Medicine and Health Sciences Commons^™

The Role Of P2x Receptors In Hiv And Opiate-Related Neurotoxicity, Mary Sorrell

Theses and Dissertations

Emerging evidence suggests that opioid drugs can exacerbate neuroAIDS. Microglia are the principal neuroimmune effectors thought to be responsible for neuron damage in HIV-infected individuals, and evidence suggests that drugs acting via opioid receptors in microglia aggravate the neuropathophysiological effects of HIV. The P2X family of ATP activated ligand-gated ion channels regulates key aspects of microglial function. In addition, opioid-dependent microglial activation has been reported to be mediated through P2X4 signaling, prompting us to investigate P2X receptors contribution to the neurotoxic effects of HIV and morphine. In vitro experiments showed treatment with TNP-ATP prevented the neurotoxic effects of morphine and/or …

Cocaine Enhances Hiv-1 Infectivity In Monocyte Derived Dendritic Cells By Suppressing Microrna-155, Jessica Napuri, Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Marisela Agudelo, Adriana Yndart-Arias, Madhavan Nair, Shailendra K. Saxena

HWCOM Faculty Publications

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and …

Targeted Brain Derived Neurotropic Factors (Bdnf) Delivery Across The Blood-Brain Barrier For Neuro-Protection Using Magnetic Nano Carriers: An In-Vitro Study, Sudheesh Pilakka-Kanthikeel, Venkata Subba Rao Atluri, Vidya Sagar, Shailendra K. Saxena, Madhavan Nair

HWCOM Faculty Publications

Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; …

Human Synaptic Plasticity Gene Expression Profile And Dendritic Spine Density Changes In Hiv-Infected Human Cns Cells: Role In Hiv-Associated Neurocognitive Disorders (Hand), Venakata Subba Rao Alturi, Sudheesh P. Kanthikeel, Pichili V.B. Reddy, Adriana Yndart, Madhavan P.N. Nair

HWCOM Faculty Publications

HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated …

Investigation Of The Frequency Of The Mutant Ccr5-Δ32 Allele Related To Hiv Resistance In Turkey, Gamze Karakaya, Fatma Azi̇ze Budak Yildiran, Şükran Çakir Arica

Turkish Journal of Medical Sciences

To determine the frequency with which the CCR5-\Delta32 mutant allele caused resistance to HIV, which is main agent of AIDS in all geographic regions of Turkey. Materials and methods: Randomly selected human blood samples from 400 healthy individuals were collected. The polymerase chain reaction method was used to determine the CCR5-\Delta32 polymorphism and samples were screened using 2 primers. Results: The frequency of wild alleles was found to be 0.9738 and the frequency of mutant alleles was found to be 0.0262. The highest frequency of the CCR5-\Delta32 allele was found to be 0.0726 in the Central Anatolia region. The lowest …

Living With Uncertainty: Acting In The Best Interests Of Women, Erica Gollub, Zena Stein

HWCOM Faculty Publications

A recent multi-country study on hormonal contraceptives (HC) and HIV acquisition and transmission among African HIV-serodiscordant couples reported a statistically significant doubling of risk for HIV acquisition among women as well as transmission from women to men for injectable contraceptives. Together with a prior cohort study on African women seeking health services, these data are the strongest yet to appear on the HC-HIV risk. This paper will briefly review the Heffron study strengths and relevant biological and epidemiologic evidence; address the futility of further trials; and propose instead an alternative framework for next steps. The weight of the evidence calls …

Relationships And Context As A Means For Improving Disease Prevention And Sexual Health Messages, Lisa D. Lieberman

Department of Public Health Scholarship and Creative Works

In many ways, the HIV epidemic changed the discourse about sex in the United States and worldwide (Ehrhardt, 1992; Everett, 1986) and continues to drive approaches to sex education. After a period of rapid growth in the late 1980s (approximately 150,000 new infections per year), by the late 1990s, HIV rates in the United States slowed to some 40,000 new infections annually (Centers for Disease Control and Prevention [CDC], 2001), and new HIV infections continue to hover around that number. The first successful examples of behavior change that resulted in decreased HIV transmission emerged from …

Functional Recovery Of Untreated Human Immunodeficiency Virus-Associated Guillain-Barré Syndrome: A Case Report, Adam L. Schreiber, John W. Norbury Iii, Eduardo A. De Sousa

Department of Rehabilitation Medicine Faculty Papers

HIV-associated Guillain-Barré Syndrome is a well-documented phenomenon, typically occurring at seroconversion. GBS may result in functional impairment treated with a combination of medications, plasmapheresis, and rehabilitation. The quantified functional recovery of HIV-associated GBS with or without HIV treatment is not well-described. Utilizing serial FIM scoring, we describe a patient’s recovery from HIV-associated GBS after treatment with IVIg and acute inpatient rehabilitation without HIV treatment.

Comparative Gender Analysis Of The Efficacy And Safety Of Atazanavir/Ritonavir And Lopinavir/Ritonavir At 96 Weeks In The Castle Study., Kathleen E Squires, Margaret Johnson, Rong Yang, Jonathan Uy, Louise Sheppard, Judith Absalon, Donnie Mcgrath

Department of Medicine Faculty Papers

OBJECTIVES: To examine whether the overall results of the CASTLE study pertain to both genders, we analysed the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir in 277 female and 606 male patients in the open-label, multinational trial over 96 weeks. The trial is registered with ClinicalTrials.gov, number NCT00272779.

METHODS: Treatment-naive patients aged ≥ 18 years with HIV-1 RNA ≥ 5000 copies/mL were randomized to receive either atazanavir/ritonavir 300/100 mg once daily or lopinavir/ritonavir 400/100 mg twice daily, with fixed-dose tenofovir/emtricitabine 300/200 mg once daily.

RESULTS: At week 96, confirmed virological response rates (HIV RNA <50 copies>/mL; intent-to-treat analysis) were higher in …

Preventing Mother-To-Child Transmission Of Human Immunodeficiency Virus-1 (Hiv-1): Effects Of Intrapartum And Neonatal Single-Dose Nevirapine Prophylaxis And Subsequent Hiv-1 Drug Resistance At Antiretroviral Treatment Initiation, Amanda L. Harmon

CMC Senior Theses

The prevention of mother-to-child transmission is one of the most powerful tools in human immunodeficiency virus type 1 (HIV-1) prevention and has huge potential to improve both maternal and child health. In the absence of any preventative measures, infants born to and breastfed by their HIV-positive mothers have roughly a one-in-three chance of acquiring the infection themselves. HIV can be passed on from mother-to-child during pregnancy, during labor and delivery, and even after during breastfeeding.

Intrapartum and neonatal single-dose nevirapine (sd-NVP) is the foundation of preventing mother-to-child transmission in lower resource settings where it has been used alone or as …

Killer Immunoglobulin-Like Receptors And Human Leukocyte Polymorphisms In Hiv-1 Pathogenesis, Aimee Marie Merino

All ETDs from UAB

Human leukocyte antigen (HLA) molecules influence the adaptive and innate immune responses through interactions with cytotoxic T lymphocytes and natural killer cells (NK). HLA influence the activation state of NK through direct binding to killer immunoglobulin-like receptors (KIR) and presentation of HLA-derived peptides to NKG2 receptors. Activated NK can kill HIV-infected cells through direct cytolysis and release cytokines that influence other aspects of the immune system. Variations in KIR gene content and allelic variants have been associated with autoimmunity, transplantation success, and infectious diseases such as hepatitis C and HIV/AIDS. We investigated the impact of KIR genes and potential KIR-HLA …

Limited Transplantation Of Antigen-Expressing Hematopoietic Stem Cells Induces Long-Lasting Cytotoxic T Cell Responses And Effect Of Altered Suppressive Myeloid Population On Hiv-Disease Progression, Warren L. Denning

All ETDs from UAB

While each type of cancer and chronic viral infection has its own specific pathology, they share two common mechanisms of immune evasion. The first mechanism is the exhaustion or deletion of antigen-specific T cells. The second mechanism is the formation of an immunosuppressive environment responsible for the block of T cell function. Elicitation of antigen-specific T cells be accomplished by immunotherapy in place of conventional treatments such as HAART and chemotherapy. In addition, immunotherapy can alleviate the side-effects associated with long-term use of conventional therapies while reducing the total cost. The results presented here provide an alternative to conventional methods …

Inhibition Of Multi-Drug Resistant Hiv-1 Reverse Transcriptase By Nucleoside Beta-Triphosphates, Chandravanu Dash, Yousef Ahmadibeni, Michael J. Hanley, Jui Pandhare, Mathias Gotte, Stuart F. J. Le Grice, Keykavous Parang

Pharmacy Faculty Articles and Research

Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside β-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), and 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine β-triphosphate (1) and AZT β-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and nonnucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10 …

Safety Assessment For Tipranavir : A Protease Inhibitor Treatment For Hiv Infected Adults, Jaromir Mikl

Legacy Theses & Dissertations (2009 - 2024)

Dose-limiting adverse events associated with anti-retroviral therapy (ART) generally include gastro-intestinal (GI) issues such as vomiting and nausea. However, serious adverse events (SAEs) do occur, the most frequent of which include liver toxicities and renal impairment as well as recent evidence of cardio-vascular disease (CVD) risk.

The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar

All ETDs from UAB

Upon human immunodeficiency virus (HIV) infection the host mounts a robust and multifaceted immune response. To achieve successful replication, HIV must possess a powerful arsenal of immune evasion weapons. While a complex strategy for HIV immune evasion has been described in the periphery, little is known about the mechanism allowing HIV to overcome the simple interferon (IFN)-ß-mediated innate immune defenses of the central nervous system (CNS). In light of the devastating cognitive dysfunction that is caused by HIV replication within the CNS, a better understanding of this mechanism is critical. Recent studies have shown that viral pathogens can induce the …

Lipid Nanoparticles With Accessible Nickel As A Vaccine Delivery System For Single And Multiple His-Tagged Hiv Antigens, Weili Yan, Anekant Jain, Ronan O'Carra, Jerold Woodward, Wenxue Li, Guanhan Li, Avindra Nath, Russell J. Mumper

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the HIV his-tagged Tat protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by s.c. injection with his-Tat/Ni-NP formulation (1.5 μg Tat-his/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific IgG titer with his-Tat/Ni-NP was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity …

Serial Evolutionary Networks Of Within-Patient Hiv-1 Sequences Reveal Patterns Of Evolution Of X4 Strains, Patrica Buendia, Giri Narasimhan

School of Computing and Information Sciences

Background

The HIV virus is known for its ability to exploit numerous genetic and evolutionary mechanisms to ensure its proliferation, among them, high replication, mutation and recombination rates. Sliding MinPD, a recently introduced computational method [1], was used to investigate the patterns of evolution of serially-sampled HIV-1 sequence data from eight patients with a special focus on the emergence of X4 strains. Unlike other phylogenetic methods, Sliding MinPD combines distance-based inference with a nonparametric bootstrap procedure and automated recombination detection to reconstruct the evolutionary history of longitudinal sequence data. We present serial evolutionary networks as a longitudinal representation …

Long-Term Consequences Of The Delay Between Virologic Failure Of Highly Active Antiretroviral Therapy And Regimen Modification, Maya L. Petersen, Mark J. Van Der Laan, Napravnik Sonia, Joseph J. Eron, Richard G. Moore, Steven G. Deeks

Maya Petersen

Objectives: Current treatment guidelines recommend immediate modification of antiretroviral therapy in HIV-infected individuals with incomplete viral suppression. These recommendations have not been tested in observational studies or large randomized trials. We evaluated the consequences of delayed modification following virologic failure. Design/methods: We used prospective data from two clinical cohorts to estimate the effect of time until regimen modification following first regimen failure on all-cause mortality. The impact of regimen type was also assessed. As the effect of delayed switching can be confounded if patients with a poor prognosis modify therapy earlier than those with a good prognosis, we used a …

The Potential Role Of Probiotics In Reducing Poverty-Associated Infections In Developing Countries, Kingsley C. Anukam

Kingsley C Anukam

Probiotics are defined by the Food and Agricultural Organization/ World Health Organization as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” [1]. The potential benefits of their use have not been adequately investigated, especially in the developing world. Japan introduced Yakult, a probiotic fermented food drink in 1935, and in the Northern hemisphere, research and use of probiotics has gained an unprecedented momentum in the last decade [2]. Use of probiotics is not uncommon in Europe [3], but in many developing countries use of probiotics in its present definition is a foreign concept. …

Identifying Important Explanatory Variables For Time-Varying Outcomes., Oliver Bembom, Maya L. Petersen, Mark J. Van Der Laan

Maya Petersen

This chapter describes a systematic and targeted approach for estimating the impact of each of a large number of baseline covariates on an outcome that is measured repeatedly over time. These variable importance estimates can be adjusted for a user-specified set of confounders and lend themselves in a straightforward way to obtaining confidence intervals and p-values. Hence, they can in particular be used to identify a subset of baseline covariates that are the most important explanatory variables for the time-varying outcome of interest. We illustrate the methodology in a data analysis aimed at finding mutations of the human immunodeficiency virus …

Alpha Interferon Potently Enhances The Anti-Human Immunodeficiency Virus Type 1 Activity Of Apobec3g In Resting Primary Cd4 T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Guiseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-{alpha}/ß signal transduction pathway, IFN-{alpha} can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting …

Antioxidant Enzyme Gene Delivery To Protect From Hiv-1 Gp120-Induced Neuronal Apoptosis, Lokesh Agrawal, Jean-Pierre Louboutin, Beverly A.S. Reyes, Elisabeth J. Van Bockstaele, David S. Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120 exposure, and so might be protected from ROS-mediated injury by antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1). Both enzymes detoxify oxygen free radicals. Because they are highly efficient gene delivery vehicles for neurons, recombinant SV40-derived vectors were used for these studies. Cultured mature neurons derived from NT2 cells …

Orally Delivered, Plant-Produced Tat Protein Primes Mice For A Challenge Dna Vaccine Expressing Tat, A V. Karasev, S Foulke, C Wellens, I Zwierzynski, R Baldwin, H Koprowski, M S. Reitz Jr

Department of Microbiology and Immunology Faculty Papers

Oral Presentation.

Chemokine Receptor Cxcr4 Expression In The Major Salivary Gland, Çağri Deli̇lbaşi

Turkish Journal of Medical Sciences

LİLBAŞI Osaka University, Graduate School of Dentistry, First Department of Oral and Maxillofacial Surgery

Hiv Tat Protein Activates Endothelial Cells Through Nfκb And Map Kinase Pathways., Jason L. Henry

Electronic Theses and Dissertations

HIV infection has been shown to predispose patients to accelerated development of heart disease. One mechanism for this pathology may involve endothelial activation either by HIV itself or by its secreted proteins, gp120 (a viral envelope protein) and tat (a protein that upregulates transcription of viral genes). We have studied the effects of gp120 and tat on signaling and production of inflammatory cytokines by Human Pulmonary Artery Endothelial Cells (HPAEC). HPAEC were stimulated at varying time points with combinations of gp120, tat, and monokines (IL-1β and TNFα). Cell lysate fractions were analyzed for MAP Kinase activity and NFκB activation, and …