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2.
Lipids Health Dis ; 23(1): 52, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378566

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is closely linked to metabolic syndrome, characterised by insulin resistance, hyperglycaemia, abnormal lipid metabolism, and chronic inflammation. Diabetic ulcers (DUs) comprise consequential complications that arise as a result of T2DM. To investigate, db/db mice were used for the disease model. The findings demonstrated that a scaffold made from a combination of rhubarb charcoal-crosslinked chitosan and silk fibroin, designated as RCS/SF, was able to improve the healing process of diabetic wounds in db/db mice. However, previous studies have primarily concentrated on investigating the impacts of the RSC/SF scaffold on wound healing only, while its influence on the entire body has not been fully elucidated. MATERIAL AND METHODS: The silk fibroin/chitosan sponge scaffold containing rhubarb charcoal was fabricated in the present study using a freeze-drying approach. Subsequently, an incision with a diameter of 8 mm was made on the dorsal skin of the mice, and the RCS/SF scaffold was applied directly to the wound for 14 days. Subsequently, the impact of RCS/SF scaffold therapy on hepatic lipid metabolism was assessed through analysis of serum and liver biochemistry, histopathology, quantitative real-time PCR (qRT-PCR), immunohistochemistry, and Western blotting. RESULTS: The use of the RCS/SF scaffold led to an enhancement in the conditions associated with serum glucolipid metabolism in db/db mice. An assessment of hepatic histopathology further confirmed this enhancement. Additionally, the qRT-PCR analysis revealed that treatment with RCS/SF scaffold resulted in the downregulation of genes associated with fatty acid synthesis, fatty acid uptake, triglyceride (TG) synthesis, gluconeogenesis, and inflammatory factors. Moreover, the beneficial effect of the RCS/SF scaffold on oxidative stress was shown by assessing antioxidant enzymes and lipid peroxidation. Additionally, the network pharmacology analysis verified that the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway had a vital function in mitigating non-alcoholic fatty liver disease (NAFLD) by utilizing R. officinale. The measurement of AMPK, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) gene and protein expression provided support for this discovery. Furthermore, the molecular docking investigations revealed a robust affinity between the active components of rhubarb and the downstream targets of AMPK (SREBP1 and FASN). CONCLUSION: By regulating the AMPK signalling pathway, the RCS/SF scaffold applied topically effectively mitigated hepatic lipid accumulation, decreased inflammation, and attenuated oxidative stress. The present study, therefore, emphasises the crucial role of the topical RCS/SF scaffold in regulating hepatic lipid metabolism, thereby confirming the concept of "external and internal reshaping".


Assuntos
Quitosana , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Fibroínas , Hepatopatia Gordurosa não Alcoólica , Rheum , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Rheum/metabolismo , Carvão Vegetal/metabolismo , Carvão Vegetal/farmacologia , Carvão Vegetal/uso terapêutico , Fibroínas/metabolismo , Fibroínas/farmacologia , Fibroínas/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Simulação de Acoplamento Molecular , Úlcera/metabolismo , Úlcera/patologia , Fígado/metabolismo , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/patologia , Complicações do Diabetes/patologia , Inflamação/patologia , Ácidos Graxos/metabolismo , Lipídeos/uso terapêutico
3.
J Cutan Med Surg ; 28(1): 44-50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38156627

RESUMO

BACKGROUND: Pruritus is a common complaint in patients with end-stage renal disease. Indoxyl sulfate (IS) is a tryptophan end metabolite extremely renal excreted. Activated charcoal can interfere with IS intestinal absorption. OBJECTIVES: To evaluate the serum level of IS and the effect of activated charcoal on uremic pruritus. MATERIALS AND METHODS: In all, 135 participants were divided into 2 main groups. In total, 45 normal and healthy individuals as a control group and 90 patients on regular hemodialysis; 45 of these patients had uremic pruritus and the other 45 were not complaining of uremic pruritus. Serum IS was measured. Activated charcoal was used by patients with uremic pruritus. The severity of pruritus and Dermatology Life Quality Index (DLQI) were assessed. RESULTS: The serum IS was significantly elevated in uremic patients than in control subjects (P < .001) and significantly elevated in uremic patients without pruritus (P < .001). Furthermore, there were positive significant correlations between the serum IS and both severity of pruritus (P < .001) and DLQI (P < .001). After activated charcoal usage, there was a significant decrease in IS level with the improvement of pruritus and quality of life of patients. CONCLUSIONS: IS may play a role in uremic pruritus. Activated charcoal could be considered a treatment for uremic pruritus.


Assuntos
Carvão Vegetal , Uremia , Humanos , Carvão Vegetal/uso terapêutico , Uremia/complicações , Indicã , Qualidade de Vida , Prurido/tratamento farmacológico , Prurido/etiologia
4.
Clin J Am Soc Nephrol ; 18(9): 1210-1221, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37097121

RESUMO

Poisoning occurs after exposure to any of a number of substances, including medicines, which can result in severe toxicity including death. The nephrologist may be involved in poisonings that cause kidney disease and for targeted treatments. The overall approach to the poisoned patient involves the initial acute resuscitation and performing a risk assessment, whereby the exposure is considered in terms of the anticipated severity and in the context of the patient's status and treatments that may be required. Time-critical interventions such as gastrointestinal decontamination ( e.g. , activated charcoal) and antidotes are administered when indicated. The nephrologist is usually involved when elimination enhancement techniques are required, such as urine alkalinization or extracorporeal treatments. There is increasing data to guide decision making for the use of extracorporeal treatments in the poisoned patient. Principles to consider are clinical indications such as whether severe toxicity is present, anticipated, and/or will persist and whether the poison will be significantly removed by the extracorporeal treatment. Extracorporeal clearance is maximized for low-molecular weight drugs that are water soluble with minimal protein binding (<80%) and low endogenous clearance and volume of distribution. The dosage of some antidotes ( e.g. , N-acetylcysteine, ethanol, fomepizole) should be increased to maintain therapeutic concentrations once the extracorporeal treatment is initiated. To maximize the effect of an extracorporeal treatment, blood and effluent flows should be optimized, the filter with the largest surface area selected, and duration tailored to remove enough poison to reduce toxicity. Intermittent hemodialysis is recommended in most cases when an extracorporeal treatment is required because it is the most efficient, and continuous kidney replacement therapy is prescribed in some circumstances, particularly if intermittent hemodialysis is not readily available.


Assuntos
Intoxicação , Venenos , Humanos , Antídotos/uso terapêutico , Carvão Vegetal/uso terapêutico , Acetilcisteína/uso terapêutico , Etanol , Intoxicação/diagnóstico , Intoxicação/terapia
5.
Arch. pediatr. Urug ; 94(2): e309, 2023. graf
Artigo em Espanhol | LILACS, UY-BNMED, BNUY | ID: biblio-1520108

RESUMO

La intoxicación por paracetamol de causa no intencional en niños pequeños, e intencional en adolescentes es un motivo de consulta cada vez más frecuente en los servicios de urgencia. La gravedad y el pronóstico de esta intoxicación están dados por el riesgo de falla hepática. Ante la sospecha de ingesta de paracetamol, se debe conocer el tiempo transcurrido, la cantidad de ingesta del fármaco, estimar la toxicidad de la dosis ingerida para predecir hepatotoxicidad, determinar las medidas de contaminación necesarias, dosificar paracetamol en sangre y evaluar la necesidad de administración de antídoto. Se describe el caso de una adolescente que con intención suicida presentó una intoxicación aguda por paracetamol con riesgo de daño hepático requiriendo decontaminación digestiva, administración de antídoto y abordaje interdisciplinario de sus problemas psicoemocionales.


Paracetamol intoxication due to an unintentional cause in young children, and intentional in adolescents, is an increasingly frequent cause for consultation in emergency services. The severity and prognosis of this poisoning is due to the risk of liver failure. Given the suspicion of paracetamol ingestion, the time passed since the ingestion, the amount of paracetamol ingested, the estimate of the dose ingested to predict hepatotoxicity, we must determine the necessary decontamination measures and the paracetamol dose in blood and evaluate the need to administer a paracetamol antidote. We describe the case of an adolescent who presented acute paracetamol poisoning with risk of liver damage resulting from a suicide attempt and who required digestive decontamination, antidote administration and an interdisciplinary approach to her psychological and emotional problems.


A intoxicação não intencional por paracetamol em crianças pequenas e a intoxicação intencional em adolescentes é um motivo cada vez mais comum de consulta em serviços de emergência. A gravidade e o prognóstico desse envenenamento são dados pelo risco de insuficiência hepática. Quando há suspeita de ingestão de paracetamol, o tempo decorrido desde que é ingerido, a quantidade de paracetamol ingerida, a estimação da dose ingerida para predizer hepatotoxicidade, utilizamse para determinar as medidas de contaminação necessárias, dosar paracetamol no sangue e avaliar a ne- cessidade de administração de antídoto. Descrevemos o caso de uma adolescente com intenção suicida que apresentou intoxicação aguda por paracetamol com risco de lesão hepática com necessidade de descontaminação digestiva, administração de antídoto e abordagem interdisciplinar de seus problemas psicoemocionais.


Assuntos
Humanos , Feminino , Criança , Intoxicação/tratamento farmacológico , Carvão Vegetal/uso terapêutico , Acetaminofen/envenenamento
6.
Am J Emerg Med ; 60: 57-61, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35907270

RESUMO

BACKGROUNDS: Delayed neurological sequelae (DNS) are a severe complication of carbon monoxide poisoning (COP) and high predisposing rates of disability and mortality, yet the relationship between exposure factors and DNS remains unknown. The aim was to investigate the association between domestic sources of COP and DNS. METHODS: Patients diagnosed with COP between December 2016 and November 2021 were included and divided into two groups according to their sources of poisoning and the endpoint outcome was analyzed by logistic regression before and after propensity score matching (PSM). RESULTS: Overall, medical data from 314 patients were analyzed. In multivariate logistic regression, advanced age (adjusted odds ratio (AOR): 1.028, 95% CI: 1.008-1.049, P = 0.007), longer duration of exposure to the first treatment of hyperbaric oxygen (HBO) (AOR: 1.081, 95% CI: 1.036-1.127, P = 0.001), and intoxication by charcoal burning (AOR: 3.24, 95% CI: 1.208-8.69, P = 0.019) were associated with a higher risk of developing DNS. After 1:1 PSM, the outcomes also revealed that charcoal burning intoxication (odds ratio (OR): 8.396, 95% CI: 3.342-21.095, P<0.001) was associated with greater odds of DNS. CONCLUSIONS: This study indicates that domestic COP caused by charcoal burning is more likely to trigger DNS than gas-emitting heaters.


Assuntos
Intoxicação por Monóxido de Carbono , Leucemia Mieloide Aguda , Acidentes , Intoxicação por Monóxido de Carbono/complicações , Intoxicação por Monóxido de Carbono/terapia , Carvão Vegetal/uso terapêutico , Progressão da Doença , Humanos , Leucemia Mieloide Aguda/complicações , Estudos Retrospectivos
7.
J Mater Chem B ; 9(10): 2447-2456, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33630987

RESUMO

Exploiting new non-metal-based peroxidase-mimic nanoenzymes for chemodynamic therapy (CDT) in cancer treatment is an active and challenging field. Here, we found that activated carbon nanoparticles (denoted as ANs) fabricated from coconut shell have satisfactory peroxidase-mimic nanoenzyme activity. Based on this positive result, gadodiamide, a clinically used nuclear magnetic imaging contrast agent, was loaded inside the AN pores and encapsulated by polyvinylpyrrolidone (PVP) to obtain Gd@PANs. PANs (ANs modified using PVP) efficiently catalyze the massive decomposition of endogenous hydrogen peroxide (H2O2) inside cancer cells to produce toxic oxidized hydroxyl radicals (˙OH) for the CDT treatment of cancer, but they showed no toxicity toward normal cells. Additionally, under 808 nm laser irradiation, the photothermal conversion efficiency of the PANs reaches 45.20%, ensuring their effective photothermal therapy (PTT) treatment functionality. Simultaneously, during PTT treatment, the heating effect significantly enhances the peroxidase-mimic activity of the PANs to achieve an ideal PTT-CDT synergistic therapeutic outcome. Gd@PANs can also be used for the T1-magnetic resonance imaging (MRI) of tumors to integrate treatment and diagnosis.


Assuntos
Carvão Vegetal/química , Carvão Vegetal/farmacologia , Cocos/química , Fototerapia/métodos , Linhagem Celular Tumoral , Carvão Vegetal/uso terapêutico , Terapia Combinada , Temperatura Alta , Humanos , Peróxido de Hidrogênio/metabolismo , Lasers
8.
Eur J Clin Pharmacol ; 77(6): 809-815, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33388821

RESUMO

PURPOSE: Paracetamol is the only drug recommended to treat fever in neonates. At recommended doses, paracetamol has not been associated with liver injury in neonates, while hepatotoxicity may occur after intake of a single high dose or multiple excessive doses. The aim of this narrative review is to critically analyze and summarize the available literature on newborns and infants exposed to supratherapeutic doses of paracetamol, with special focus on their clinical features, outcome, and management. METHODS: The PubMed, SCOPUS, and Google Scholar search engines were used to collect data, without time limitation. The following keywords were used: paracetamol/acetaminophen, overdose, hepatotoxicity, N-acetylcysteine, newborn, infant. RESULTS: The literature search identified a total of 27 case reports, a number of review articles, and few other relevant publications. Neonatal poisoning from paracetamol resulted from transplacental drug transfer after maternal overdose in some published cases, while it was the consequence of medication errors in other cases. Newborns and infants who have received a single overdose and have paracetamol concentrations below the Rumack-Matthew nomogram limits are at low risk of serious hepatic damage, while those who have recently ingested more than one supratherapeutic dose of paracetamol should be managed with caution. The treatment of choice for paracetamol poisoning is N-acetylcysteine, a specific antidote which reduces paracetamol hepatotoxic effects. N-Acetylcysteine should be given according to specific regimens through weight-based dosing tables. CONCLUSIONS: Caution should be used when paracetamol is administered to the newborn. In the event of an overdose, careful patient monitoring and personalization of post-overdose procedures are recommended.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Antídotos/uso terapêutico , Overdose de Drogas/fisiopatologia , Acetilcisteína/uso terapêutico , Carvão Vegetal/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Overdose de Drogas/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia
9.
Acta pediátr. hondu ; 12(2): 1279-1282, oct. 2021-marz. 2022.
Artigo em Espanhol | LILACS, BIMENA | ID: biblio-1435809

RESUMO

La intoxicación por betabloqueadores es una situación clínica de poca frecuencia, estrechamente relacionada con trastornos depresivos mayores, con una prevalencia mayor en mujeres. Los episodios de gravedad relacio- nados a toxicidad por betabloqueadores son clasificados como episodios de moderados a severos. En el caso del carvedilol con un umbral tóxico de 50mg. Caso Clínico: Paciente de 16 años con historia de ingesta de carvedilol en niveles tóxicos y único antecedente depresión ma- yor. Discusión: Los betabloqueadores antagonizan los receptores betaadrenérgicos, la sintomatología relacio- nada con bradicardia e hipotensión es frecuente y puede generar afección a nivel del sistema nervioso central. El tratamiento de emergencia sí se capta al paciente en la primera hora consiste en realizar un lavado gástrico y aplicar carbón activado. Se propone el uso de crista- loides y el uso de epinefrina o norepinefrina como ma- nejo de primera línea, en caso de bradicardias sosteni- das debe considerarse el uso de atropina. Los pacientes asintomáticos deben ser vigilados durante seis horas...(AU)


Assuntos
Humanos , Masculino , Adolescente , Antagonistas Adrenérgicos beta/toxicidade , Carvedilol/toxicidade , Atropina/uso terapêutico , Carvão Vegetal/uso terapêutico
10.
Am J Emerg Med ; 38(11): 2491.e1-2491.e2, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32826106

RESUMO

Presenting a case of acute theophylline and salbutamol overdose with distributive shock. Twenty one years old lady presented with history of consumption of 3 gram of theophylline and 40 mg of salbutamol. On admission she had altered sensorium with the systolic blood pressure of 60 mmHg, unrecordable diastolic blood pressure and heart rate of 147/min. Investigations revealed severe metabolic acidosis, hypokalemia, hypocalcemia which was managed by intravenous fluids, vasopressors, infusion of injection calcium gluconate and injection potassium chloride. As her hemodynamic status did not improve, she has been initiated on 1.5 mL/kg of lipid emulsion as bolus and then 0.5 mL/kg/h as infusion. Her hemodynamic status improved gradually and she was discharged in 24 h. Lipid emulsion had been used in local anesthetics and many tablet overdoses. In this patient timely administration of lipid emulsion resulted in early recovery of shock.


Assuntos
Acidose/induzido quimicamente , Broncodilatadores/envenenamento , Overdose de Drogas/terapia , Emulsões Gordurosas Intravenosas/uso terapêutico , Hidratação , Choque/induzido quimicamente , Teofilina/envenenamento , Vasoconstritores/uso terapêutico , Acidose/terapia , Albuterol , Gluconato de Cálcio/uso terapêutico , Carvão Vegetal/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Hipocalcemia/induzido quimicamente , Hipocalcemia/terapia , Hipopotassemia/induzido quimicamente , Hipopotassemia/terapia , Cloreto de Potássio/uso terapêutico , Choque/terapia , Adulto Jovem
11.
Cochrane Database Syst Rev ; 7: CD000493, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32716060

RESUMO

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013. OBJECTIVES: To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, including cluster-randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy. DATA COLLECTION AND ANALYSIS: The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo-controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S-adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) -7.64 points, 95% confidence interval (CI) -9.69 to -5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy. AUTHORS' CONCLUSIONS: When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low-certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high-quality trials of other interventions are needed in order to identify effective treatments for maternal itching and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).


Assuntos
Colestase/terapia , Complicações na Gravidez/terapia , Prurido/terapia , Carvão Vegetal/uso terapêutico , Colagogos e Coleréticos/uso terapêutico , Colestase/complicações , Resina de Colestiramina/uso terapêutico , Dexametasona/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Sofrimento Fetal/epidemiologia , Galactanos/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Mananas/uso terapêutico , Gomas Vegetais/uso terapêutico , Gravidez , Prurido/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , S-Adenosilmetionina/uso terapêutico , Natimorto/epidemiologia , Ácido Ursodesoxicólico/uso terapêutico
12.
Pulm Pharmacol Ther ; 61: 101902, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045673

RESUMO

BACKGROUND: Indacaterol is one of the long-acting beta2-adrenergic agonists, referred as first-line monotherapy for Chronic obstructive pulmonary disease since 2011. Generic products are encouraged to benefit the large COPD patients in China, in which can provide more choices association with reduced cost and improve the quality of patient life. OBJECTIVE: The three-part study consists of two independent cohorts of thirty-six subjects, aimed to evaluate the bioequivalence (BE) of two indacaterol formulations in gastrointestinal (GI) absorption charcoal-block or non-block conditions. One pilot study performed in six healthy subjects to determine the blocking effect of a new charcoal-based regimen on GI absorption after orally inhalation of indacaterol. METHODS: Two BE studies were conducted with a randomized, open-label, 2-period crossover design in two independent 36-healthy-subject cohorts, equivalence in systemic and lung deposition was assessed after inhalation of a single dose of 150 µg indacaterol (test or reference formulation) alone or concomitant administration of charcoal. The charcoal-based regimen was improved by optimizing the dose and number of doses, and its blocking efficacy against GI absorption was assessed in a pilot study. Six healthy subjects received 9 g charcoal 10 min before, immediately after and 2 h after indacaterol (3 g/100 ml water × 3 times). Blood collected at predetermined time points up to 72 h. Plasma indacaterol concentrations were determined using HPLC-MS/MS. Pharmacokinetics parameters were calculated with non-compartment analysis. Equivalences were concluded if the 90% confidence interval (CI) for test: reference of Cmax and AUC0-t fell within the limits of 0.8-1.25. RESULTS: Indacaterol was undetectable in plasma samples in pilot study. The T/R ratio of the geometric mean Cmax and AUC0-t was 109.9% (90% CI, 106.1-113.8%) and 104.8% (90% CI, 101.5-108.1%) for charcoal-block subjects and 105.4% (90% CI, 99.8% ~ 111.3%), and 101.0% (90% CI, 97.7%-104.4%) for non-block subjects. No serious adverse events were reported. CONCLUSIONS: The results showed that 150 µg indacaterol (+/- 9 g charcoal) was well tolerated in all subjects. The two formulations are bioequivalent in terms of the rate and absorption both in charcoal-block and non-block conditions. The improved charcoal-based regimen demonstrated to be effective and fully blockade of GI absorption of indacaterol.


Assuntos
Carvão Vegetal/uso terapêutico , Indanos/administração & dosagem , Indanos/farmacocinética , Quinolonas/administração & dosagem , Quinolonas/farmacocinética , Administração por Inalação , Adulto , Povo Asiático , Estudos Cross-Over , Composição de Medicamentos , Feminino , Humanos , Indanos/efeitos adversos , Masculino , Maleatos , Pessoa de Meia-Idade , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/efeitos adversos , Equivalência Terapêutica , Adulto Jovem
13.
Med J Aust ; 212(4): 175-183, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31786822

RESUMO

INTRODUCTION: Paracetamol is a common agent taken in deliberate self-poisoning and in accidental overdose in adults and children. Paracetamol poisoning is the commonest cause of severe acute liver injury. Since the publication of the previous guidelines in 2015, several studies have changed practice. A working group of experts in the area, with representation from all Poisons Information Centres of Australia and New Zealand, were brought together to produce an updated evidence-based guidance. MAIN RECOMMENDATIONS (UNCHANGED FROM PREVIOUS GUIDELINES): The optimal management of most patients with paracetamol overdose is usually straightforward. Patients who present early should be given activated charcoal. Patients at risk of hepatotoxicity should receive intravenous acetylcysteine. The paracetamol nomogram is used to assess the need for treatment in acute immediate release paracetamol ingestions with a known time of ingestion. Cases that require different management include modified release paracetamol overdoses, large or massive overdoses, accidental liquid ingestion in children, and repeated supratherapeutic ingestions. MAJOR CHANGES IN MANAGEMENT IN THE GUIDELINES: The new guidelines recommend a two-bag acetylcysteine infusion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h). This has similar efficacy but significantly reduced adverse reactions compared with the previous three-bag regimen. Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine. All potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine. Patients ingesting ≥ 30 g or ≥ 500 mg/kg should receive increased doses of acetylcysteine.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/administração & dosagem , Analgésicos não Narcóticos/envenenamento , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Overdose de Drogas/terapia , Administração Intravenosa , Antídotos/uso terapêutico , Austrália , Carvão Vegetal/uso terapêutico , Humanos , Nova Zelândia , Guias de Prática Clínica como Assunto
14.
J Vet Emerg Crit Care (San Antonio) ; 30(1): 74-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31883205

RESUMO

OBJECTIVE: To describe the treatment and clinical course of a dog accidentally prescribed 10 times the recommended dose of colchicine (0.3 mg/kg/d instead of 0.03 mg/kg/d). CASE SUMMARY: After glaucoma surgery, a 1-year-old male neutered Pomeranian weighing 6.8 kg was prescribed 1,000 µg colchicine twice a day per os. The dog presented to the emergency department after the first dose with vomiting and was treated as an outpatient. Two colchicine doses later, the dog represented with vomiting, ocular pain, and increased intraocular pressure. The dog's vital signs were normal, and the dog was admitted for rehydration, analgesia, and revision glaucoma surgery the next day. Two hours after revision surgery, the dog developed vomiting and diarrhea. Postoperatively, the dog was hypothermic (36.3°C), persistently hypertensive (227 mm Hg), and bradycardic (60/min). Biochemistry revealed metabolic acidosis and increased hepatic enzyme activities. Mannitol was administered for presumed cerebral edema. Later, the dog developed bradycardia due to second-degree atrioventricular heart block, which responded to atropine. Total hospitalization was 9 days. Treatment included IV fluids, IV lipid emulsion, N-acetylcysteine, activated charcoal, gastroprotectants, antiemetics, opioids, antimicrobials, and barrier nursing due to transient neutropenia. NEW OR UNIQUE INFORMATION PROVIDED: This is the first report to describe the successful treatment of a dog with colchicine overdose. The systemic effects were presumed to be secondary to colchicine toxicosis rather than diet, infection, or other drug reaction, and may have been compounded by a second anesthetic episode. Gastrointestinal signs, symptoms of cerebral edema, cardiac arrhythmias, and neutropenia were documented. One other report of colchicine overdose in a dog exists, and that patient was euthanized. This report demonstrates that complete recovery with intensive care is possible; however, the prognosis remains guarded.


Assuntos
Colchicina/envenenamento , Doenças do Cão/diagnóstico , Animais , Bradicardia/etiologia , Bradicardia/veterinária , Carvão Vegetal/uso terapêutico , Cuidados Críticos , Diarreia/etiologia , Diarreia/veterinária , Doenças do Cão/sangue , Doenças do Cão/terapia , Cães , Overdose de Drogas/complicações , Overdose de Drogas/veterinária , Hidratação/veterinária , Glaucoma/cirurgia , Glaucoma/veterinária , Masculino , Complicações Pós-Operatórias/veterinária , Vômito/etiologia , Vômito/veterinária
15.
BMC Cancer ; 19(1): 859, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470821

RESUMO

BACKGROUND: We report on our experience of ultrasound (US)-guided dual-localization for axillary nodes before and after neoadjuvant chemotherapy (NAC) with clip and activated charcoal to guide axillary surgery in breast cancer patients. METHODS: Between November 2017 and May 2018, a dual-localization procedure was performed under US guidance for the most suspicious axillary nodes noted at initial staging (before NAC, with clip) and restaging (after NAC, with activated charcoal) in 28 cytologically proven node-positive breast cancer patients. Patients underwent axillary sampling or dissection, which involved removing not only the sentinel nodes (SNs), but also clipped nodes (CNs) and tattooed nodes (TNs). Success (or failure) rates of biopsies of SNs, CNs, and TNs and inter-nodal concordance rates were determined. Sensitivities for the individual and combined biopsies were calculated. RESULTS: SN biopsy failed in four patients (14%), whereas the CN biopsy failed in one patient (4%). All TNs were identified in the surgical field. Concordance rates were 79% for CNs-TNs, 63% for CNs-SNs, and 58% for TNs-SNs. Sensitivity for SN, CN, and TN biopsy was 73%, 67%, and 67%, respectively. Sensitivity was 80% for any combination of biopsies (SN plus CN, SN plus TN, SN plus CN plus TN). CONCLUSIONS: US-guided dual-localization of axillary nodes before and after NAC with clip and activated charcoal was a feasible approach that might facilitate more reliable nodal staging with less-invasive strategies in node-positive breast cancer patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carvão Vegetal/administração & dosagem , Metástase Linfática/diagnóstico por imagem , Biópsia de Linfonodo Sentinela/métodos , Adulto , Idoso , Axila , Neoplasias da Mama/diagnóstico por imagem , Carvão Vegetal/uso terapêutico , Tratamento Farmacológico , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Sensibilidade e Especificidade , Ultrassonografia de Intervenção
16.
Tidsskr Nor Laegeforen ; 139(9)2019 May 28.
Artigo em Norueguês, Inglês | MEDLINE | ID: mdl-31140247

RESUMO

BACKGROUND: A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before admission and had been cardioverted a few days after the procedure because of relapse of atrial fibrillation. CASE PRESENTATION: On admission, the patient had systolic blood pressure of 80 mm Hg and an ECG with broad QRS-complexes at 380 ms. We suspected intoxication and she was intubated to administer activated charcoal after gastric lavage. She was cardiovascularly unstable and in need of intravenous infusion of noradrenaline and adrenaline. Further investigations at her home suggested that she had poisoned herself with 4-5 g flecainide, 0.3 g oxazepam and 0.5 g meclizine. After administration of 500 mmol sodium bicarbonate and 5 mmol calcium chloride, the QRS complexes narrowed temporarily. On day 2, due to sustained bradycardia and hypotension despite receiving adrenergic medications, a temporary pacemaker was implanted, leading to improved heart rate and blood pressure. She experienced several complications including hypertensive pulmonary oedema, atrial fibrillation, extensively prolonged QT interval because of polypharmacy and Takotsubo cardiomyopathy. She was discharged from the hospital in good health on day 17. At a follow-up visit at the outpatient clinic 12 weeks later, cardiac function had normalised. The QT interval was now normal; however, there were persistent T-wave inversions in leads I, aVL and V4-6. INTERPRETATION: Flecainide blocks sodium channels in cardiomyocytes. Intoxication with flecainide is rare, with mortality rates of about 10 %. Sodium bicarbonate in larger doses has been reported to stabilise patients with flecainide intoxication due to modification of the binding of flecainide to sodium receptors in cardiomyocytes, and due to alkalisation which makes flecainide detach from sodium receptors. Our patient had a temporary effect with narrowing of QRS complexes after receiving sodium bicarbonate. She also showed a beneficial effect from implantation of a temporary pacemaker, although earlier case reports have described problems with high thresholds and capture failure.


Assuntos
Antiarrítmicos/envenenamento , Overdose de Drogas , Flecainida/envenenamento , Carvão Vegetal/uso terapêutico , Overdose de Drogas/complicações , Overdose de Drogas/terapia , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Marca-Passo Artificial , Choque/induzido quimicamente , Choque/terapia , Sonolência , Bicarbonato de Sódio/uso terapêutico
17.
Vet Clin Pathol ; 48(1): 67-70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30924544

RESUMO

A 4-year-old, spayed female French Bulldog was presented for respiratory distress and suspected aspiration pneumonia after oral administration of activated charcoal for possible ingestion of a suspected toxic dose of trazodone. The patient had a moderate volume of pleural effusion, which contained free and intracellular black particulate matter consistent with charcoal. Due to presumed charcoal aspiration with subsequent lung rupture, the right middle and right caudal lung lobes were surgically removed. Histology revealed abundant black debris consistent with charcoal and severe granulomatous inflammation. Based on the clinical, gross, and histologic findings, a diagnosis of severe, chronic, locally extensive, aspiration pneumonia and lung rupture with secondary pleuritis and mediastinitis due to charcoal aspiration was made. Aspiration pneumonia is the main complication of activated charcoal administration, which can incite extensive, granulomatous inflammation in the respiratory tract. To the authors' knowledge, this is the first report describing the cytologic and histologic findings associated with inadvertent charcoal aspiration in a veterinary species.


Assuntos
Carvão Vegetal/efeitos adversos , Doenças do Cão/patologia , Lesão Pulmonar/veterinária , Pneumonia Aspirativa/veterinária , Animais , Carvão Vegetal/uso terapêutico , Doenças do Cão/cirurgia , Cães , Feminino , Granuloma/patologia , Granuloma/veterinária , Pulmão/patologia , Pulmão/cirurgia , Lesão Pulmonar/cirurgia , Derrame Pleural/patologia , Derrame Pleural/veterinária , Pneumonia Aspirativa/diagnóstico , Pneumonia Aspirativa/patologia , Trazodona/envenenamento
18.
Medicine (Baltimore) ; 97(30): e11669, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30045322

RESUMO

RATIONALE: Paraquat, an agent highly toxic to humans and animals, is a widely used herbicide and also commonly used for suicide attempts in Taiwan. The most common route of intoxication is oral ingestion, and parenteral poisoning is respectively rare. PATIENT CONCERNS: A 39-year-old illicit abuser of heroin and amphetamine injected 0.5 mL of 24% paraquat directly into his right cephalic vein due to hallucination. The patient was brought to our emergency department for management 4 hours after injection. He was fully conscious and had normal vital signs. Systemic review showed mild dyspnea, abdominal pain and right wrist pain over the injection site. The only abnormal physical finding was erythema over the injection site and epigastric tenderness. DIAGNOSIS: Laboratory investigations, including complete blood count, liver and renal function, and electrolytes initially yielded normal results. Urinalysis showed normal findings except a positive urine paraquat test (4+). The initial plasma paraquat concentration was 0.51 µg/mL. INTERVENTIONS: He was admitted to the intensive care unit and underwent one session of charcoal hemoperfusion therapy. Acute kidney injury developed on the fourth day after intoxication, with the level of serum creatinine rising rapidly from 0.96 to 4.57 mg/dL and the daily urine output decreased noticeably from > 2000 to 900 mL. The serum creatinine level improved gradually with adequate fluid supplementation. OUTCOMES: The patient was discharged 13 days later in a stable condition. LESSONS: Intravenous paraquat intoxication is rare. Patients who suffer from intravenous intoxication may not directly suffer from mucosal irritation, but the clinical onset of systemic effects is more immediate and lethal. The prognosis of paraquat poisoning is determined by the time of poisoning and the plasma paraquat concentration before treatment. Proudfoot's curve provides a simple method of predicting the survival rate. The most effective mode of management is extracorporeal therapy, and immunosuppressive or antioxidant therapies have shown insufficient evidence of benefit.


Assuntos
Paraquat/envenenamento , Injúria Renal Aguda/induzido quimicamente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Antídotos/uso terapêutico , Carvão Vegetal/uso terapêutico , Alucinações/complicações , Hemoperfusão , Dependência de Heroína/complicações , Humanos , Injeções Intravenosas , Masculino , Paraquat/administração & dosagem , Paraquat/sangue , Intoxicação/terapia , Resultado do Tratamento
19.
J Crit Care ; 46: 17-22, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29627659

RESUMO

Amanita phalloides poisoning with a high mortality is a serious health problem in the world. The typical clinical manifestations are usually characterized by the absence of any symptoms followed by severe gastrointestinal disorders and acute liver failure. Inhibition of RNA polymeraseII (RNAP II) activity, apoptosis, and oxidative stress are considered as the major mechanism of amatoxins intoxication. The current treatment measures mainly include prevention of amatoxins absorption, elimination of absorbed amatoxins, potential antidotes therapy, and liver transplantation. Nevertheless, there are no widely accepted treatment criteria for Amanita phalloides poisoning. This paper will focus on the treatment measures based on the previous studies and provide the currently available information for clinicians.


Assuntos
Amanita , Amanitinas/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Fígado/efeitos dos fármacos , Intoxicação Alimentar por Cogumelos/terapia , Acetilcisteína/uso terapêutico , Antídotos/uso terapêutico , Ductos Biliares/efeitos dos fármacos , Carvão Vegetal/uso terapêutico , Diurese , Lavagem Gástrica , Humanos , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Intoxicação Alimentar por Cogumelos/epidemiologia , Penicilina G/uso terapêutico , Silimarina/uso terapêutico
20.
Acta Paediatr ; 107(10): 1775-1780, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29577416

RESUMO

AIM: This study focused on children aged zero to six years with suspected single-dose paracetamol poisoning, which has not been investigated in Denmark. We evaluated the incidence of liver injuries and the use of activated charcoal and N-acetylcysteine treatment. METHODS: Our retrospective study was performed in three paediatric hospital centres from 2001 to 2012. Data on symptoms, time of ingestion, blood biochemistry, treatment and adverse reactions were collected. The results were evaluated against the Rumack-Matthew nomogram. RESULTS: We identified 221 children (58% male), with a mean age of 2.67 ± 1.05 years. Activated charcoal treatment was given in 87% of cases, but only 15% of the children received treatment within one hour of the suspected paracetamol poisoning. Although 80% of the children received N-acetylcysteine treatment, only one case (0.5%) had a toxic plasma paracetamol level according to the treatment nomogram. Abdominal pain or vomiting was associated with higher paracetamol levels in plasma. None of the children developed liver injuries. CONCLUSION: We found a low incidence of significant poisoning and liberal use of N-acetylcysteine and activated charcoal treatment in Danish children aged zero to six years with suspected paracetamol poisoning. Vomiting or abdominal pain was associated with elevated plasma paracetamol levels. No liver injuries were reported.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/uso terapêutico , Analgésicos não Narcóticos/envenenamento , Carvão Vegetal/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Antídotos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos
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