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1.
HCA Healthc J Med ; 1(4): 201-204, 2020.
Article in English | MEDLINE | ID: mdl-37425664

ABSTRACT

Description Clenbuterol is a long-acting ß-agonist used in oral and inhaled form for asthma treatment outside the U.S. and in veterinary medicine within the U.S. It is also used off-label for anabolic effects worldwide. Toxicity with clenbuterol is increasingly seen in U.S. hospitals, primarily in younger individuals using the drug for competitive athletics or bodybuilding. We present a case of a young patient who presented after an intentional overdose and discuss the relevant literature. Presentations do not correlate with the dosage ingested. Signs and symptoms can range from simple nausea to myocardial ischemia, rhabdomyolysis and cardiogenic shock. Treatment of overdose is simple and should be promptly started using intravenous fluid hydration and potassium supplementation. Benzodiazepines may be utilized for agitation or delirium. ß-blockers or phenylephrine may be used to give hemodynamic support. More research is needed to gain an understanding of the optimal treatment of clenbuterol toxicity, especially if it becomes a more frequent reason for medical encounters in the U.S.

2.
J Virol ; 87(5): 2496-507, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23255787

ABSTRACT

Poly(ADP-ribose) polymerase 1 (PARP-1) is a cellular enzyme with a fundamental role in DNA repair and the regulation of chromatin structure, processes involved in the cellular response to retroviral DNA integration. However, the function of PARP-1 in retroviral DNA integration is controversial, probably due to the functional redundancy of the PARP family in mammalian cells. We evaluated the function of PARP-1 in retroviral infection using the chicken B lymphoblastoid cell line DT40. These cells lack significant PARP-1 functional redundancy and efficiently support the postentry early events of the mammalian-retrovirus replication cycle. We observed that DT40 PARP-1(-/-) cells were 9- and 6-fold more susceptible to infection by human immunodeficiency virus type 1 (HIV-1)- and murine leukemia virus (MLV)-derived viral vectors, respectively, than cells expressing PARP-1. Production of avian Rous-associated virus type 1 was also impaired by PARP-1. However, the susceptibilities of these cell lines to infection by the nonretrovirus vesicular stomatitis virus were indistinguishable. Real-time PCR analysis of the HIV-1 life cycle demonstrated that PARP-1 did not impair reverse transcription, nuclear import of the preintegration complex, or viral DNA integration, suggesting that PARP-1 regulates a postintegration step. In support of this hypothesis, pharmacological inhibition of the epigenetic mechanism of transcriptional silencing increased retroviral expression in PARP-1-expressing cells, suppressing the differences observed. Further analysis of the implicated molecular mechanism indicated that PARP-1-mediated retroviral silencing requires the C-terminal region, but not the enzymatic activity, of the protein. In sum, our data indicate a novel role of PARP-1 in the transcriptional repression of integrated retroviruses.


Subject(s)
Poly(ADP-ribose) Polymerases/metabolism , Retroviridae/genetics , Transcription, Genetic , Virus Replication/genetics , Animals , Avian Leukosis Virus/genetics , Avian Leukosis Virus/pathogenicity , Avian Leukosis Virus/physiology , Cell Line , Chickens , Gene Expression Regulation, Viral , Gene Knockout Techniques , HEK293 Cells , HIV-1/genetics , HIV-1/pathogenicity , HIV-1/physiology , Humans , Jurkat Cells , Leukemia Virus, Murine/genetics , Leukemia Virus, Murine/pathogenicity , Leukemia Virus, Murine/physiology , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases/genetics , Retroviridae/pathogenicity , Retroviridae/physiology , Vesicular stomatitis Indiana virus/genetics , Vesicular stomatitis Indiana virus/pathogenicity , Vesicular stomatitis Indiana virus/physiology , Virus Integration/genetics
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