Interleukin-18 (IL-18) elicited a robust hypertrophy response in H9c2 cardiomyocytes as judged by their accelerated rates of protein synthesis and increased cell size. Evidently, IL-18 treatment also induced a cardiac hypertrophy-specific program of gene expression in H9c2 cardiomyocytes since they elicited enhanced expression of atrial naturetic factor (ANF), desmin, and skeletal alpha-actin genes accompanied by a canonical switch in the transcription of alpha- and beta-myosin heavy chain (MyHC) genes. Co-treatment of H9c2 cells with m-carboxycinnamic acid bis-hydroxamide (CBHA), an inhibitor of histone deacetylases, significantly blocked both morphological and molecular manifestations of IL-18-induced cardiac hypertrophy in vitro. IL-18 treatment led to activation of phosphoinositide-3-kinase and phosphorylated Akt/protein kinase B, while CBHA blunted this pathway via inducing the expression of its upstream regulator, PTEN (phosphatase and tensin homolog). The architecture of bulk chromatin of H9c2 cells exposed to IL-18 and/or CBHA was significantly altered as judged by the extent of covalent modifications of its constituent histones. The chromatin immuno-precipitation (ChIP) assays revealed that IL-18-induced specific epigenetic changes in the chromatin of ANF, desmin, skeletal alpha-actin, and MyHC genes that were largely neutralized by CBHA. We demonstrate for the first time that 'histone code' of the entire approximately 50 kb genomic DNA encoding the alpha- and beta-MyHC genes and the intergenic DNA that generates anti-beta-MyHC RNA was uniquely modulated by pro- and anti-hypertrophy signals of IL-18 and CBHA, respectively.
Herbal medicines have been used for the treatment of various ailments since time immemorial. Black cohosh (BC) is well known for the treatment of postmenopausal symptoms, with conflicting evidence supporting its safety and benefits. We present a rare case of BC-induced autoimmune hepatitis (AIH) with hepatotoxicity in a 69-year-old female. To our knowledge, this represents the third case of BC-induced AIH.
Pain in abdomen has wide differentials and narrowing down the clinical possibilities depends on type of pain, location, characterization which is usually assisted by imaging studies. Cholecystitis and cholelithiasis are amongst the common causes of acute abdomen. This study reviews the literature for the clinical characteristics, differential diagnosis, treatment and prognosis of reported cases of gallbladder myeloid sarcoma (GB-MS) who presented with abdominal symptoms. A total of 17 cases of GB-MS were studied. The median age was 52 years with age range of 23 to 84 years. All except 1 patient presented with abdominal symptoms. Based on imaging or pathological studies, 3 cases were initially confused with gallbladder lymphoma or cancer. Only 5 patients were treated with AML like chemotherapy. Treatmentgiven included combinations of surgery, chemotherapy, and radiotherapy. None of the cases underwent HSCT for GB-MS. Seven patients were alive till the time of last F/U, 9 succumbed to death while F/U of 1 patient was not available. Irrespective of treatment protocol followed suggesting the poor prognosis in GB-MS cases. In conclusion, acute abdomen complicating blood malignancies is life threatening and can be devastating if not detected and treated in a timely fashion.
The incidence of amoxicillin/clavulanate (Augmentin) induced liver injury is relatively low when compared to other medications. Amoxicillin/clavulanic acid is one of the most frequently prescribed antibiotics by physicians and is used to treat various bacterial infections. However, amoxicillin/clavulanate can cause severe side effects, usually gastrointestinal like nausea and vomiting, rash, and sometimes hematologic like thrombocytopenia. Here, we present a case report where a 63-year-old male treated for a dog bite with amoxicillin/clavulanate acid four weeks ago presents to the hospital with severe cholestatic hepatitis, nausea, and pruritis.
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