Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane transport of antisense oligonucleotides (ODN) is an inefficient process which requires special carriers for their intracellular delivery. We have developed a delivery system for AS-ODN and their phosphorothioate analogues (AS-PTO) directed against human immunodeficiency virus type 1 (HIV-1) tat mRNA for efficient transfection of HIV-1 target cells. Protamine was used to complex AS-ODN and AS-PTO to form nanoparticles with diameters of about 180 nm and surface charges in the range of -18 to +30 mV. Cellular uptake of these nanoparticles was significantly enhanced compared to naked oligonucleotides. A double labeling technique with fluorescently tagged protamine and AS-ODN was used to follow the intracellular fate of the nanoparticles. Protamine/AS-ODN nanoparticles showed release of the antisense compound leading to specific inhibition of tat mediated HIV-1 transactivation. In contrast, protamine/AS-PTO complexes were stable over 72 h, and failed to release AS-PTO. These results demonstrate that protamine/AS-ODN nanoparticles are useful for future therapeutical application to inhibit viral gene expression.
 ...
PMID:Intracellular tracking of protamine/antisense oligonucleotide nanoparticles and their inhibitory effect on HIV-1 transactivation. 1512 Sep 5

BACKGROUND: Misuse of prescription-type opioids and related adverse health effects are increasing, but little is known about the role of these drugs as a precursor to heroin use. We conducted an exploratory study to determine the proportion of young heroin injectors reporting problematic use of prescription-type opioids prior to using heroin, and to describe the factors associated with prior problematic prescription-type opioid use. METHODS: Between March 2009 and June 2010, we recruited injection drug users (IDUs) for a cross-sectional study of hepatitis C virus infection risk. Participants were aged 18-40 years and had injected illicit drugs within the previous six months. A computerized self-administered survey assessed sociodemographics, drug use history, human immunodeficiency virus (HIV)/hepatitis C virus risk behaviors and perceptions, and medical history. We added questions on prescription-type opioid use to the parent study in March 2010; heroin injectors who subsequently enrolled and reported problematic prescription-type opioid use prior to heroin initiation were compared with other heroin IDUs using univariate and multivariate regression methods. RESULTS: Among 123 heroin IDUs, 49 (39.8%) reported problematic prescription-type opioid use prior to heroin initiation ("prescription-type opioid first injection drug users" [PTO-First IDUs]). PTO-First IDUs had higher odds of injecting with friends (adjusted odds ratio [AOR] 6.01; 95% confidence interval [CI] 1.90-19.07), getting new syringes from a spouse/family member/sex partner (AOR 23.0; 95% CI 2.33-226.0), knowing about the local syringe exchange program (AOR 7.28; 95% CI 1.17-45.05), using powder cocaine (AOR 3.75; 95% CI 1.43-9.86), and perceiving themselves as less likely than other IDUs to get HIV (AOR 4.32; 95% CI 1.26-14.77). They had lower odds of ever being tested for HIV (AOR 0.25; 95% CI 0.08-0.80). CONCLUSION: A high proportion of young heroin IDUs reported problematic prescription-type opioid use prior to initiating heroin use. Our study provides several avenues for future investigation to help further characterize this subset of IDUs and their risks and perceptions related to HIV and other blood-borne pathogens.
 ...
PMID:Problematic use of prescription-type opioids prior to heroin use among young heroin injectors. 2329 47