Tuberculosis Arthritis Genu Sinistra with Drug-Induced Liver Injury, COVID 19 Confirmed

Background. Tuberculosis is still a significant health problem, especially in developing countries. Although pulmonary tuberculosis is the most common form of the disease, extrapulmonary tuberculosis also contributes significantly to morbidity and mortality. 10-15% of extrapulmonary cases are due to tuberculous arthritis. The following is a case report of a 36-year-old woman with a diagnosis of genu Sinistra tuberculosis arthritis and drug-induced hepatotoxic injury due to OAT. Case presentation. A woman, 36 years old, Muslim, addresses Banyuasin. The patient is a housewife, treated at Dr. Moh Hoesin General Hospital since October 11, 2021. The main complaint in the form of pain in the left knee has been getting worse since 1 week before being admitted to the hospital. 4 months before admission the hospital, the patient complained of left knee pain, the pain felt like being stabbed, coming and going, especially when walking. In this patient, there was a complaint of nausea that was felt in the pit of the stomach. The results of laboratory examinations showed an increase in the transaminase enzyme and hyperuricemia, so it was suspected that the patient had DILI due to OAT drugs. Hepatocyte death in DILI can occur through two processes, namely processes mediated by apoptosis or necrosis. In apoptosis, cell shrinkage and fragmentation occur into small pieces with the cell membrane intact. These fragments are cleared by phagocytosis and generally do not stimulate the host immune response. Conclusion. A patient diagnosed with arthritis tuberculosis genu Sinistra with Drug-Induced Liver Injury and Confirmed COVID 19.

Puromycin-based purification of cells with high expression of the cytochrome P450 CYP3A4 gene from a patient with drug-induced liver injury (DILI)

Background Many drugs have the potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in hepatocytes. Hepatocytes can be accurately evaluated for drug-mediated CYP3A4 induction; this is the gold standard for in vitro hepatic toxicology testing. However, the variation from lot to lot is an issue that needs to be addressed. Only a limited number of immortalized hepatocyte cell lines have been reported. In this study, immortalized cells expressing CYP3A4 were generated from a patient with drug-induced liver injury (DILI). Methods To generate DILI-derived cells with high expression of CYP3A4, a three-step approach was employed: (1) Differentiation of DILI-induced pluripotent stem cells (DILI-iPSCs); (2) Immortalization of the differentiated cells; (3) Selection of the cells by puromycin. It was hypothesized that cells with high cytochrome P450 gene expression would be able to survive exposure to cytotoxic antibiotics because of their increased drug-metabolizing activity. Puromycin, a cytotoxic antibiotic, was used in this study because of its rapid cytocidal effect at low concentrations. Results The hepatocyte-like cells differentiated from DILI-iPSCs were purified by exposure to puromycin. The puromycin-selected cells (HepaSM or SI cells) constitutively expressed the CYP3A4 gene at extremely high levels and exhibited hepatocytic features over time. However, unlike primary hepatocytes, the established cells did not produce bile or accumulate glycogen. Conclusions iPSC-derived hepatocyte-like cells with intrinsic drug-metabolizing enzymes can be purified from non-hepatocytes and undifferentiated iPSCs using the cytocidal antibiotic puromycin. The puromycin-selected hepatocyte-like cells exhibited characteristics of hepatocytes after immortalization and may serve as another useful source for in vitro hepatotoxicity testing of low molecular weight drugs.

BML-257, a small molecule that protects against drug induced liver injury in zebrafish

The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug induced liver injury (DILI) would be valuable in such situations. We used hepatocyte-specific expression of bacterial nitroreductase in zebrafish to cause temporally controlled liver damage. This transgenic line was used to run a whole organism based chemical screen in zebrafish larvae. In this screen we identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 also showed remarkable protective action in two independent toxicological models of liver injury caused by acetaminophen and Isoniazid. This suggests that BML-257 may have the potential to protect against multiple kinds of drug induced liver injury.

The Role of Peroxiredoxins in the Regulation of Sepsis

Oxidative stress, a result of a disturbance in redox homeostasis, is considered to be one of the main aggravating events in the pathogenesis of immune disorders. Peroxiredoxins (Prdxs) are an enzyme family that catalyzes the reduction of peroxides, including hydrogen peroxide, lipid peroxides, and nitrogen peroxides. Although the maintenance of cellular redox homeostasis through Prdxs is essential for surviving in adverse environments, Prdxs also participate in the regulation of cellular signal transduction by modulating the activities of a panel of molecules involved in the signal transduction process. Although Prdxs were discovered as intracellular anti-oxidative enzymes, recent research has revealed that Prdxs also play important roles in the extracellular milieu. Indeed, Prdxs have been shown to have the capacity to activate immune cells through ligation with innate immune receptors such as toll-like receptors (TLRs). In this review, we will summarize the intracellular as well as extracellular roles of Prdxs for and against the pathogenesis of inflammatory disorders including sepsis, hemorrhagic shock, and drug-induced liver injury.

Pharmacotherapies for Drug-Induced Liver Injury: A Current Literature Review

Drug-induced liver injury (DILI) has become a serious public health problem. For the management of DILI, discontinuation of suspicious drug or medicine is the first step, but the treatments including drugs and supporting approaches are needed. Reference to clinical patterns and disease severity grades of DILI, the treatment drugs were considered to summarize into hepatoprotective drugs (N-acetylcysteine and Glutathione, Glycyrrhizin acid preparation, Polyene phosphatidylcholine, Bicyclol, Silymarin), anticholestatic drug (Ursodeoxycholic acid, S-adenosylmethionine, Cholestyramine), immunosuppressants (Glucocorticoids) and specific treatment agents (L-carnitine, Anticoagulants). The current article reviewed the accumulated literature with evidence-based medicine researches for DILI in clinical practice. Also the drawbacks of the clinical studies involved in the article, unmet needs and prospective development for DILI therapy were discussed.