Medicine and Health Sciences Commons^™

Alcohol And Cannabinoids Differentially Affect Hiv Infection And Function Of Human Monocyte-Derived Dendritic Cells(Mddc), Marisela Agudelo, Gloria Figueroa, Adriana Yndart-Arias, Gianna Casteleiro, Karla Muñoz, Thangavel Samikkannu, Venkata Atluri, Madhavan P. Nair

HWCOM Faculty Publications

During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC). However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 …

A Team Reacts To A Patient’S Death, Suzanne Minor, Sanaz Kashan, Maite Castillo

HWCOM Faculty Publications

No abstract provided.

Triple Negative Breast Cancers Express Receptors For Lhrh And Are Potential Therapeutic Targets For Cytotoxic Lhrh-Analogs, Aezs 108 And Aezs 125, Stephen Seitz, Stefan Buchholz, Andrew Victor Schally, Florian Weber, Monika Klinkhammer-Schalke, Elizabeth C. Inwald, Roberto Perez, Ferenc G. Rick, Luca Szakontay, Florian Hohla, Sabine Segerer, Chui Wai Kwok, Olaf Ortmann, Jorg Bernhard Engel

HWCOM Faculty Publications

Background

Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer burdened with a dismal prognosis due to the lack of effective therapeutic agents. Receptors for LHRH (luteinizing hormone-releasing hormone) can be successfully targeted with AEZS-108 [AN-152], an analog of LHRH conjugated to doxorubicin. Our study evaluates the presence of this target LHRH receptor in human specimens of TNBC and investigates the efficacy and toxicity of AEZS-108 in vivo. We also studied in vitro activity of AEZS-125, a new LHRH analog conjugated with the highly potent natural compound, Disorazol Z.

Methods

69 human surgical specimens of TNBC were …

Mucociliary Dysfunction In Hiv And Smoked Substance Abuse, Srinivasan Chinnapaiyan, Hoshang J. Unwalla

HWCOM Faculty Publications

Impaired mucociliary clearance (MCC) is a hallmark of acquired chronic airway diseases like chronic bronchitis associated with chronic obstructive pulmonary disease (COPD) and asthma. This manifests as microbial colonization of the lung consequently leading to recurrent respiratory infections. People living with HIV demonstrate increased incidence of these chronic airway diseases. Bacterial pneumonia continues to be an important comorbidity in people living with HIV even though anti-retroviral therapy has succeeded in restoring CD4+ cell counts. People living with HIV demonstrate increased microbial colonization of the lower airways. The microbial flora is similar to that observed in diseases like cystic fibrosis and …

Downregulation Of Host Tryptophan-Aspartate Containing Coat (Taco) Gene Restricts The Entry And Survival Of Leishmania Donovani In Human Macrophage Model, Venkateswara Reddy Gogulamudi, Mohan Lal Dubey, Deepak Kaul, Venkata Atluri

HWCOM Faculty Publications

Leishmania are obligate intracellular protozoan parasites of mammalian hosts. Promastigotes of Leishmania are internalized by macrophages and transformed into amastigotes in phagosomes, and replicate in phagolysosomes. Phagosomal maturation arrest is known to play a crucial role in the survival of pathogenic Leishmania within activated macrophages. Recently, tryptophan-aspartate containing coat (TACO) gene has been recognized as playing a central role in the survival of Mycobacterium tuberculosis within human macrophages by arresting the phagosome maturation process. We postulated that a similar association of TACO gene with phagosomes would prevent the vacuole from maturation in the case of Leishmania. In this study we …

Interaction Of Drugs Of Abuse And Microrna With Hiv: A Brief Review., Sudheesh Pilakka-Kanthikeel, Madhavan P.N. Nair

HWCOM Faculty Publications

MicroRNAs (miRNAs), the post-transcriptional regulators of gene expression, play key roles in modulating many cellular processes. The changes in the expression profiles of several specific miRNAs affect the interactions between miRNA and their targets in various illnesses, including addiction, HIV, cancer etc. The presence of anti-HIV-1 microRNAs (which regulate the level of infectivity of HIV-1) have been validated in the cells which are the primary targets of HIV infection. Drugs of abuse impair the intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection. Emerging evidence has implicated miRNAs are differentially expressed in response to chronic morphine …

Preparation And Characterization Of Anti-Hiv Nanodrug Targeted To Microfold Cell Of Gut-Associated Lymphoid Tissue, Upal Roy, Hong Ding, Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Venkata Atluri, Adriana Yndart, Elena Kaftanovskaya, Elena Batrakova, Marisela Agudelo, Madhavan Nair

HWCOM Faculty Publications

The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host–pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a …

Role Of Mrp Transporters In Regulating Antimicrobial Drug Inefficacy And Oxidative Stress-Induced Pathogenesis During Hiv-1 And Tb Infections., Upal Roy, Paul Barber, Yuk-Ching Tse-Dinh, Elena V. Batrakova, Debasis Mondal, Madhavan Nair

HWCOM Faculty Publications

Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses …

Interactive Effects Of Cocaine On Hiv Infection: Implication In Hiv-Associated Neurocognitive Disorder And Neuroaids., Santosh Dahal, Sai V. P. Chitti, Madhavan Nair, Shailendra K. Saxena

HWCOM Faculty Publications

Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA …

Single-Incision Single-Instrument Adnexal Surgery In Pediatric Patients, Tara Loux, Gavin A. Falk, Michaela Gaffley, Stephanie Ortega, Leopoldo Malvezzi, Colin G. Knight, Cathy Burnweit

HWCOM Faculty Publications

Pediatric surgeons often practice pediatric gynecology.Thesingle-incision single-instrument (SISI) technique used for appendectomy is applicable in gynecologic surgery. Methods.We retrospectively analyzed the records of patients undergoing pelvic surgery from 2008 to 2013. SISI utilized a 12mm transumbilical trocar and an operating endoscope. The adnexa can be detorsed intracorporeally or extracorporealized via the umbilicus for lesion removal. Results. We performed 271 ovarian or paraovarian surgeries in 258 patients. In 147 (54%), the initial approach was SISI; 75 cases (51%) were completed in patients aged from 1 day to 19.9 years and weighing 4.7 to 117 kg. Conversion to standard laparoscopy was due …

Assessing The Prevalence Of Autoimmune, Endocrine, Gynecologic, And Psychiatric Comorbidities In An Ethnically Diverse Cohort Of Female Fibromyalgia Patients: Does The Time From Hysterectomy Provide A Clue?, Larry Brooks, Joseph Hadi, Kyle T. Amber, Christopher L. Lariche, Tamar Ference

HWCOM Faculty Publications

No abstract provided.

Activation Of Relaxin Family Receptor 1 From Different Mammalian Species By Relaxin Peptide And Small-Molecule Agonist Ml290, Zaohua Huang, Courtney Myhr, Ross A.D. Bathgate, Brian A. Ho, Xin Hu, Jingbo Xiao, Noel Southall, Elena Barnaeva, Irina U. Agoulnik, Juan J. Marugan, Marc Ferrer, Alexander I. Agoulnik

HWCOM Faculty Publications

Relaxin peptide (RLN), which signals through the relaxin family peptide 1 (RXFP1) GPCR receptor, has shown therapeutic effects in an acute heart failure clinical trial. We have identified a small-molecule agonist of human RXFP1, ML290; however, it does not activate the mouse receptor. To find a suitable animal model for ML290 testing and to gain mechanistic insights into the interaction of various ligands with RXFP1, we have cloned rhesus macaque, pig, rabbit, and guinea pig RXFP1s and analyzed their activation by RLN and ML290. HEK293T cells expressing macaque or pig RXFP1 responded to relaxin and ML290 treatment as measured by …

Non-Oral Drug Delivery Strategies: From Early Diagnosis To Advanced Treatments, Claudia Trenkwalder, Werner Poewe, Fabrizio Stocchi, Stuart H. Isaacson

HWCOM Faculty Publications

No abstract provided.

Dj1 Expression Downregulates In Neuroblastoma Cells (Sk-N-Mc) Chronically Exposed To Hiv-1 And Cocaine, Upal Roy, Venkata Atluri, Marisela Agudelo, Adriana Yndart, Zaohua Huang, Madhavan Nair

HWCOM Faculty Publications

Background: HIV-associated neurological disorder (HAND) has long been recognized as a consequence of human immunodeficiency virus (HIV) infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson’s disease) in regulating dopamine (DA) transmission and reactive oxygen species (ROS) production in neuronal cells will be worth investigating in …

Differing Roles Of Autophagy In Hiv-Associated Neurocognitive Impairment And Encephalitis With Implications For Morphine Co-Exposure, Seth M. Dever, Myosotys Rodriguez, Jessica Lapierre, Blair N. Costin, Nazira El-Hage

HWCOM Faculty Publications

We investigated the role of autophagy in HIV-infected subjects with neurocognitive impairment (NCI) ± HIV encephalitis (HIVE), many of which had a history of polysubstance abuse/dependence, using post-mortem brain tissues to determine whether differences in autophagy related factors may be more associated with NCI or NCI-encephalitis. Using qRT-PCR, we detected significant differences in gene expression levels with SQSTM1, LAMP1 higher in HIV-infected subjects without NCI while ATG5, SQSTM1 were then lower in HIV infection/NCI and ATG7, SQSTM1 being higher in NCI-HIVE. Immunohistochemical labeling of these autophagy associated proteins (also including Beclin 1 and LC3B) in Iba1-positive microglial cells showed generally …

Proliferative And Glycolytic Assessment Of The Whole-Body Bone Marrow Compartment, Mohammed Goryawala, Malek Adjouadi, Seza Gulec

HWCOM Faculty Publications

No abstract provided.

Fibonacci Series, Golden Proportions, And The Human Biology, Dharam Persaud, James P. O'Leary

HWCOM Faculty Publications

Pythagoras, Plato and Euclid’s paved the way for Classical Geometry. The idea of shapes that can be mathematically defined by equations led to the creation of great structures of modern and ancient civilizations, and milestones in mathematics and science. However, classical geometry fails to explain the complexity of non-linear shapes replete in nature such as the curvature of a flower or the wings of a Butterfly. Such non-linearity can be explained by fractal geometry which creates shapes that emulate those found in nature with remarkable accuracy. Such phenomenon begs the question of architectural origin for biological existence within the universe. …

New Therapies For Relapsed Castration-Resistant Prostate Cancer Based On Peptide Analogs Of Hypothalamic Hormones, Andrew V. Schally, Norman L. Block, Ferenc G. Rick

HWCOM Faculty Publications

It is a pleasure to contribute our presentation at the International Prostate Forum of the Annual Meeting of the American Urological Association (AUA) to this special issue of the Asian Journal of Andrology.

Hiv-1 Gp120 And Morphine Induced Oxidative Stress: Role In Cell Cycle Regulation, Thangaval Samikkannu, Deep Ranjith, Kurapati V.K. Rao, Venkata Alturi, Emely Pimentel, Nazira El-Hage, Madhavan Nair

HWCOM Faculty Publications

HIV infection and illicit drugs are known to induce oxidative stress and linked with severity of viral replication, disease progression, impaired cell cycle regulation and neurodegeneration. Studies have shown that morphine accelerates HIV infection and disease progression mediated by Reactive oxygen species (ROS). Oxidative stress impact redox balance and ROS production affect cell cycle regulation. However, the role of morphine in HIV associated acceleration of oxidative stress and its link to cell cycle regulation and neurodegeneration has not been elucidated. The aim of present study is to elucidate the mechanism of oxidative stress induced glutathione synthases (GSS), super oxide dismutase …

Assessing The Prevalence Of Autoimmune, Endocrine, Gynecologic, And Psychiatric Comorbidities In An Ethnically Diverse Cohort Of Female Fibromyalgia Patients: Does The Time From Hysterectomy Provide A Clue?, Larry Brooks, Joseph Hadi, Kyle T. Amber, Michelle Weiner, Christopher L. Lariche, Tamar Ference

HWCOM Faculty Publications

Background: This retrospective chart review investigated differences in the prevalence of medical comorbidity between women with fibromyalgia (FM) (n=219) and a control group women with chronic pain (CP) without FM (n=116). The specific aims were to compare the prevalence of autoimmune, psychiatric, endocrine, gynecologic pathology, the relationship between timing of gynecologic surgery, and pain onset. We additionally sought to compare the number of comorbidities in an ethnically diverse cohort.

Methods: This was a retrospective chart review of patients seen in FM or CP clinics at an academic medical center in 2009–2010.

Results: Logistic regression modeling found that gynecologic, endocrine, and …

Synaptic Plasticity And Neurological Disorders In Neurotropic Viral Infections, Venkata Atluri, Melissa Hidalgo, Thangavel Samikkannu, Kesava Rao Venkata Kurapati, Madhavan Nair

HWCOM Faculty Publications

Based on the type of cells or tissues they tend to harbor or attack, many of the viruses are characterized. But, in case of neurotropic viruses, it is not possible to classify them based on their tropism because many of them are not primarily neurotropic. While rabies and poliovirus are considered as strictly neurotropic, other neurotropic viruses involve nervous tissue only secondarily. Since the AIDS pandemic, the interest in neurotropic viral infections has become essential for all clinical neurologists. Although these neurotropic viruses are able to be harbored in or infect the nervous system, not all the neurotropic viruses have …

Effect Of Human Immunodeficiency Virus On Blood-Brain Barrier Integrity And Function: An Update, Venkata Atluri, Melissa Hidalgo, Thangavel Samikkannu, Kesava Rao Venkata Kurapati, Rahul Dev Jayant, Vidya Sagar, Madhavan Nair

HWCOM Faculty Publications

The blood-brain barrier (BBB) is a diffusion barrier that has an important role in maintaining a precisely regulated microenvironment protecting the neural tissue from infectious agents and toxins in the circulating system. Compromised BBB integrity plays a major role in the pathogenesis of retroviral associated neurological diseases. Human Immunodeficiency Virus (HIV) infection in the Central Nervous System (CNS) is an early event even before the serodiagnosis for HIV positivity or the initiation of antiretroviral therapy (ART), resulting in neurological complications in many of the infected patients. Macrophages, microglia and astrocytes (in low levels) are the most productively/latently infected cell types …

Hiv Subtypes B And C Gp120 And Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity, Thangavel Samikkannu, Kurapati V.K. Rao, Abdul Ajees Abdul Salam, Venkata Atluri, Elena Kaftanovskaya, Marisela Agudelo, Suray Perez, Changwon Yoo, Andrea Raymond, Hong Ding, Madhavan Nair

HWCOM Faculty Publications

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, …

Factors Affecting Compliance With Colorectal Cancer Screening Among Households Residing In The Largely Haitian Community Of Little Haiti, Miami-Dade County, Florida, Meredith Leigh Wilcox, Juan M. Acuna, Pura Rodríguez De La Vega, Grettel Castro, Purnima Madhivanan

HWCOM Faculty Publications

The United States Black population is disproportionately affected by colorectal cancer (CRC) in terms of incidence and mortality. Studies suggest that screening rates are lower among Blacks compared with non-Hispanic Whites (NHWs). However, studies on CRC screening within Black subgroups are lacking. This study examined disparities in blood stool test (BST) compliance and colonoscopy use by race/ethnicity (Haitian, NHW, non-Hispanic Black [NHB], and Hispanic) among randomly selected households in Little Haiti, Miami-Dade County, Florida.This study used cross-sectional, health and wellness data from a random-sample, population-based survey conducted within 951 households in Little Haiti between November 2011 and December 2012. BST …

Inclusion Of Neuropsychological Scores In Atrophy Models Improves Diagnostic Classification Of Alzheimer’S Disease And Mild Cognitive Impairment, Mohammed Goryawala, Qi Zhou, Warren Barker, David A. Lowenstein, Ranjan Duara

HWCOM Faculty Publications

Brain atrophy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) are difficult to demarcate to assess the progression of AD.This study presents a statistical framework on the basis of MRI volumes and neuropsychological scores. A feature selection technique using backward stepwise linear regression together with linear discriminant analysis is designed to classify cognitive normal (CN) subjects, early MCI (EMCI), late MCI (LMCI), and AD subjects in an exhaustive two-group classification process. Results show a dominance of the neuropsychological parameters like MMSE and RAVLT. Cortical volumetric measures of the temporal, parietal, and cingulate regions are found to be significant classification …

Effect Of Mild-To-Moderate Smoking On Viral Load, Cytokines, Oxidative Stress, And Cytochrome P450 Enzymes In Hiv-Infected Individuals, Anusha Ande, Carole Mcarthur, Leo Ayuk, Charles Awasom, Paul Ngang Achu, Annette Nijinda, Namita Sinha, P. S.S. Rao, Marisela Agudelo, Anantha Ram Nookala, Stephen Simon, Anil Kumar, Santosh Kumar

HWCOM Faculty Publications

Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not …

Sterile Alpha Motif And Histidine/Aspartic Acid Domain-Containing Protein 1 (Samhd1)-Facilitated Hiv Restriction In Astrocytes Is Regulated By Mirna-181a, Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Venkata Atluri, Vidya Sagar, Shaeilendra K. Saxena, Patricia Diaz, Semithe Chevelon, Michael Concepcion, Madhavan Nair

HWCOM Faculty Publications

Background

Although highly active antiretroviral therapy (HAART) has significantly reduced the morbidity and mortality in HIV patients, virus continues to reside in the central nervous system (CNS) reservoir. Hence, a complete eradication of virus remains a challenge. HIV productively infects microglia/macrophages, but astrocytes are generally restricted to HIV infection. The relative importance of the possible replication blocks in astrocytes, however, is yet to be delineated. A recently identified restriction factor, sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), restricts HIV infection in resting CD4⁺T cells and in monocyte-derived dendritic cells. However, SAMHD1 expression and HIV-1 restriction …

Drugs Of Abuse In Hiv Infection And Neurotoxicity, Melissa Hidalgo, Venkata Atluri, Madhavan Nair

HWCOM Faculty Publications

No abstract provided.

Spatial Positioning Of All 24 Chromosomes In The Lymphocytes Of Six Subjects: Evidence Of Reproducible Positioning And Spatial Repositioning Following Dna Damage With Hydrogen Peroxide And Ultraviolet B, Dimitrios Ioannou, Lakshmi Kandukuri, Ameer Quadri, Victor Becerra, Joe Leigh Simpson, Helen G. Tempest

HWCOM Faculty Publications

The higher-order organization of chromatin is well-established, with chromosomes occupying distinct positions within the interphase nucleus. Chromatin is susceptible to, and constantly assaulted by both endogenous and exogenous threats. However, the effects of DNA damage on the spatial topology of chromosomes are hitherto, poorly understood. This study investigates the organization of all 24 human chromosomes in lymphocytes from six individuals prior to- and following in-vitro exposure to genotoxic agents: hydrogen peroxide and ultraviolet B. This study is the first to report reproducible distinct hierarchical radial organization of chromosomes with little inter-individual differences between subjects. Perturbed nuclear organization was observed following …

Unusual Etiology For Upper Gastrointestinal Bleeding In A Previously Healthy Child, Madhuradhar Chegondi, Tara Loux, Balagangadhar R. Totapally, Cathy A. Burnweit

HWCOM Faculty Publications

Paraduodenal hernia (PDH) is the most common congenital internal hernia and rarely presents in pediatric age group with acute abdominal symptoms.We report a six year old boy who has recurrent vague abdominal pain, vomiting for six months and massive upper GI bleed at admission, found to have left sided PDH and small bowel ischemia intraoperatively and underwent small bowel resection and PDH repair. He was discharged from hospital on day 6 postoperative day after uneventful course.