Vigília/complicações , Adulto , Animais , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/genética , Estudos Transversais , Bases de Dados Genéticas , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Pacientes Internados , Masculino , Camundongos , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Transdução de Sinais , Sono , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/fisiopatologia , Transcriptoma
12.
Am J Public Health ; 111(3): 471-474, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33476235

RESUMO

Objectives. To present data for opioid misuse among US reservation-based American Indian (AI) adolescents and to compare these data with national rates from Monitoring the Future (MTF).Methods. Data were from a national sample of 33 schools participating in a substance use epidemiological survey of reservation-based AI adolescents during 2018 and 2019. Participants were 8th-, 10th-, and 12th-grade AI students (n = 1592). Measures included 12-month and 30-day use of OxyContin, Vicodin, heroin, and narcotics. We computed prevalence and compared it with MTF national prevalence.Results. Across grades, AI youths demonstrated significantly greater past 12-month and 30-day opioid use relative to a national sample. Significant absolute differences in 12-month and 30-day prevalence levels ranged from 1.6% (8th-grade heroin) to 4.7% (12th-grade narcotics) and from 1.6% (12th-grade narcotics) to 1.8% (12th-grade heroin), respectively.Conclusions. Opioid misuse prevalence levels were significantly greater for reservation-based AI adolescents relative to national prevalence levels.Public Health Implications. Findings suggest that implementation of evidence-based efforts, adapted or developed to be culturally appropriate, should be significantly increased in tribal communities, along with policies to address the unique social, economic, and health issues they face.


Assuntos
Acetaminofen/efeitos adversos , Comportamento do Adolescente , Hidrocodona/efeitos adversos , Índios Norte-Americanos/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Combinação de Medicamentos , Feminino , Humanos , Masculino , Assunção de Riscos , Instituições Acadêmicas/estatística & dados numéricos , Estados Unidos
13.
BMJ Case Rep ; 14(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419747

RESUMO

A 75-year-old woman was admitted to a regional hospital with an acute kidney injury (AKI) and nausea on a background of recent treatment for Staphylococcus aureus bacteraemia secondary to pneumonia. The treatment thereof resulted in a high anion gap metabolic acidosis (HAGMA). The pneumonia was initially treated with intravenous piperacillin and tazobactam and the patient transferred to a tertiary hospital. There, the diagnosis of S. aureus bacteraemia secondary to a pulmonary source was confirmed and treatment was changed to intravenous flucloxacillin and the patient was discharged to hospital in the home (HITH is a service that allows short-term healthcare at home to be provided to people who would otherwise need to be in hospital) to complete the antibiotic course. Five weeks after commencing flucloxacillin, the patient was referred back to hospital with nausea and worsening kidney function with an associated significant HAGMA. The patient has a background of chronic kidney disease and chronic back pain for which she was taking long-term paracetamol. The HAGMA was determined to be due to a pyroglutamic acidosis (PGA), deemed secondary to the combined use of paracetamol and flucloxacillin. This was subsequently confirmed with a plasma pyroglutamic acid concentration level of 7467 µmol/L (reference range 20-50 µmol/L) and a urinary level of 1700 mmol/mol creatinine (<110 mmol/mol creatinine). To our knowledge, this is the highest plasma and urinary levels published to date. Furthermore, considering the common use of paracetamol and penicillins, it is important to recognise HAGMA as a potential complication of co-administration of paracetamol and iso-oxylopenicillin. The HAGMA resolved after cessation of flucloxacillin despite the continuation of paracetamol and without administration of N-acetylcysteine. PGA-related HAGMA appears to be a unique potential side effect of iso-oxylopenicillin rather than other beta-lactams.


Assuntos
Acetaminofen/efeitos adversos , Acidose/induzido quimicamente , Antibacterianos/efeitos adversos , Antipiréticos/efeitos adversos , Floxacilina/efeitos adversos , Ácido Pirrolidonocarboxílico/metabolismo , Acidose/diagnóstico , Lesão Renal Aguda/complicações , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/terapia , Idoso , Bacteriemia/tratamento farmacológico , Feminino , Humanos , Infecções Estafilocócicas/tratamento farmacológico
14.
Trials ; 22(1): 105, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516238

RESUMO

BACKGROUND: To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA). METHODS: In this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded. RESULTS: Seventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups (p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen's d) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%). CONCLUSION: The results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2017/02/007962 . Registered on 27 February 2017.


Assuntos
Acetaminofen/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Acetaminofen/efeitos adversos , Adulto , Curcuma/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Extratos Vegetais/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
15.
Anaesth Intensive Care ; 48(5): 404-408, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33016081

RESUMO

Investigation of intraoperative anaphylaxis includes the exclusion of potential trigger agents the individual was exposed to within a plausible interval preceding the reaction. Occasionally, none of these agents will test positive. In this situation it is important to consider that excipients may be responsible for anaphylaxis, that the dilutions prepared to test the medication may not contain an appropriate concentration of the excipient to induce a positive skin reaction, or if an alternative formulation of the medication is tested, it may not contain the culprit excipient. This case describes a patient, who previously experienced an anaphylactic reaction to Betadine® (Sanofi-Aventis Australia Pty Ltd, North Ryde BC, NSW) experiencing anaphylaxis in the recovery period after general anaesthesia where Betadine was avoided. The recently administered therapeutics were excluded by skin testing, however further investigation determined that a povidone-containing formulation of paracetamol had been administered. Skin testing with povidone-containing paracetamol resulted in a positive reaction in the patient, but not in a volunteer control. Pharmaceutical excipients are added to medications to increase absorption, shelf-life and efficacy. Different brands of the same drug may contain different excipients. When testing for anaphylaxis with such compounds one must be sure the dilution is appropriate for both the parent compound and the excipient to ensure the accuracy of skin-prick and intradermal testing. This case demonstrates the potential for excipients to cause severe allergy and the importance of detailed history pertaining to previous allergic episodes as even the most unlikely of medications can potentially result in anaphylaxis due to excipients.


Assuntos
Acetaminofen , Analgésicos não Entorpecentes , Anafilaxia , Excipientes , Povidona , Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Anafilaxia/induzido quimicamente , Austrália , Excipientes/efeitos adversos , Humanos , Povidona/efeitos adversos , Testes Cutâneos
16.
Cochrane Database Syst Rev ; 8: CD007789, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32797734

RESUMO

BACKGROUND: Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended. There is concern about the use of oral opioids for acute pain leading to dependence. This is an update of a Cochrane Review published in 2015. OBJECTIVES: To assess the benefits or harms of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries. SEARCH METHODS: We searched the CENTRAL, 2020 Issue 1, MEDLINE (from 1946), and Embase (from 1980) to January 2020; other databases were searched to February 2019. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials involving people with acute soft tissue injury (sprain, strain, or contusion of a joint, ligament, tendon, or muscle occurring within 48 hours of inclusion in the study), and comparing oral NSAIDs versus paracetamol (acetaminophen), opioid, paracetamol plus opioid, or complementary and alternative medicine. The outcomes were pain, swelling, function, adverse effects, and early re-injury. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data, and assessed risk of bias. We assessed the quality of the evidence using GRADE methodology. MAIN RESULTS: We included 20 studies, with 3305 participants. Three studies included children only. The others included predominantly young adults; approximately 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, and five were at high risk of selective outcome reporting bias. Some evidence relating to pain relief was high certainty. Other evidence was either moderate, low or very low certainty, reflecting study limitations, indirectness, imprecision, or combinations of these. Thus, we are certain or moderately certain about some of the estimates, and uncertain or very uncertain of others. Eleven studies, involving 1853 participants compared NSAIDs with paracetamol. There were no differences between the two groups in pain at one to two hours (1178 participants, 6 studies; high-certainty evidence), at days one to three (1232 participants, 6 studies; high-certainty evidence), and at day seven or later (467 participants, 4 studies; low-certainty evidence). There was little difference between the groups in numbers of participants with minimal swelling at day seven or later (77 participants, 1 study; low-certainty evidence). Very low-certainty evidence from three studies (386 participants) means we are uncertain of the finding of little difference between the two groups in return to function at day seven or later. There was low-certainty evidence from 10 studies (1504 participants) that NSAIDs may slightly increase the risk of gastrointestinal adverse events compared with paracetamol. There was low-certainty evidence from nine studies (1679 participants) of little difference in neurological adverse events between the NSAID and paracetamol groups. Six studies, involving 1212 participants compared NSAIDs with opioids. There was moderate-certainty evidence of no difference between the groups in pain at one hour (1058 participants, 4 studies), and low-certainty evidence for no difference in pain at days four or seven (706 participants, 1 study). There was very low-certainty evidence of no important difference between the groups in swelling (84 participants, 1 study). Participants in the NSAIDs group were more likely to return to function in 7 to 10 days (542 participants, 2 studies; low-certainty evidence). There was moderate-certainty evidence (1143 participants, 5 studies) that NSAIDs were less likely to result in gastrointestinal or neurological adverse events compared with opioids. Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. Very low-certainty evidence means we are uncertain of the findings of no differences between the two interventions in the numbers with little or no pain at day one (51 participants, 1 study), day three (149 participants, 2 studies), or day seven (138 participants, 2 studies); swelling (230 participants, 3 studies); return to function at day seven (89 participants, 1 study); and the risk of gastrointestinal or neurological adverse events (141 participants, 3 studies). No studies reported re-injury rates. No studies compared NSAIDs with oral complementary and alternative medicines, AUTHORS' CONCLUSIONS: Compared with paracetamol, NSAIDs make no difference to pain at one to two hours and at two to three days, and may make no difference at day seven or beyond. NSAIDs may result in a small increase in gastrointestinal adverse events and may make no difference in neurological adverse events compared with paracetamol. Compared with opioids, NSAIDs probably make no difference to pain at one hour, and may make no difference at days four or seven. NSAIDs probably result in fewer gastrointestinal and neurological adverse effects compared with opioids. The very low-certainly evidence for all outcomes for the NSAIDs versus paracetamol with opioid combination analgesics means we are uncertain of the findings of no differences in pain or adverse effects. The current evidence should not be extrapolated to adults older than 65 years, as this group was not well represented in the studies.


Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Contusões/tratamento farmacológico , Lesões dos Tecidos Moles/tratamento farmacológico , Entorses e Distensões/tratamento farmacológico , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Doença Aguda , Administração Oral , Adulto , Analgésicos/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Viés , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tempo para o Tratamento , Adulto Jovem
17.
Zhonghua Er Ke Za Zhi ; 58(8): 682-683, 2020 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-32842391

RESUMO

A 4-month-old child with skin rash for 2 days and fever for 1 day was hospitalized in the Department of Pediatrics of Erdos Central Hospital in November 2019. According to the clinical symptoms, medical history and medication history at the time of admission, it was diagnosed as urticaria with angioneuroedema. In this case, the urticaria occurred 3 days after acetaminophen administration, which is a delayed reaction.


Assuntos
Acetaminofen/efeitos adversos , Angioedema/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Urticária/induzido quimicamente , Acetaminofen/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Febre , Humanos , Lactente
18.
Medicine (Baltimore) ; 99(34): e21816, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846821

RESUMO

BACKGROUND: Due to the soft tissue injury and large amount of bone destruction involved, undesirable postoperative pain remains a challenge for both patients and surgeons after unicompartmental knee replacement (UKR). However, there are no studies comparing the effectiveness of oral and intravenous acetaminophen as part of a standard multimodal perioperative pain regimen after UKR. Thus, this prospective randomized study was conducted to compare pain control outcomes with postoperative oral versus intravenous acetaminophen use in adults undergoing UKR. METHODS: The institutional review board of the Traditional Chinese Medicine- western Medicine Hospital of Cangzhou approved the study protocol. This blinded and randomized study was carried out in accordance with the principles of the Helsinki Declaration. We included patients who were scheduled for UKR with an American Society of Anesthesiologists status of I to III, who were mentally competent, and who were able to give consent for enrolment in the study. Patients were randomly assigned on a 1:1 basis to receive either intravenous acetaminophen or oral acetaminophen. We ensured that the patients, care providers, and outcome assessors were blinded to the group assignment during the study period. Primary outcomes were postoperative pain at rest and during motion (knee flexion of 45°) measured using a visual analog scale score. Secondary outcomes included morphine consumption at 24, 48, and 72 hours after surgery, length of hospital stay, range of motion, daily ambulation distance, and adverse events occurrence. All statistical analyses were performed using SPSS 25.0. Differences associated with a P value of <.05 were considered statistically significant. RESULTS: It was hypothesized that patients receiving intravenous acetaminophen would exhibit similar postoperative outcomes compared with patients receiving oral acetaminophen. TRIAL REGISTRATION: This study was registered in Research Registry (researchregistry5825).


Assuntos
Acetaminofen/administração & dosagem , Artroplastia do Joelho/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/efeitos adversos , Administração Intravenosa , Administração Oral , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Humanos , Articulação do Joelho/fisiopatologia , Tempo de Internação , Morfina/uso terapêutico , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Projetos de Pesquisa , Caminhada
19.
Yakugaku Zasshi ; 140(7): 943-947, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612060

RESUMO

Concomitant therapy with acetaminophen (APAP) and low-dose aspirin is often used in clinical settings; however, it is unclear whether this combination is involved in the progression of chronic kidney disease (CKD). We hypothesized that concomitant therapy with APAP and low-dose aspirin may cause CKD progression. We carried out a retrospective 6-year cohort study that included all patients who received low-dose aspirin from January 2011 to December 2016 at Kaetsu Hospital. Primary outcome was defined as CKD progression at the end of the study compared with baseline. Among the 441 patients treated during the study period, we identified 89 cases of CKD progression. Multivariate regression analysis showed that exposure to APAP>50 g [odds ratio (OR), 2.68, 95% confidence interval (CI), 1.08-6.70], age increase by 1 year (OR, 1.05, 95% CI, 1.02-1.08), and diabetes mellitus (OR, 2.40, 95% CI, 1.41-4.08) had positive associations with CKD progression. Our findings suggested that concomitant therapy with APAP and low-dose aspirin increased the risk of CKD progression. Therefore, we recommend more thorough monitoring of serum creatinine when patients are on such concomitant therapy. Moreover, it is important to advise users of low-dose aspirin to avoid unnecessary use of APAP, in order to reduce the risk of CKD progression.


Assuntos
Acetaminofen/efeitos adversos , Aspirina/efeitos adversos , Insuficiência Renal Crônica/induzido quimicamente , Acetaminofen/administração & dosagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Biomarcadores , Creatinina/sangue , Complicações do Diabetes , Progressão da Doença , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/prevenção & controle , Estudos Retrospectivos , Fatores de Risco
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