ABSTRACT
PURPOSE: The aim of this study was to investigate the modulation of the expression status of 10 different genes involved in epigenetic regulation and apoptosis by the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza), as markers of response to treatment, in two different human malignant haematopoietic cell lines. METHODS: In our analysis we used the SybrGreen technology and gene-specific primers for the qRT-PCR analysis of 10 genes, in cDNA of PC-MDS and K562 cell lines, treated by 1 micromole of 5-Aza for 24h. RESULTS: DNMT1 and DNMT3A showed statistically significant decrease of expression in 5-Aza-treated PC-MDS cells, whereas DNMT3B showed significantly decreased expression in 5-Aza-treated K562 cells. The members of the Bcl- 2 family of apoptosis-regulating genes Bcl-2 and Bax showed statistically significant differences in expression, in comparison with non-treated PC-MDS cells. Our most interesting result was the significant upregulation (re-expression) of p15, in 5-Aza-treated PC-MDS cells. CONCLUSION: The re-expression of p15 in PC-MDS cell line evaluated by qRT-PCR makes this novel cell line a suitable model for the studies of pharmacologic demethylation as a plausible mechanism resulting in hematologic response in myelodysplastic syndrome (MDS).
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Apoptosis , Azacitidine/pharmacology , Epigenesis, Genetic , Myelodysplastic Syndromes/drug therapy , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methyltransferase 3A , Gene Expression Regulation, Neoplastic , Humans , K562 Cells , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/pathology , Oxidative Stress , RNA, Messenger/analysisABSTRACT
Inflammatory bowel disease (IBD) encompasses ulcerative colitis and Crohn's disease. Since the etiology of both diseases, is undetermined the causal therapy do not exist. Medical treatment has focused on nonspecific suppressions of the inflammatory process. There are four groups of IBD drugs: anti-inflammatory medicaments, immunomodulators, antidiarrheal agents, and biologic therapy. In a last year immunosuppressives become the very essential IBD drugs. Azathioprine is drug of choice for chronically active Crohn's disease; methotrexate become the second line immunosuppressive drug. It appears that anti-TNG monoclonal antibodies, cA2 (infliximab) may produce rapid control of active Crohn's disease and achieve tissue healing. Topically acting glucocorticosteroids are a safer than standard glicocorticosteroids in ileocolonic Crohn's disease. Cyclosporin is becoming a drug of choice in severely active ulcerative colitis. Anti-inflammatory agents, sulfasalazine and 5-ASA drugs are recommended in treatment mild and moderately active IBD and as maintenance treatment in ulcerative colitis. Corticosteroids still have the main role in the treatment of active IBD. There is no convincing data for efficacy of corticosteroids as maintenance therapy.
Subject(s)
Inflammatory Bowel Diseases/drug therapy , HumansABSTRACT
A 23-year old male patient had eight distinct episodes of hemolytic uremic syndrome (HUS) between 8.5 and 15 years of age, five of them accompanied by hypocomplementemia. In the further course, severe hypertension, renal insufficiency as well as protein-losing enteropathy due to intestinal lymphangiectasia developed, whilst hypocomplementemia persisted. The association of recurrent HUS with hypocomplementemia and intestinal lymphangiectasia may represent a new association within a subgroup of the atypical HUS.
Subject(s)
Complement System Proteins/deficiency , Hemolytic-Uremic Syndrome/pathology , Lymphangiectasis, Intestinal/pathology , Adult , Hemolytic-Uremic Syndrome/complications , Humans , Hypertension/etiology , Hypertension/physiopathology , Jejunum/pathology , Kidney/pathology , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/physiopathology , Lymphangiectasis, Intestinal/complications , Male , Protein-Losing Enteropathies/etiology , Protein-Losing Enteropathies/physiopathology , RecurrenceABSTRACT
The authors report a case of sarcoidosis associated with protein losing enteropathy. The diagnosis of intrathoracic stage I sarcoidosis was based on x-ray and biopsy of mediastinal lymph nodes. Enteric protein loss was suspected because of edema lasting for 2 yr, hypoproteinemia, decreased concentrations of serum immunoglobulins, and lymphopenia involving mainly T-cells and proved by 51CrCl3 test (21%/120 hr). Lymphography was consistent with granulomatous involvement of retroperitoneal lymph glands while small bowel biopsy showed blunt villi and dilated lacteals. All the pathological parameters normalized after 6 mo of prednisone treatment. In some cases of sarcoidosis, when abdominal lymph glands are involved, cellular and humoral immunologic derangements may be caused or potentiated by excessive enteric protein and lymphocyte loss.
