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Papulosquamous lesions in an elderly female with multiple co-morbidities often pose diagnostic challenge. We present an interesting case of anti-tubercular treatment (ATT) induced sub-acute cutaneous lupus erythematosus. The patient presented with papulosquamous lesions in generalised distribution, which showed interface dermatitis on histopathology. The serology for anti-nuclear antibodies, anti-Ro and anti-La was positive. The rash resolved spontaneously after stopping all the suspected drugs. Oral provocation was performed with first line anti-tubercular drugs and ethambutol was found to be the culprit drug, which was later confirmed by reappearance of skin rash by inadvertent ingestion of one dose of ethambutol by the patient.
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The term "gynecomastia" refers to the benign growth of glandular breast tissue in men. In older men, adolescents, and newborns, physiological gynecomastia is common. Although it is self-limited, it can be managed to reduce both physical and emotional discomfort. Chronic conditions (such as cirrhosis, hypogonadism, and renal insufficiency), drug use (including prescription, over-the-counter, and illicit drugs), and tumors are rare causes of nonphysiologic gynecomastia. Exogenous estrogens, antiandrogens, 5-alpha reductase inhibitors, spironolactone, and cimetidine are the active ingredients that are known to cause gynecomastia the most frequently. A patient's medical history is crucial in diagnosing drug-induced gynecomastia. Treating the underlying disease and stopping contributing medications are the cornerstones of treatment. In certain cases, gynecomastia can be treated with surgery and medications such as estrogen receptor modulators. Early intervention and patient-directed care are important aspects of treatment. We describe the pathogenetic mechanism of spironolactone-induced gynecomastia and provide a case report of a 52-year-old male patient.
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La hepatotoxicidad inducida por medicamentos es un diagnóstico de descarte. Típicamente, se presenta en pacientes que desarrollan cambios clínicos y bioquímicos compatibles con hepatitis, pero relacionados con el inicio reciente de agentes farmacológicos, y que se resuelven tras el retiro de la noxa. Su desarrollo se ha descrito con el uso de algunos antibióticos, antituberculosos, estatinas, herbolarios y antiinflamatorios no esteroideos; sin embargo, hay pocos reportes de casos con el uso de anticonceptivos orales, en los cuales el surgimiento de mecanismos idiosincráticos puede llevar a la presentación de características clínicas como ictericia y anormalidades en los exámenes de laboratorio, como la elevación de las transaminasas. Esto requiere de estudios extensos para descartar otras patologías que pueden presentarse de esta forma, lo que representa un reto clínico. En este artículo se muestra el reporte de un caso de una paciente con antecedente de uso crónico de anticonceptivos implantables y que, tras el ajuste de la terapia con el inicio de anticonceptivos orales, desarrolla un episodio de elevación marcada de transaminasas e ictericia.
Drug-induced liver injury is a rule-out diagnosis. Typically, it occurs in patients who develop clinical and biochemical changes compatible with hepatitis, but related to a history of recent onset of pharmacological agents, and resolves after withdrawal of the noxious substances. Its development has been described with the use of some antibiotics, antituberculosis agents, statins, herbal and nonsteroidal anti inflammatory drugs; however, there are few reports of cases with the use of oral contraceptives, in which the appearance of idiosyncratic mechanisms can lead to the presentation of clinical features such as jaundice and laboratory tests abnormalities, like transaminase elevation, requiring extensive studies to rule out other pathologies that may have this clinical presentation, wich represents a clinical challenge. We present a case report of a patient who had chronic use of implantable contraceptives and who, after adjustment of therapy with the start of oral contraceptives, developed an episode of marked elevation of transaminases and jaundice.
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Tanto la lesión hepática inducida por drogas (DILI), así como la lesión hepática inducida por hierbas (HILI), son una preocupación creciente en la atención sanitaria contemporánea que plantea importantes desafíos clínicos debido a sus variadas etiologías, presentaciones clínicas y posibles resultados potencialmente mortales. Presentamos el caso de un paciente masculino de 38 años con antecedentes de cálculos renales que consultó por dolor lumbar y hematuria. Al ingreso presentó ictericia, hepatomegalia, dolor a la palpación en fosa ilíaca derecha y no tenía signos de hepatopatía crónica, con pruebas de función hepática anormales, que mostraron un patrón hepatocelular asociado con hiperbilirrubinemia. Se descartó obstrucción biliar, trombosis portal, hepatitis autoinmune y viral, con panel autoinmune negativo. El paciente refirió haber consumido un remedio herbario para los cálculos renales llamado "vino rompe cálculos (chancapiedra)", que se supone contiene Phyllanthus niruri, cinco días antes del inicio de los síntomas. Una biopsia hepática reveló hepatitis aguda con infiltrado inflamatorio mixto. Debido al empeoramiento de las pruebas de función hepática y la sospecha de DILI idiosincrásico, se inició un ensayo terapéutico con corticosteroides, que resultó en una mejoría clínica y del perfil hepático. La gravedad de este caso nos recuerda la necesidad de incrementar el seguimiento por parte de las autoridades reguladoras de medicamentos, implementar campañas educativas para los pacientes e informar a la comunidad sobre productos con alertas activas.
Both drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are a growing concern in contemporary healthcare that poses significant clinical challenges due to their varied etiology, clinical presentations, and potential life-threatening outcomes. We present the case of a 38-year-old male patient with a history of kidney stones who consulted for low back pain and hematuria. On admission he presented with jaundice, hepatomegaly, pain on palpation in the right iliac fossa and no signs of chronic liver disease, with abnormal liver function tests, which showed a hepatocellular pattern associated with hyperbilirubinemia. Biliary obstruction, portal thrombosis, autoimmune and viral hepatitis were ruled out, with negative autoimmune panel. The patient reported consuming an herbal remedy for kidney stones called "stone-breaking wine (chancapiedra)", presumed to contain Phyllanthus niruri, five days before the onset of symptoms. A liver biopsy revealedacute hepatitis with mixed inflammatory infiltrate. Due to worsening liver function tests and suspicion of idiosyncratic DILI, a therapeutic trial with corticosteroids was initiated, which resulted in clinical and liver profile improvement. The severity of this case reminds us of the need to increase follow-up by drug regulatory authorities, implement educational campaigns for patients, and inform the community about products with active alerts.
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Objective To analyze the clinical characteristics of 310 patients with anti-tuberculosis drug-induced liver injury(ATB-DILI),to explore prognostic influencing factors,and to provide reference for its prevention and treatment.Methods Primary tuberculosis patients hospitalized in the Department of Tuberculosis of the Third People's Hospital of Kunming from November 2020 to November 2022 who met the diagnosis of ATB-DILI were enrolled.Statistics by gender,age,history,type of tuberculosis,co-morbidities,frequency of anti-tuberculosis regimens leading to liver injury,use of hepatoprotective drugs,and management and regression were performed to analyze the clinical characteristics of the patients and the factors influencing their prognosis.Results 310 patients were included,male,148(47.74%)and female,162(52.26%).The mean age was 44.33±17.47 years.Thirty-four patients had a history of allergy.The combination of isoniazid,rifampicin,pyrazinamide,and ethambutol(244 patients,78.71%)was the anti-tuberculosis regimen that resulted in the highest number of cases of hepatic injury.The median time between initiation of the tuberculosis regimen and the development of hepatic injury in patients with ATB-DILI was 30 d,and the mean duration of hospitalization was 16.39±7.01 d.The most used hepatoprotective drug was reduced glutathione(154 patients,49.68%),and most patients used a combination of 2 hepatoprotective drugs(128 patients,41.29%).Liver injury improved in 257 cases(82.90%)and failed in 53 cases(17.10%).The differences in alcohol consumption,severity,clinical staging,TT,ALP,TBIL,DBIL,IBIL,and GGT were statistically significant compared to those who did not recover(P<0.05),and severity and high ALP were independent risk factors for poor prognosis.Conclusions Patients should be carefully asked if they have a history of basic liver disease and alcoholism before using anti-tuberculosis drugs.In the course of anti-tuberculosis treatment,the combined use of anti-tuberculosis drugs is more serious than the use of single drugs to cause liver damage.Drugs that may cause liver damage should be used with caution and improved anti-tuberculosis programs should be explored.At the same time,liver function should be monitored regularly during anti-tuberculosis treatment,especially 30 days after medication,in order to reduce the occurrence of adverse reactions.
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Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58％).7 catego-ries of drugs induced DILI,with herbal ranking first(52％).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62％)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27％).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.
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Recognizing upper airway obstruction and stenosis is critical to determine the subsequent treatment options in patients with obstructive sleep apnea(OSA).Drug-induced sleep endoscopy(DISE)is a 3D visual evaluation technology for the anatomical structure of the upper respiratory tract of OSA patients during"sleeping"state after being anesthetized.The dynamic situation of upper respiratory tract obstruction and collapse can be observed safely and quickly through endoscopy,which provides important reference for formulating surgical methods and positive airway pressure(PAP)intervention treatments.With the assistance of polysomnography(PSG),DISE plays an important role in optimizing individualized treatment plans for OSA.The present article introduces the technical operating points of PSG-assisted drug-induced sleep endoscopic positive airway pressure titration.
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ObjectiveTo determine the scores of patients with a confirmed diagnosis of drug-induced liver injury （DILI） using Roussel Uclaf Causality Assessment Method （RUCAM）， Maria ＆ Victorino assessment scale， and Revised Electronic Causality Assessment Method （RECAM）， to compare the accuracy of the three scales in diagnosis， and to investigate their clinical significance in the diagnosis of DILI. MethodsA total of 98 patients with a confirmed diagnosis of DILI who were hospitalized in Peking University First Hospital from January 2011 to December 2022 were enrolled， with liver biopsy results supporting DILI and a clear history of medication. Clinical data were collected from all subjects， and the above causality assessment scales were used for scoring. The chi-square test was used to analyze the diagnostic accuracy of the causality assessment scales， and the weighted kappa coefficient was used to analyze the consistency between the three scales. ResultsFor all patients with DILI enrolled， RECAM had the highest accuracy， with a significant difference compared with RUCAM （χ2=5.667，P=0.017）. RUCAM and RECAM had moderate consistency in diagnosis （κw=0.469）， while RECAM and Maria ＆ Victorino scale had poor consistency （κw=0.156）. For the patients with acute DILI， RECAM， RUCAM， and Maria ＆ Victorino scales had a diagnostic inconsistency rate of 3.7%， 11.1%， and 42.6%， respectively； for the patients with hepatocellular type DILI， the three scales of a diagnostic inconsistency rate of 8.9%， 21.4%， and 62.5%， respectively； for the patients with cholestasis type or mixed type DILI， the three scales of a diagnostic inconsistency rate of 10.0%， 22.5%， and 47.5%， respectively. ConclusionThe use of RECAM and RUCAM scales in acute DILI can improve diagnostic rate， and for hepatocellular type DILI and DILI with the clinical manifestation of cholestasis （cholestasis type DILI and mixed type DILI）， the use of RECAM and RUCAM scales can also improve diagnostic rate. The selection of causality assessment scales with a relatively high accuracy based on the course and clinical classification of the disease may help to further improve clinical diagnostic rate.
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Drug-induced autoimmune-like hepatitis （DI-ALH） is a special clinical phenotype of drug-induced liver injury and has similar clinical features and laboratory test results to autoimmune hepatitis， and it is often difficult to distinguish them through liver biopsy. Therefore， correct differential diagnosis DI-ALH and autoimmune hepatitis is a crucial and difficult point in clinical practice. This article analyzes the research advances in the pathogenesis， clinical features， diagnosis and treatment， and prognosis of DI-ALH， in order to provide ideas for the diagnosis and treatment of such diseases among clinicians.
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Caveolin-1 （CAV1） is a structural protein of caveolae on the plasma membrane and is an important regulatory factor for liver function. CAV1 regulates hepatic lipid deposition， lipid and glucose metabolism， mitochondrial function， and hepatocyte proliferation through various molecular pathways. Therefore， CAV1 plays a crucial role in maintaining liver physiology during the metabolic regulatory processes such as hepatic steatosis and hepatocyte proliferation. Furthermore， CAV1 is also involved in the development and progression of different types of liver injury， hepatitis， and liver cirrhosis. This article reviews the role of CAV1 in liver-related diseases and its mechanism in the regulation of liver macrophages， so as to provide a theoretical basis for targeting CAV1 in the treatment of liver-related diseases.
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ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022 — 0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213 — 0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998 — 1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952 — 0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082 — 2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.
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Pharmacotherapy is the primary treatment method for hyperthyroidism. Antithyroid drugs can induce liver injury， and the diagnosis of drug-induced liver injury is mostly exclusive based on medical history collection， clinical symptoms， serum biochemistry， radiological examination， and histology. According to the severity of liver injury， drug-induced liver injury can be classified into mild， moderate， severe， and fatal degrees. Drug withdrawal may not be necessary for patients with mild liver injury， but regular monitoring of liver function is required； in severe cases， patients may develop liver failure， which may lead to a mortality rate， and early identification， timely drug withdrawal， and reasonable pharmacotherapy can help to avoid fatal consequences. The treatment principles of liver injury induced by antithyroid drugs include promoting the recovery of liver injury， preventing the severe exacerbation and chronicity of liver injury， and reducing the risk of death. Standardized medication， timely monitoring， early identification， and early treatment are important measures for the prevention and treatment of liver injury induced by antithyroid drugs.
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Polygonum multiflorum （PM）， a commonly used Chinese herbal medicine in clinical practice， has been associated with frequent reports of liver injury in recent years， and the medication safety of PM has attracted more and more attention in China and globally. This article reviews the recent research advances in the signaling pathways and mechanisms of PM in causing drug-induced liver injury （DILI） and aims to provide new ideas for the proper and rational use of PM in clinical practice. The results show that PM is involved in the regulation of various signaling pathways， and it leads to the death of hepatocytes by destroying mitochondrial function， exacerbating bile acid accumulation， and inducing immune response， oxidative stress， and endoplasmic reticulum stress， thereby inducing the development and progression of DILI through multiple targets， pathways， and levels.
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The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.
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Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.
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Drug-induced liver injury is caused by the drug itself and/or its metabolites during drug use or occurs due to hypersensitivity or reduced tolerance to the drug in a particular body type. In the last three years of the diagnosis and treatment of coronavirus disease 2019 （COVID-19）， antiviral drugs have played a very important role， but there are many reports on liver injury caused by anti-COVID-19 drugs in China and globally， with unknown pathogenesis of liver injury caused by such drugs. This article reviews the research advances in the types of antiviral drugs for COVID-19 and their mechanism in inducing liver injury， in order to promote the rational use of antiviral drugs.
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As an increasing number of emerging anti-tumor drugs are approved and marketed,the imperative for clinical safety monitoring and risk information management has grown significantly.Drug-induced neuropathy associated with these drugs exhibit characteristics such as insidious onset,rapid progression,and challenging treatment,ultimately leading to treatment failures.Therefore,a comprehensive understanding of the risk of neuropathy induced by emerging anti-tumor drugs,coupled with risk surveillance and early warning,as well as management and reporting,can significantly reduce the incidence and severity of drug-related diseases.This paper provides a review of the neuropathy caused by emerging anti-tumor drugs,introduces the pharmacovigilance system and risk information management measures in clinical usage,aiming to provide a reference for guiding the rational clinical use and minimizing the incidence of drug-induced diseases.
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Objective @#To establish an in vitro renal injury model of amikacin (AKN) and investigate the protective effect and mechanism of vaccarin (VA) in the AKN-induced in vitro renal injury model .@*Methods @#Human renal tubular epithelial cells (HK-2) were cultured in vitro and incubated with different drugs of AKN or/and VA to de- termine the optimal drug concentration based on cell viability tested by MTT. The changes in intracellular oxidative stress were assessed using the dihydroethidium ( DHE) probe and malondialdehyde ( MDA) /glutathione ( GSH) assay kits at different time points . Total RNA was extracted , and RT-qPCR was performed to detect the changes in the gene expression of kidney injury molecule-1 ( KIM-1) and neutropil gelatinase-associated lipocalin ( NGAL) . Western blot analysis was performed to detect the levels of ferroptosis-related markers solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in HK-2 cell lysis .@*Results @#High concentrations of AKN significantly decreased the viability of HK-2 cells in vitro , with a half maximal inhibitory concentration (IC50) of (5 . 74 ±0. 47) mmol/L. VA at concentrations of 25 - 100 μmol/L increased the viability of AKN-stimulated HK- 2 cells (P < 0. 05) . After treatment with AKN (4 mmol/L) , the mRNA expression levels of KIM-1 and NGAL were significantly higher than those of the negative control (NC) group ( P < 0. 001) . VA (50 μmol/L) significantly reduced the mRNA expression levels of KIM-1 (P < 0. 01) and NGAL (P < 0. 05) . The intensity of DHE staining increased after 3 hours of AKN treatment , but the difference was not statistically significant. However , the intensity of DHE staining was significantly higher in the 6 - 24 hours group compared to the 0 - hour group (P < 0. 01) . Furthermore , MDA levels significantly increased , while GSH levels significantly decreased after 6 - 24 hours of AKN treatment , with statistically significant differences (P < 0. 05) . After 6 - 24 hours of AKN stimula- tion , the ferroptosis-related proteins SLC7A11 and GPX4 both significantly decreased (P < 0. 001) . Co-incubation with VA for 24 hours effectively reversed the changes in DHE staining , MDA and GSH levels , as well as the chan- ges of SLC7A11 and GPX4 protein levels (P < 0. 001) .@*Conclusion @#In this study , an in vitro renal injury model was established by stimulating HK-2 cells with high concentrations of AKN , and it was found that VA might allevi- ate the damage to renal tubular cells caused by AKN via inhibiting oxidative stress related ferroptosis .
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@#Objective The potential mechanism of curcumin(CUR)combined with berberine(BBR)in improving drug-induced liver injury(DILI)was preliminarily predicted by a method of in vivo experiment in combination with network pharmacology.Methods The animal model was established by acetaminophen(APAP)-induced DILI and the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected in serum of mice.The network pharmacological approach was used to collect related targets of CUR,BBR,and DILI;Wayne mapping was carried out to screen intersection targets,followed by establishment of a protein-protein interaction(PPI)network of CUR-BBR-DILI.Functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were conducted finally.Results The in vivo experimental results showed that the combination of CUR and BBR can significantly reduce the serum ALT and AST levels in mice,which is better than administration alone;Network pharmacology experiment results exhibited that 291 related targets of CUR and 208 related targets of BBR were collected by PharmMapper database,and 904 related targets of DILI were collected by Genecards database;77 intersection targets were screened by Venny 2.1.0 database;52 gene functions and 20 signal pathways possibly in connection with the improvement of DILI via drug combination were obtained by GO and KEGG analysis,respectively;nine of the top ten core targets according to degree in PPI network were enriched to PI3K/AKT signaling pathway,which were in order as follows:SRC,EGFR,HSP90AA1,IGF1,HRAS,MAPK14,ESR1,CASP3,and PTK2.Conclusion DILI might be synergistically improved by CUR combined BBR through multi-target and multi-pathway manner,providing a theoretical basis for the elucidation of the mechanism of drug combination against DILI.
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ABSTRACT Objective: To report a pediatric case of drug-induced thrombotic microangiopathy caused by cocaine Case description: We report a nine-month-old patient who developed thrombotic microangiopathies after extreme cocaine intoxication, multiple organ dysfunction syndrome with hemodynamic dysfunction, anuric renal failure, liver failure, encephalopathy, and myocardial injury, corresponding phenotypically to thrombocytopenia-associated multiple organ failure. The patient received continuous venous hemofiltration and therapeutic plasma exchange, recovering satisfactorily. She was discharged after 30 days of hospitalization under the guidance of the childcare service, and was healthy after one year of follow-up. Toxicological samples confirmed high levels of cocaine and derivatives in blood, urine and hair. Comments: To our knowledge, this is the first reported pediatric case. There are particularities of cocaine intoxication pathophysiology that can trigger thrombotic microangiopathies because of vasoconstriction, direct endothelial injury, platelet activation, and increasing von Willebrand factor and fibrinogen levels. All of which results in a prothrombotic state, inflammatory dysregulation, and microvascular thrombi. The increasing use of cocaine, especially among young adults, puts children at high risk of toxicity, either by passive unintentional exposure, or abuse due to the increased availability in homes.
RESUMO Objetivo: Relatar um caso pediátrico de microangiopatia trombótica induzida por drogas causada por cocaína Descrição do caso: Relatamos uma paciente de nove meses de idade que desenvolveu microangiopatia trombótica após intoxicação extrema por cocaína, síndrome de disfunção de múltiplos órgãos com disfunção hemodinâmica, insuficiência renal anúrica, insuficiência hepática, encefalopatia e lesão miocárdica, correspondendo fenotipicamente à falência múltipla de órgãos associada à trombocitopenia. A paciente recebeu hemofiltração venosa contínua e plasmaférese terapêutica, recuperando-se satisfatoriamente. Recebeu alta após 30 dias de internação sob orientação do serviço de puericultura e estava saudável após um ano de seguimento. Amostras toxicológicas confirmaram altos níveis de cocaína e derivados no sangue, urina e cabelos. Comentários: Até onde sabemos, este é o primeiro caso pediátrico relatado. Existem particularidades da fisiopatologia da intoxicação por cocaína que podem desencadear a microangiopatia trombótica devido à vasoconstrição, lesão endotelial direta, ativação plaquetária e aumento do fator de von Willebrand e dos níveis de fibrinogênio. Tudo isso resulta em um estado pró-trombótico, desregulação inflamatória e trombos microvasculares. O uso crescente de cocaína, principalmente entre adultos jovens, coloca as crianças em alto risco de toxicidade, seja por exposição passiva não intencional ou abuso devido à maior disponibilidade nas residências.