Chemicals and Drugs Commons^™

Prescription Drug Diversion: Predictors Of Illicit Acquisition And Redistribution In Three U.S. Metropolitan Areas, Shana Harris, Valentina Nikulina, Camila Gelpi-Acosta, Cory Morton, Valerie Newsome, Alana Gunn, Heidi Hoefinger, Ross Aikins, Vivian Smith, Victoria Barry, Martin J. Downing Jr.

Publications and Research

Objective: Prescription drug diversion, the transfer of prescription drugs from lawful to unlawful channels for distribution or use, is a problem in the United States. Despite the pervasiveness of diversion, there are gaps in the literature regarding characteristics of individuals who participate in the illicit trade of prescription drugs. This study examines a range of predictors (e.g., demographics, prescription insurance coverage, perceived risk associated with prescription drug diversion) of membership in three distinct diverter groups: individuals who illicitly acquire prescription drugs, those who redistribute them, and those who engage in both behaviors.

Methods: Data were drawn from a cross-sectional Internet …

Sample Limited Characterization Of A Novel Disulfide- Rich Venom Peptide Toxin From Terebrid Marine Snail Terebra Variegata, Prachi Anand, Alexandre Grigoryan, Mohammed H. Bhuiyan, Beatrix Ueberheide, Victoria Russell, Jose Quiñonez, Patrick Moy, Brian T. Chait, Sébastien F. Poget, Mandë Holford

Publications and Research

Disulfide-rich peptide toxins found in the secretions of venomous organisms such as snakes, spiders, scorpions, leeches, and marine snails are highly efficient and effective tools for novel therapeutic drug development. Venom peptide toxins have been used extensively to characterize ion channels in the nervous system and platelet aggregation in haemostatic systems. A significant hurdle in characterizing disulfide-rich peptide toxins from venomous animals is obtaining significant quantities needed for sequence and structural analyses. Presented here is a strategy for the structural characterization of venom peptide toxins from sample limited (4 ng) specimens via direct mass spectrometry sequencing, chemical synthesis and NMR …

Reductions In Serum Igf-1 During Aging Impair Health Span, Zhenwei Gong, Oran Kennedy, Hui Sun, Yingjie Wu, Garry A. Williams, Laura Klein, Luis Cardoso, Ronald W. Matheny Jr, Gene B. Hubbard, Yuji Ikeno, Roger P. Farrar, Mitchell B. Schaffler, Martin L. Adamo, Radhika H. Muzumdar, Shoshana Yakar

Publications and Research

In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF- 1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging. Thus, animal models with congenital disruption of the GH/ IGF-1 axis are unable …

Testosterone, Cardiovascular, Men, Trial, Lin Xu, Guy Freeman, Benjamin J. Cowling, Mary Schooling

Publications and Research

Background
Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease.

Methods
A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, …

The Effect Of Statins On Testosterone In Men And Women, A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Mary Schooling, Shiu Lun Au Yeung, Guy Freeman, Benjamin J. Cowling

Publications and Research

Background
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates morethan other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statinsunexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would beexpected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.

Methods
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, …

Circularized Synthetic Oligodeoxynucleotides Serve As Promoterless Rna Polymerase Iii Templates For Small Rna Generation In Human Cells, Christine I. Seidl, Lodoe Lama, Kevin Ryan

Publications and Research

Synthetic RNA formulations and viral vectors are the two main approaches for delivering small therapeutic RNA to human cells. Here we report findings supporting an alternative strategy in which an endogenous human RNA polymerase (RNAP) is harnessed to make RNA hairpin-containing small RNA from synthetic single-stranded DNA oligonucleotides. We report that circularizing a DNA template strand encoding a pre-microRNA hairpin mimic can trigger its circumtranscription by human RNAP III in vitro and in human cells. Sequence and secondary structure preferences that appear to promote productive transcription are described. The circular topology of the template is required for productive transcription, at …

Ambiguity, Ambivalence, And Apprehensions Of Taking Hiv-1 Pre-Exposure Prophylaxis Among Male Couples In San Francisco: A Mixed Methods Study, Parya Saberi, Kristine Elizabeth Gamarel, Torsten B. Neilands, Megan Comfort, Nicolas Sheon, Lynae A. Darbes, Mallory O. Johnson

Publications and Research

Objective: We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIVpositive) male couples’ PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple.

Design: Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants’ awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level …

Under The Gun: Ongoing Assaults On Bahrain’S Health System, Richard Sollom, Holly G. Atkinson

Publications and Research

In February 2011, the Government of Bahrain began targeting health professionals who treated protesters. In April 2012, PHR's Richard Sollom, Deputy Director, and Holly Atkinson, MD, FACP, past President of PHR's Board and volunteer expert, authored a report showing the devastation on Bahrain's health system that have resulted from the Government of Bahrain’s continued assault on doctors, patients, and the healthcare system.

Solution Structure And Dna-Binding Properties Of The Phosphoesterase Domain Of Dna Ligase D, Aswin Natarajan, Kaushik Dutta, Deniz B. Temel, Pravin A. Nair, Stewart Shuman, Ranajeet Ghose

Publications and Research

The phosphoesterase (PE) domain of the bacterial DNA repair enzyme LigD possesses distinctive manganese-dependent 3'-phosphomonoesterase and 3'-phosphodiesterase activities. PE exemplifies a new family of DNA end-healing enzymes found in all phylogenetic domains. Here, we determined the structure of the PE domain of Pseudomonas aeruginosa LigD (PaePE) using solution NMR methodology. PaePE has a disordered N-terminus and a well-folded core that differs in instructive ways from the crystal structure of a PaePE•Mn(2+)• sulfate complex, especially at the active site that is found to be conformationally dynamic. Chemical shift perturbations in the presence of primertemplate duplexes with 30-deoxynucleotide, …

Trends In The Clinical Characteristics Of Hiv Infected Patients Initiating Antiretroviral Therapy In Kenya, Uganda And Tanzania Between 2002 And 2009, Elvin H. Geng, Peter W. Hunt, Lameck O. Diero, Sylvester Kimaiyo, Geofrey R. Somi, Pius Okong, David R. Bangsberg, Mwebesa B. Bwana, Craig R. Cohen, Juliana A. Otieno, Deo Wabwire, Batya Elul, Denis Nash, Philippa J. Easterbrook, Paula Braitstein, Beverly S. Musick, Jeffrey N. Martin, Constantin T. Yiannoutsos, Kara Wools-Kaloustian

Publications and Research

Background: East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIVinfected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described.

Methods: We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation …

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

Publications and Research

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …

A Quantitative Synthesis Of The Medicinal Ethnobotany Of The Malinké Of Mali And The Asháninka Of Peru, With A New Theoretical Framework, Nathaniel Bletter

Publications and Research

Background: Although ethnomedically and taxonomically guided searches for new medicinal plants can improve the percentage of plants found containing active compounds when compared to random sampling, ethnobotany has fulfilled little of its promise in the last few decades to deliver a bounty of new, laboratory-proven medicinal plants and compounds. It is quite difficult to test, isolate, and elucidate the structure and mechanism of compounds from the plethora of new medicinal plant uses described each year with limited laboratory time and resources and the high cost of clinical trials of new drug candidates.

Methods: A new quantitative theoretical framework of mathematical …