ABSTRACT
Diagnosis and treatment of myocarditis can be challenging, including determining indications for heart transplantation. We present a 6-year medical history of a 54 years old patient with severe morphologically verified viral-negative lymphocytic myocarditis and systemic manifestations (onset of hemorrhagic vasculitis) combined with moderate coronary atherosclerosis, which regressed according to repeated coronary angiography. For 5 years, the patient received immunosuppressive therapy with methylprednisolone and azathioprine with a significant improvement. Repeated relapses of atrial fibrillation required correction of basic therapy and plasmapheresis. The disease was complicated by thyrotoxicosis and multi-organ dysfunction; the autopsy showed persistent myocarditis activity. The myocarditis is a chronic condition and requires a review of the treatment strategy at each stage.
Subject(s)
Myocarditis , Virus Diseases , Humans , Middle Aged , Myocarditis/diagnosis , Myocarditis/etiology , Myocarditis/therapy , Myocardium , Immunosuppressive Agents/therapeutic use , Biopsy , AzathioprineABSTRACT
Proteins of the NUDIX hydrolase (NUDT) superfamily that cleave organic pyrophosphates are found in all classes of organisms, from archaea and bacteria to higher eukaryotes. In mammals, NUDTs exhibit a wide range of functions and are characterized by different substrate specificity and intracellular localization. They control the concentration of various metabolites in the cell, including key regulatory molecules such as nicotinamide adenine dinucleotide (NAD), ADP-ribose, and their derivatives. In this review, we discuss the role of NUDT proteins in the metabolism of NAD and ADP-ribose in human and animal cells.
Subject(s)
Adenosine Diphosphate Ribose/metabolism , Mammals/metabolism , NAD/metabolism , Pyrophosphatases/metabolism , Adenosine Diphosphate Ribose/chemistry , Animals , Escherichia coli/metabolism , Humans , Intracellular Space/metabolism , NAD/chemistry , Oxidation-Reduction , Pyrophosphatases/chemistry , Pyrophosphatases/genetics , Saccharomyces cerevisiae/metabolism , Substrate Specificity , Nudix HydrolasesABSTRACT
Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form NADP are the major coenzymes in the redox reactions of various essential metabolic pathways. NAD+ also serves as a substrate for several families of regulatory proteins, such as protein deacetylases (sirtuins), ADP-ribosyltransferases, and poly(ADP-ribose) polymerases, that control vital cell processes including gene expression, DNA repair, apoptosis, mitochondrial biogenesis, unfolded protein response, and many others. NAD+ is also a precursor for calcium-mobilizing secondary messengers. Proper regulation of these NAD-dependent metabolic and signaling pathways depends on how efficiently cells can maintain their NAD levels. Generally, mammalian cells regulate their NAD supply through biosynthesis from the precursors delivered with the diet: nicotinamide and nicotinic acid (vitamin B3), as well as nicotinamide riboside and nicotinic acid riboside. Administration of NAD precursors has been demonstrated to restore NAD levels in tissues (i.e., to produce beneficial therapeutic effects) in preclinical models of various diseases, such as neurodegenerative disorders, obesity, diabetes, and metabolic syndrome.
Subject(s)
Cells/metabolism , NAD/metabolism , Animals , Cells/drug effects , Humans , Molecular Targeted Therapy , NAD/biosynthesisABSTRACT
A new class of small RNP (alpha-RNP) has been detected and identified in nuclei and cytoplasm of A-562 erythroid leukemia cell line; these RNPs have a characteristic spectrum of proteins containing conservative and specific components and a special RNA component, which contains a small antisense component (alpha-RNA), a homolog of short dispersed Alu repeats. alpha-RNP is highly stable, tightly associated with chromatin in the nucleus, and is found in the free state in cytoplasm. The composition of nuclear and cytoplasmic alpha-RNP differ and have a specific pattern of changes in response to dimethylsulfoxide, an agent causing differentiation.
Subject(s)
Erythroid Precursor Cells/cytology , RNA, Antisense/genetics , RNA, Neoplasm/genetics , Ribonucleoproteins, Small Nuclear/genetics , Cell Differentiation/drug effects , Cell Nucleus/chemistry , Cell Nucleus/drug effects , Cytoplasm/chemistry , Cytoplasm/drug effects , Dimethyl Sulfoxide/pharmacology , Erythroid Precursor Cells/chemistry , Erythroid Precursor Cells/drug effects , Humans , Leukemia, Erythroblastic, Acute/genetics , RNA, Antisense/analysis , RNA, Antisense/drug effects , RNA, Neoplasm/analysis , RNA, Neoplasm/drug effects , Ribonucleoproteins, Small Nuclear/analysis , Ribonucleoproteins, Small Nuclear/drug effects , Tumor Cells, CulturedABSTRACT
The symptoms and the course of herpes zoster are analyzed in 85 children aged 5 months to 15 years. Many systems of the body were shown to be involved in the process of the disease which is characteristic of neuroviral infections. The authors postulate the etiologic unity of chicken pox and herpes zoster as two clinical forms of the same epidemic process. The questions of treatment are outlined.