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An Eye Opener In Stroke: Mitochondrial Dysfunction And Stem Cell Repair In Stroke-Induced Retinal Ischemia, Hung Vu Thien Nguyen

USF Tampa Graduate Theses and Dissertations

Stoke is a leading cause of disability and mortality across the globe, making it a global health crisis. However, treatments for stroke remain limited with narrow therapeutic time window. Visual impairment negatively affects patients’ quality of life. During stroke, the disruption in blood flow might affect both brain and eye resulting in cerebral and retinal ischemia. Currently, there is a lack of treatment option that targets both cerebral and retinal ischemia. Ischemic stroke pathology is complex and multiphasic. The ischemic event is followed by a secondary cascade of inflammatory cytokines exacerbating the initial focal injury and expanding into the penumbra. …

Single-Cell Glia And Neuron Gene Expression In The Central Amygdala In Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis, Sean J. O'Sullivan, Evangelia Malahias, James Park, Ankita Srivastava, Beverly A.S. Reyes, Jonathan Gorky, Rajanikanth Vadigepalli, Elisabeth J. Van Bockstaele, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably Tnf, were upregulated in the withdrawal condition and that astrocytes, in particular, were highly …

Circuit-Specific Control Of The Medial Entorhinal Inputs To The Dentate Gyrus By Atypical Presynaptic Nmdars Activated By Astrocytes, Iaroslav Savtchouk, Maria Amalia Di Castro, Rugina Ali, Hiltrud Stubbe, Rafael Lujan, Andrea Volterra

Biomedical Sciences Faculty Research and Publications

Here, we investigated the properties of presynaptic N-methyl-D-aspartate receptors (pre-NMDARs) at corticohippocampal excitatory connections between perforant path (PP) afferents and dentate granule cells (GCs), a circuit involved in memory encoding and centrally affected in Alzheimer’s disease and temporal lobe epilepsy. These receptors were previously reported to increase PP release probability in response to gliotransmitters released from astrocytes. Their activation occurred even under conditions of elevated Mg²⁺ and lack of action potential firing in the axons, although how this could be accomplished was unclear. We now report that these pre-NMDARs contain the GluN3a subunit conferring them low Mg^{2+ …}

Infection Potential Of Rickettsia Felis Via Ingestion, Matthew M. Schexnayder

LSU Master's Theses

Rickettsia felis is the etiologic agent of flea-borne spotted fever (FBSF) in humans and a poorly described cause of fever in animals. It is transmitted by its primary arthropod vector and reservoir host, the cat flea Ctenocephalides felis. Known routes of Rickettsia felis transmission between Rickettsia felis-infected cat fleas and vertebrate hosts include cutaneous bites and contamination of cutaneous wounds with infective flea feces. The bulk of FBSF infections occur in young children in Africa, though infections of people at all ages all over the world have been confirmed. As mammals and young children frequently come into contact …

Macaque Anterior Cingulate Cortex Deactivation Impairs Performance And Alters Lateral Prefrontal Oscillatory Activities In A Rule-Switching Task, Liya Ma, Jason L. Chan, Kevin Johnston, Stephen G. Lomber, Stefan Everling

Brain and Mind Institute Researchers' Publications

© 2019 Ma et al. In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy during maintenance of—but not the initial switching to—the cognitively demanding antisaccade rule, which coincided with a …

Ion Gresser 1928-2019, Jan Vilcek, Howard A. Young

United States Public Health Resources

Ion Gresser, a virologist who transformed understanding of the roles of interferons, may be best remembered for showing that in mice, interferon-α (IFN-α) can produce acute and chronic disease. At the time Gresser began these studies, interferon was considered to be a selective antiviral substance, harmless to uninfected cells and organisms, and there was no indication that cytokines would play a role in pathogenesis. That belief was shattered with the 1975 Nature publication with the simple title “Lethality of interferon preparations for newborn mice.” Gresser subsequently demonstrated that antibodies to IFN-α can protect young mice from death caused by infection …

Genetically Distinct Behavioral Modules Underlie Natural Variation In Thermal Performance Curves, Gregory W. Stegeman, Scott E. Baird, William S. Ryu, Asher D. Cutter

Biological Sciences Faculty Publications

Thermal reaction norms pervade organismal traits as stereotyped responses to temperature, a fundamental environmental input into sensory and physiological systems. Locomotory behavior represents an especially plastic read-out of animal response, with its dynamic dependence on environmental stimuli presenting a challenge for analysis and for understanding the genomic architecture of heritable variation. Here we characterize behavioral reaction norms as thermal performance curves for the nematode Caenorhabditis briggsae, using a collection of 23 wild isolate genotypes and 153 recombinant inbred lines to quantify the extent of genetic and plastic variation in locomotory behavior to temperature changes. By reducing the dimensionality of the …

Enhancing Cell Seeding And Osteogenesis Of Mscs On 3d Printed Scaffolds Through Injectable Bmp2 Immobilized Ecm-Mimetic Gel, Farahnaz Fahimipour, Erfan Dashtimoghadam, Mohammad Mahdi Hasani-Sadrabadi, Jessica Vargas, Daryoosh Vashaee, Doug Lobner, Tahereh S. Jafarzadeh Kashi, Behnam Ghasemzadeh, Lobat Tayebi

Biomedical Sciences Faculty Research and Publications

Objective

Design of bioactive scaffolds with osteogenic capacity is a central challenge in cell-based patient-specific bone tissue engineering. Efficient and spatially uniform seeding of (stem) cells onto such constructs is vital to attain functional tissues. Herein we developed heparin functionalized collagen gels supported by 3D printed bioceramic scaffolds, as bone extracellular matrix (ECM)-mimetic matrices. These matrices were designed to enhance cell seeding efficiency of mesenchymal stem cells (MSCs) as well as improve their osteogenic differentiation through immobilized bone morphogenic protein 2 (BMP2) to be used for personalized bone regeneration.

Methods

A 3D gel based on heparin-conjugated collagen matrix capable of …

The Contribution Of Adipose Tissue From Ovariectomized Mice To Colon Cancer, Meredith Smith Carson

Theses and Dissertations

Obesity is considered a major public health concern worldwide due to the increased incidences of metabolic dysfunction and cancer risk. The obese state is, in part, attributable to the overconsumption of calorie-dense foods commonly seen in a standard Western diet, which aids in the progression of chronic, lowgrade inflammation. The role of estrogen varies depending on menopausal status, where estrogen deficiency coupled with increased visceral fat associated with post-menopause leads to increased secretions of pro-inflammatory adipokines and cytokines. However, the presence of estrogen in a premenopausal state has been shown to attenuate the pro-inflammatory response, which has been demonstrated when …

Role Of Epigenome And Microbiome In Cannabinoid And Aryl Hydrocarbon Receptor-Mediated Regulation Of Inflammatory And Autoimmune Diseases, Zinah Zamil Al-Ghezi

Theses and Dissertations

Inflammation is considered to be the underlying cause of a majority of clinical disorders. Thus, studies aimed at understanding the signaling pathways that trigger inflammation could have significant translational impact. In the current study, we investigated the effect of activation of cannabinoid (CB) and Aryl hydrocarbon hydroxylase (AhR) receptors on the inflammatory response. To that end, we used cannabinoids such as Δ (9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD), and a well-established AhR agonist namely 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). These were tested against two inflammatory disease models: 1) Experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis (MS), and 2) Exposure to …

Macrophages And Associated Inflammation Differentially Impact Obesity, Colorectal Cancer And Obesity-Enhanced Colorectal Cancer, Jackie Bader

Theses and Dissertations

Colorectal Cancer (CRC) is the third-most common malignancy for men or women, with chronic inflammation considered as a primary risk factor. Obesity is also considered a chronic inflammatory disease and is associated with increased CRC incidence. Further, obesity and CRC occur in men and women differently with the highest incidence of either disease found in men, suggesting that female sex hormones may play a protective role in inflammatory diseases. Macrophages can promote inflammation and are a driving force in obesity-associated metabolic dysfunction. Conversely, macrophages also contribute to pro-tumoral responses including, proliferation, angiogenesis and tissue remodeling. This heterogeneity of macrophage behavior …

Role Of Epigenome And Microbiome In Endocannabinoid-Mediated Regulation Of Inflammation During Diet-Induced Obesity, Kathryn Miranda

Theses and Dissertations

Obesity is an inflammatory disease involving accumulation of adipose tissue, gut microbiota dysbiosis, and over-activation of the endocannabinoid system (ECS). Mechanisms involved in ECS regulation of obesity-induced inflammation are not well understood. Presented here are three chapters involving microRNA (miR) regulation of inflammatory adipose tissue macrophages (ATM) during high-fat diet (HFD)-induced obesity and cannabinoid receptor-mediated regulation of gut microbiota dysbiosis.

ATMs are innate immune cells that drive chronic low-grade inflammation during obesity. Polarization between pro-(M1) and anti-(M2-like) inflammatory phenotypes influence insulin sensitivity and energy expenditure; however, the mechanisms involved are unclear. In study one, we characterized miRs involved in ATM …

Effect Of Tcdd, An Environmental Contaminant, On Activation Of Ahr Leading To Induction Of Myeloid Derived Suppressor Cells (Mdscs) And The Ability Of Resveratrol, A Botanical, To Neutralize This Effect, Wurood Hantoosh Neamah

Theses and Dissertations

Aryl hydrocarbon receptor (AhR), is a ligand-activated transcription factor that integrates environmental, dietary, microbial and metabolic cues to control various cellular processes, such as the cell cycle, epithelial barrier function, cell migration and immune function. AhR was discovered as the receptor that binds with high affinity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leads to numerous of toxicological outcomes. In the current study, we discovered a critical role played by AhR, following activation by TCDD, in modulating a variety of immunological functions through regulation of epigenetic and microbial pathways. Our data demonstrated that AhR activation triggers MDSC mobilization from bone marrow to peritoneal …

Microrna-374a, -4680, And -133b Suppress Cell Proliferation Through The Regulation Of Genes Associated With Human Cleft Palate In Cultured Human Palate Cells

Faculty, Staff and Student Publications

BACKGROUND: Cleft palate (CP) is the second most common congenital birth defect; however, the relationship between CP-associated genes and epigenetic regulation remains largely unknown. In this study, we investigated the contribution of microRNAs (miRNAs) to cell proliferation and regulation of genes involved in CP development.

METHODS: In order to identify all genes for which mutations or association/linkage have been found in individuals with CP, we conducted a systematic literature search, followed by bioinformatics analyses for these genes. We validated the bioinformatics results experimentally by conducting cell proliferation assays and miRNA-gene regulatory analyses in cultured human palatal mesenchymal cells treated with …

Updated Genes, Lifestyles, And Their Interactions For Human Longevity, Brenda Bin Su, Alexis Villafranca, Chunxiang Mao, Stephanie Hernandez, Stephanie Lozano, Masoud M. Zarei, Kesheng Wang, Saraswathy Nair, Chun Xu

Health & Biomedical Sciences Faculty Publications

Healthy aging is the prolonging of optimal wellbeing during the progressive decline in physiological functions that are necessary for survival. Two important components of aging include an individual’s genetic makeup and lifestyle choices such as diet and exercise. Genetic factors are responsible for the functional physiology of the body including cell maintenance, metabolism and apoptosis. The individual effects of genes and lifestyle choices on aging are reported mainly in Caucasian populations, with very limited studies in minority populations. In this review, we included the effects of genes and environment and the interaction between them on aging in Hispanic population in …

The Expression Of Connexin-43 By Cd11c+ Dendritic Cells Is Required To Maintain Cd4+ Foxp3+ Regulatory T Cell Population In Peripheral Lymphoid Organs, Caroline Titus Miller

Biological Sciences Theses & Dissertations

Foxp3⁺ regulatory T cells (T_R) are an immunosuppressive subset of CD4⁺ T cells that maintain homeostasis of the immune system. They are sustained by the interaction between the Major Histocompatibility Complex (MHC) molecules present on antigen presenting dendritic cells and the T Cell Receptor (TCR) expressed on T_R cells that is specific for the MHC loaded with an antigenic peptide. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR cell population. CD11c⁺ dendritic cells represent a major subset of antigen presenting cells. …

Drug Interactions Between Direct-Acting Oral Anticoagulants And Calcineurin Inhibitors During Solid Organ Transplantation: Considerations For Therapy, Edwin Lam, Babar Bashir, Mark Chaballa, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Introduction: There is a high incidence of venous thromboembolism (VTE) in solid organ transplant recipients. The safety and efficacy of direct-acting oral anticoagulants (DOAC) have been well established in clinical practice for the prevention and treatment of VTE in broad populations. However, the management of VTE in the setting of solid organ transplantation remains a challenge to clinicians due to limited evidence of DOAC usage with calcineurin inhibitors.

Areas covered: The current literature available on the pharmacokinetic-pharmacodynamic interaction between DOACs and calcineurin inhibitors is presented. A comprehensive review was undertaken using PubMed, Embase, drug product labeling, and drug …

Behavioral Responses To Gold Nanoparticle Exposure And H2o2-Induced Oxidative Stress In Caenorhabditis Elegans, Rachel Pride, Ashley Wagner

DePaul Discoveries

Gold nanoparticles (AuNPs) have been utilized in many biomedical disciplines, most notably cancer therapy and drug delivery. Recent research suggests that with specific peptide manipulation, AuNPs can deliver drugs across the blood-brain barrier (BBB), allowing for treatment of neurodegeneration and other neurological afflictions. Neurodegeneration has been shown to be caused by oxidative stress. The present experiment aimed to assess the effects of AuNPs on C. elegans behavior that had undergone H₂O₂-induced oxidative stress. It was predicted that worms exposed to both H₂O₂ and AuNPs would have higher survival, mechanosensation, and thrashing rates than …

Nrxn1 Deletion And Exposure To Methylmercury Increase Astrocyte Differentiation By Different Notch-Dependent Transcriptional Mechanisms, Marilena Raciti, Salma Jahan, Stefan Spulber, Giulia Gaudenzi, Zahra Khalajzeyqami, Mirko Conti, Britt-Marie Anderlid, Anna Falk, Ola Hermans, Sandra Ceccatelli

Centre for Regenerative Medicine & Stem Cell Research

Controversial evidence points to a possible involvement of methylmercury (MeHg) in the etiopathogenesis of autism spectrum disorders (ASD). In the present study, we used human neuroepithelial stem cells from healthy donors and from an autistic patient bearing a bi-allelic deletion in the gene encoding for NRXN1 to evaluate whether MeHg would induce cellular changes comparable to those seen in cells derived from the ASD patient. In healthy cells, a subcytotoxic concentration of MeHg enhanced astroglial differentiation similarly to what observed in the diseased cells (N1), as shown by the number of GFAP positive cells and immunofluorescence signal intensity. In both …

Chronic Nucleoside Reverse Transcriptase Inhibitors Disrupt Mitochondrial Homeostasis And Promote Premature Endothelial Senescence, Yi-Fan Chen

LSU Doctoral Dissertations

Combination antiretroviral therapy (cART) has been hugely successful in reducing the mortality associated with human immunodeficiency virus (HIV) infection, resulting in a growing population of people living with HIV (PLWH). Since PLWH now have a longer life expectancy, chronic comorbidities have become the focus of the clinical management of HIV. For example, cardiovascular complications are now one of the most prevalent causes of death in PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and two NRTIs are typically used in combination with one drug from another drug class, such as a non-NRTI, a protease inhibitor or an …

A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter

Department of Biological Sciences Publications

Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc² 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc² 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc² 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc² 155 found to …

Failure Of Oxysterols Such As Lanosterol To Restore Lens Clarity From Cataracts, Damian M. Daszynski, Puttur Santhoshkumar, Ashutosh S. Phadte, K. Krishna Sharma, Haizhen A. Zhong, Marjorie F. Lou, Peter F. Kador

School of Veterinary and Biomedical Sciences: Faculty Publications

The paradigm that cataracts are irreversible and that vision from cataracts can only be restored through surgery has recently been challenged by reports that oxysterols such as lanosterol and 25-hydroxycholesterol can restore vision by binding to αB-crystallin chaperone protein to dissolve or disaggregate lenticular opacities. To confirm this premise, in vitro rat lens studies along with human lens protein solubilization studies were conducted. Cataracts were induced in viable rat lenses cultured for 48 hours in TC-199 bicarbonate media through physical trauma, 10 mM ouabain as Na+/K+ ATPase ion transport inhibitor, or 1 mM of an experimental compound that induces water …

Gm1 Ganglioside Modifies Α-Synuclein Toxicity And Is Neuroprotective In A Rat Α-Synuclein Model Of Parkinson's Disease., Jay S. Schneider, Radha Aras, Courtney K. Williams, James B. Koprich, Jonathan M. Brotchie, Vikrant Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While GM1 may interact with α-synuclein in vitro to inhibit aggregation, the ability of GM1 to protect against α-synuclein toxicity in vivo has not been investigated. We used targeted adeno-associated viral vector (AAV) overexpression of human mutant α-synuclein (A53T) in the rat substantia nigra (SN) to produce degeneration of SN dopamine neurons, loss of striatal dopamine levels, and behavioral impairment. Some animals received daily GM1 ganglioside administration for 6 weeks, beginning 24 hours after AAV-A53T administration or delayed start GM1 administration for 5 weeks beginning 3 weeks after AAV-A53T administration. Both types of GM1 administration protected against loss of SN …

The Need To Codify Roe V. Wade: A Case For National Abortion Legislation, Kathryn N. Peachman

Journal of Legislation

No abstract provided.

Activation Of Lxr Receptors And Inhibition Of Trap1 Causes Synthetic Lethality In Solid Tumors, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Elena Bianchetti, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

Cholesterol is a pivotal factor for cancer cells to entertain their relentless growth. In this case, we provide a novel strategy to inhibit tumor growth by simultaneous activation of liver-X-receptors and interference with Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1). Informed by a transcriptomic and subsequent gene set enrichment analysis, we demonstrate that inhibition of TRAP1 results in suppression of the cholesterol synthesis pathway in stem-like and established glioblastoma (GBM) cells by destabilizing the transcription factor SREBP2. Notably, TRAP1 inhibition induced cell death, which was rescued by cholesterol and mevalonate. Activation of liver X receptor (LXR) by a clinically validated …

Cyclin C Regulated Oxidative Stress Responsive Transcriptome In Mus Musculus Embryonic Fibroblasts, David C Stieg, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The transcriptional changes that occur in response to oxidative stress help direct the decision to maintain cell viability or enter a cell death pathway. Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively …

Extreme Events Reveal An Alimentary Limit On Sustained Maximal Human Energy Expenditure, Caitlin Thurber, Lara R. Dugas, Cara Ocobock, Bryce Carlson, John R. Speakman, Herman Pontzer

Publications and Research

The limits on maximum sustained energy expenditure are unclear but are of interest because they constrain reproduction, thermoregulation, and physical activity. Here, we show that sustained expenditure in humans, measured as maximum sustained metabolic scope (SusMS), is a function of event duration. We compiled measurements of total energy expenditure (TEE) and basal metabolic rate (BMR) from human endurance events and added new data from adults running ~250 km/week for 20 weeks in a transcontinental race. For events lasting 0.5 to 250+ days, SusMS decreases curvilinearly with event duration, plateauing below 3× BMR. This relationship differs from that of shorter events …

Roles Of Gm-Csf In The Pathogenesis Of Autoimmune Diseases: An Update., Noushin Lotfi, Rodolfo Thome, Nahid Rezaei, Guang-Xian Zhang, Abbas Rezaei, A. M. Rostami, Nafiseh Esmaeil

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) …

Investigating Trail Sensitivity In Platinum-Resistant Ovarian Cancer, Nicholas Pathoulas

All College Thesis Program, 2016-2019

Ovarian cancer is the deadliest gynecologic malignancy in the United States. While these tumors may have a promising initial response to platinum-based chemotherapies, the patient’s prognosis is commonly hindered by the development of platinum resistant cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been implicated as a potential treatment for many cancers based on its tumor selective nature. Combination therapies with TRAIL and platinum drugs have been shown to increase apoptosis and have been used in a variety of clinical trials, which have thus far failed to pass phase II.1 Researchers have not yet elucidated the complex mechanism(s) of TRAIL …

Effect Of Sildenafil On Stable Chronic Heart Failure: A Prospective Randomized-Controlled Clinical Trial, Hatem Khairy, Wael Abdelatief Elhakeem

Journal of Medicine in Scientific Research

Background Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension have reduced exercise capacity and increased mortality compared with HF patients without pulmonary hypertension. A defective nitric oxide signaling is involved in left ventricular (LV) diastolic abnormalities and remodeling. Phosphodiesterase type 5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. Aim of the study In our study, we tested the effects of phosphodiesterase type 5 inhibition (sildenafil) on LV ejection fraction, diastolic function, pulmonary artery pressure, and clinical status. Patients, methods, and results One hundred HF patients (New York Heart Association classes …