Digital Commons Network^™

Synthesis And Evaluation Of Antiproliferative Activity Of Substituted N-(9-Oxo-9h-Xanthen-4-Yl)Benzenesulfonamides, Somayeh Motavallizadeh, Asal Fallah-Tafti, Saeedeh Maleki, Amir Nasrolahi Shirazi, Mahboobeh Pordeli, Maliheh Safavi, Sussan Kabudanian Ardestani, Shaaban Asd, Rakesh Tiwari, Donghoon Oh, Abbas Shafiee, Alireza Foroumadi, Keykavous Parang, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed …

Light Stimulates The Mouse Adrenal Through A Retinohypothalamic Pathway Independent Of An Effect On The Clock In The Suprachiasmatic Nucleus, Silke Kiessling, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The brain’s master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed …

Dens Agenesis And Cervical Vertebral Malformation In A Labrador Retriever Puppy, Elisa Salas, Henry E. Cerny, Seth P. Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

Cervical vertebral malformations can cause acute or progressive pain, paralysis, and potentially death. Herein we present a case report of dens agenesis; cervical vertebral malformations of C1, C2, C6, and C7; subluxation of C1 and C2 and C4 and C5; and associated degenerative myelopathy in a 5-month-old female Labrador Retriever puppy. We additionally review current knowledge regarding pathogenesis and treatment.

The Role Of Scavenger Receptor Class B Type I-Regulated Inducible Glucocorticoids In Sepsis, Junting Ai

Theses and Dissertations--Nutritional Sciences

Sepsis claims over 215,000 lives in the US annually. Inducible glucocorticoids (iGC) is produced during sepsis. However, the precise effects of iGC in sepsis remain unclear due to a lack of appropriate animal models. Glucocorticoid (GC) insufficiency is associated with a marked increase in mortality and occurs in 60% of severe septic patients. Yet the conclusion of GC therapy on septic patients is still controversial.

Scavenger receptor class B type I (SR-BI) in the adrenal mediates the selective uptake of cholesteryl ester from lipoproteins for GC synthesis. SR-BI-/- mice completely lack iGC during sepsis and are highly susceptible to septic …

Statistical Modeling Of Interfractional Tissue Deformation And Its Application In Radiation Therapy Planning, Douglas J. Vile

Theses and Dissertations

In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying …

Cyclic Peptide-Capped Gold Nanoparticles For Enhanced Sirna Delivery, Amir Nasrolahi Shirazi, Karissa L. Paquin, Niall G. Howlett, Dindyal Mandal, Keykavous Parang

Pharmacy Faculty Articles and Research

Previously, we have reported the synthesis of a homochiral L-cyclic peptide [WR]5 and its use for delivery of anti-HIV drugs and biomolecules. A physical mixture of HAuCl4 and the peptide generated peptide-capped gold nanoparticles. Here, [WR]5 and [WR]5-AuNPs were tested for their efficiency to deliver a small interfering RNA molecule (siRNA) in human cervix adenocarcinoma (HeLa) cells. Flow cytometry investigation revealed that the intracellular uptake of a fluorescence-labeled non-targeting siRNA (200 nM) was enhanced in the presence of [WR]5 and [WR]5-AuNPs by 2- and 3.8-fold when compared with that of siRNA alone after 24 h incubation. Comparative toxicity results showed …

Altered Mucins (Muc) Trafficking In Benign And Malignant Conditions., Suhasini Joshi, Sushil Kumar, Amit Choudhury, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density …

Novel Roles For Actin In Mitochondrial Fission, Anna L. Hatch, Pinar S. Gurel, Henry N. Higgs

Dartmouth Scholarship

Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynamin-related GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial …

Induction Of A Type I Interferon Signature In Normal Human Monocytes By Gadolinium-Based Contrast Agents: Comparison Of Linear And Macrocyclic Agents., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between …

Increased Incidence Of Asthma After Previous Infantile Rsv Bronchiolitis Infection, Ellen Adelia Doebler

Physician Assistant Scholarly Project Posters

• Respiratory Syncytial Virus (RSV) is a very common infection in children less than two years of age.

• Asthma is a common respiratory disease in childhood, which may cause frequent hospitalizations.

• The purpose of this study is to determine if infants previously diagnosed with RSV bronchiolitis have an increased incidence of asthma diagnosis compared to infants not diagnosed with RSV.

• The literature review examines correlation studies of both disease processes and explores incidence of asthma in patients previously diagnosed with Respiratory Syncytial Virus bronchiolitis.

• Individuals previously diagnosed with Respiratory Syncytial Virus bronchiolitis have a higher risk …

Importance Of Bacillithiol In The Oxidative Stress Response Of Staphylococcus Aureus, Ana C. Posada, Stacey L. Kolar, Renata G. Dusi, Patrica Francois

Dartmouth Scholarship

In Staphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed mutants with the deletion of bshA (sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, and fosB (sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains, including clinical isolates. Mutation of fosB or bshA caused a 16- to 60-fold reduction in fosfomycin resistance in these S. aureus strains. High-pressure liquid chromatography analysis, which …

Effect Of Ginkgo Biloba On Brain Volume After Carotid Artery Occlusion In Rats: A Stereological And Histopathological Study, Zeynep Aktürk, Ersan Odaci, Ayşe İki̇nci̇, Orhan Baş, Si̇nan Canpolat, Serdar Çolakoğlu, Osman Fi̇kret Sönmez

Turkish Journal of Medical Sciences

This study investigated the effect of Ginkgo biloba (GB) on brain volume in cerebral ischemia induced by stopping carotid artery blood flow. Materials and methods: Twenty-four adult male rats were divided into 4 groups of 6 rats each. No procedure was performed on the control group. Ischemia was applied to the rats in the ischemia and ischemia + GB groups by clamping the arteria carotis communis for 30 min. The rats in the ischemia + GB group were given 100 mg/kg drops (Tebokan Fort Drop, Abdi İbrahim İlaç Sanayi A.Ş., Turkey) containing dry GB leaf extract orally, every day for …

Comparison Of Hippocampal Interleukin-6 Immunoreactivity After Exhaustive Exercise In Both Exercise-Trained And Untrained Rats, Lati̇fe Arzu Aral, Lamia Pinar, Güleser Göktaş, Elçi̇n Yaşar Deveden, Deni̇z Erdoğan

Turkish Journal of Medical Sciences

Exhaustive exercise is a strong stress factor and can impact cytokine production in the brain. Interleukin-6 (IL-6) is produced in greater amounts than any other cytokine in response to exercise, and its effects are closely related to both exercise duration and intensity. In this study, we measured the differences between the amount of IL-6 reactivity of the hippocampus after an exhaustive session of running in long-term exercise-trained and untrained rats. Materials and methods: The exercise-trained group ran on a treadmill for 12 weeks. Both groups were forced to run until exhaustion. Each group of rats was sacrificed immediately, 1 day, …

The Role Of Hepcidin And Its Related Genes (Bmp6, Gdf-15, And Hjv) In Rats Exposed To Ischemia And Reperfusion, Recep Dokuyucu, Tuncer Demi̇r, Önder Yumrutaş, Ayşe Bi̇nnur Erbağci, Mustafa Örkmez, Abdulkadi̇r Yasi̇r Bahar, Recep Bayraktar, İbrahi̇m Bozgeyi̇k, Davut Si̇nan Kaplan, Beyhan Cengi̇z, Cahi̇t Bağci

Turkish Journal of Medical Sciences

To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. Materials and methods: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), …

Asymmetric Dimethyl Arginine Levels In Chronic Hemodialysis Patients, Aydin Çi̇fci̇, Sali̇h İnal, Coşkun Kaya

Turkish Journal of Medical Sciences

To investigate serum asymmetric dimethyl arginine (ADMA) levels in maintenance hemodialysis (HD) patients and to assess their potential correlations with C-reactive protein (CRP), albumin, and cholesterol levels as the established cardiovascular and nutritional parameters. Materials and methods: Forty-nine patients on maintenance HD treatment and 22 healthy volunteers with similar age and sex characteristics were recruited into the study. Serum albumin, CRP, creatinine, calcium, phosphate, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, hemoglobin, white blood cell counts, and serum ADMA levels were measured. Results: HD patients had significantly higher ADMA levels compared with healthy controls (0.51 ± 0.25 …

Genotype Distribution Of Hepatitis C Virus In Khorasan Razavi Province, Iran, Reza Afshari, Hosein Nomani, Fatemeh Riyahi Zaniani, Maryam Sadat Nabavinia, Zohreh Mirbagheri, Mojtaba Meshkat, Sina Gerayli, Sina Rostami, Zahra Meshkat

Turkish Journal of Medical Sciences

Several types of the hepatitis C virus (HCV), with variations in different parts of the genome, have been isolated from different regions of the world. Based on heterogenic sequences in the isolated genome, HCV is classified into different genotypes and subtypes. Data on distribution of HCV genotypes in a certain region could be important to patient management. Therefore, this study was conducted to determine the distribution of HCV in Mashhad, Northeast Iran. Materials and methods: This cross-sectional study was conducted on 103 patients with HCV infections in Mashhad. Among the participants, at least 22 (21.4%) were intravenous drug users. HCV …

Hormone Replacement Therapy-Related Changes In The Early Postmenopausal Period (Critical Window): An In Vivo Brain Proton Magnetic Resonance Spectroscopy Study, Kamran Mahmutyazicioğlu, Fahri̇ Hali̇t Beşi̇r, Mustafa Bardakçi, Hami̇t Alper Tanriverdi̇, Handan Ankarali

Turkish Journal of Medical Sciences

Findings from clinical studies in postmenopausal women with late initiation of hormone replacement therapy (HRT) that test whether HRT protects cognitive functions in women are inconsistent. The aim of this study was to investigate the effects of HRT on brain metabolite ratios when initiated in the early postmenopausal period (critical window). Materials and methods: Proton magnetic resonance spectrometry (1H MRS) was performed in 4 brain regions of 47 healthy postmenopausal women (21 received HRT, 26 did not). The subjects were aged between 45 and 65 years. The duration of HRT ranged from 1 to 12 years (mean: 6.3 years). The …

Behavioural And Neurobiological Consequences Of 2 Different Chronic Stressors In Rats, Refi̇a Aslihan Dönmez, Fatma Duygu Kaya, Okşan Deri̇nöz, Ömer Hakan Emmez, Selçuk Candansayar, Hayrunni̇sa Bolay Belen

Turkish Journal of Medical Sciences

To compare the behavioural and neurobiological consequences of chronic headache and chronic mild stress (CMS) in rats. Materials and methods: Forty-eight male Wistar rats were divided into 4 groups: 1) control group, 2) chronic headache group, 3) CMS group, and 4) sham group. Their behaviour prior to (D0) and after (D14) chronic stress was analysed. Afterwards, they were exposed to the Elevated Plus Maze (EPM) in order to evaluate anxiety-like behaviour and the Forced Swim Test (FST) for observation of depressive-like behaviour. Ultrasonic vocalisations (USVs) were recorded by a USV detector system at D0 and D14 and during the FST. …

Serum Fetuin-A Levels In Postmenopausal Women With Osteoporosis, Esi̇n Özkan, Hüseyi̇n Özkan, Serkan Bi̇lgi̇ç, Ersi̇n Odabaşi, Nuray Can, Emi̇n Özgür Akgül, İbrahi̇m Yanmiş, Yüksel Yurttaş, Mustafa Kürklü, Mustafa Başbozkurt, Mehmet Kemal Erbi̇l

Turkish Journal of Medical Sciences

One of the functions of fetuin-A is the restriction of formation and expansion of extraosseous hydroxyapatite crystals. The exact correlation of fetuin-A with bone mineral density (BMD) has not been clearly elucidated yet. In this study, we aimed to assess the relationship between BMD and fetuin-A in postmenopausal women. Materials and methods: Fifty postmenopausal women (25 with osteoporosis, 25 healthy controls) were included in the study. All participants were comparable for age and body mass index. None of the osteoporotic patients had received any medical treatment for osteoporosis. Serum fetuin-A levels were measured by ELISA method. Results: BMD scores of …

Possible Metabolic Impact Of Ramadan Fasting In Healthy Men, Mustafa Cumhur Vardarli, Hans-Peter Hammes, İrfan Vardarli

Turkish Journal of Medical Sciences

Insulin sensitivity and \beta-cell function during Ramadan fasting in healthy male subjects have not been investigated so far. We assessed the changes of these and other metabolic parameters to judge the potential metabolic benefits of Ramadan fasting. Materials and methods: Twenty-four healthy males of Turkish origin living in Germany, with normal glucose tolerance, participated in this study during Ramadan of 2009; 19 who completed fasting were analyzed. Blood was drawn at sunset after a period of fasting lasting approximately 15 h on days 0, 16, and 30 of Ramadan, as well as 7 and 28 days later. Insulin sensitivity (Homeostasis …

Prohepcidin In Maternal Circulation: Is It Related To Spontaneous Preterm Labor?, Yüksel Onaran, Esra Aktepe Keski̇n, Zehra Candan İltemi̇r Duvan, Serap Aynur Si̇mavli, Cemi̇le Koca, Hasan Kafali, Ni̇lgün Turhan

Turkish Journal of Medical Sciences

To investigate whether spontaneous preterm labor (PTL) with intact membranes is associated with changes in maternal serum prohepcidin concentrations. Materials and methods: The study consisted of patients with spontaneous PTL with intact membranes (n = 25), a control group of healthy pregnant women between the 24th and 37th gestational weeks (n = 22), and uncomplicated term pregnancies in spontaneous labor (n = 19). Blood samples were collected from patients at the time of clinical diagnosis. Levels of prohepcidin, hemoglobin, serum ferritin, serum iron, unsaturated iron binding capacity, total iron binding capacity, transferrin and transferrin saturation, C reactive protein, and interleukin-6 …

Distal Radius Measurements And Efficacy Of Fixed-Angle Locking Volar Plates, İsmai̇l Ağir, Mahmut Nedi̇m Ayteki̇n, Fati̇h Küçükdurmaz, Onur Başci, Ci̇hangi̇r Teti̇k

Turkish Journal of Medical Sciences

For surgical treatment of unstable distal radius fractures, fixed-angled locking volar plate fixation is becoming popular nowadays because of some advantages over other surgical techniques. In this article, we discuss the fitting of fixed-angle locking volar plates to the distal radius in relation to the changes in the distal radial angles. Materials and methods: First, we took conventional radiography images of 18 dried radii and later we measured the palmar subchondral angle, dorsal subchondral angle, mid-subchondral angle, and palmar cortical angle using lateral radiography. Results: According to the measurements, the volar subchondral angles (alpha) ranged from 10.2° to 28.1°, the …

Protective Roles Of Cimin Grape Tissues On Oxidative Stress Markers In The Cellular System Model, Hüseyi̇n Avni̇ Uydu, Ari̇fe Pinar Eki̇nci̇, Mehtap Atak, Adem Demi̇r

Turkish Journal of Medical Sciences

To analyze the phenolic composition of the Cimin grape, which is 1 of 2 grape varieties with a protected geographical indication in Turkey and is used locally to treat the symptoms of some disorders such as impotence and cardiovascular diseases, and to investigate its antioxidant potency against oxidant mediators in the models of intra- and extracellular surroundings. Materials and methods: Cimin grape samples were classified into 5 groups according to the grape's tissues and the extraction solvents used. Free radical scavenging (DPPH) and antilipid peroxidation product [thiobarbituric acid reactive substance (TBARS) and conjugated diene (CD)] levels of the grape tissues …

Evaluation Of Malaria Cases In Individuals After Traveling To Endemic Regions Of The World, Hülya Çaşkurlu, Emi̇ne Pakir, Aslihan Çolak

Turkish Journal of Medical Sciences

This study evaluates types of malaria and treatment success in a series of identified cases among individuals who were presumed to have travelled to regions where malaria is endemic. Materials and methods: In Sema Hospital, 25 cases of malaria (5 in women, 20 in men) were diagnosed during the 6-year period between 2006 and 2012. The mean age of the patients was 34.5 years. Diagnoses were established with thick and thin peripheral blood smears that were parasite-positive. These tests were then compared to the rapid diagnostic test based on Plasmodium falciparum histidine-rich protein 2. Results: All cases demonstrated fever beginning …

Mefv Mutation Frequency And Effect On Disease Severity In Ankylosing Spondylitis, Yüksel Maraş, Ali̇ Akdoğan, Bünyami̇n Kisacik, Levent Kiliç, Engi̇n Yilmaz, Abdurrahman Tufan, Umut Kalyoncu, Şazi̇ye Şule Apraş Bi̇lgen, Sedat Ki̇raz, Ali̇ İhsan Ertenli̇, Meral Çalgüneri̇

Turkish Journal of Medical Sciences

To define the frequency of familial Mediterranean fever gene (MEFV) mutations in ankylosing spondylitis (AS) and describe different clinical aspects of MEFV mutation carrier and noncarrier AS patients. Materials and methods: In 112 AS patients, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were calculated. The frequencies of 12 different MEFV mutations were studied by multiplex polymerase chain reaction/reverse hybridization method and were compared to those of previously studied healthy controls for 5 common MEFV mutations. Results: MEFV mutations were identified in 46 of 224 (20%) alleles and in 39 (35%) of AS …

Protective Effect Of L-Carnitine In A Rat Model Of Retinopathy Of Prematurity, Sadullah Keleş, İbrahi̇m Caner, Orhan Ateş, Özgür Çakici, Fati̇h Saruhan, Uğur Yilmaz Mumcu, Deni̇z Ünal, Kadi̇r Şerafetti̇n Tekgündüz, Ayhan Taşteki̇n, Ahmet Hacimüftüoğlu, Nesri̇n Gürsan, Hami̇t Hakan Alp

Turkish Journal of Medical Sciences

To investigate the effects of L-carnitine (LC) on rats with oxygen-induced retinopathy. Materials and methods: The study was conducted on 40 Sprague Dawley rat pups. The rat pups were randomly divided into 4 groups: group 1 (n = 10), the healthy control group with intraperitoneal 0.1 mL/day physiological saline injection; group 2 (n = 10), exposed to hyperoxygen, did not receive LC but received 0.1 mL/day physiological saline intraperitoneally; group 3 (n = 10), exposed to hyperoxygen and received 100 mg/kg/day LC intraperitoneally; group 4 (n = 10), exposed to hyperoxygen and received 200 mg/kg/day LC intraperitoneally. After postnatal day …

Novel Gammaherpesvirus Functions 1 Encoded By Bovine Herpesvirus (Bovine Lymphotropic Virus), J. Jia, G. Delhon, E. R. Tulman, D. G. Diel, Fernando A. Osorio, X. Wen, G. F. Kutish, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

The genus Macavirus of the subfamily Gammaherpesvirinae includes viruses that infect lymphoid cells of domestic and wild ruminants and swine, causing asymptomatic latent infections in reservoir hosts. Here, we describe the genome of bovine herpesvirus 6 (BoHV-6), a

macavirus ubiquitous in healthy cattle populations. The BoHV-6 genome exhibited architecture conserved in macaviruses, including a repetitive H-DNA region and unique, 141 kilobase pair L

DNA region predicted to encode 77 genes. BoHV-6 encoded in variable genomic regions a novel complement of genes relative to other characterized macaviruses, likely contributing to distinctive aspects of BoHV-6 infection biology and host range. Most notably, …

An Evolutionary Perspective On Infectious And Chronic Disease, John Eberth

Theses and Dissertations

The integration of evolutionary biology with traditional medicine can elucidate novel mechanisms of contemporary disease. Whereas the goal of traditional medicine is to treat and cure the proximate causes, evolutionary biology aims to understand the driving forces behind why humans are susceptible to disease. To form the basis of this hypothesis we postulate that modern man's current genetic information was programmed at a time, and in an environment, that is not relevant to today's human populations. The discordance between these genes of our ancestors and the environment of contemporary humans is thought to be a major reason for the increase …

The Role Of Microrna In Staphylococcal Enterotoxin B-Induced Inflammation And Acute Lung Injury, Roshni Rao

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a potent activator of the Vβ8+T-cells leading to the proliferation of nearly 30% of the T-cell pool. As a consequence, excessive amounts of cytokine mediators are released leading to extensive tissue damage and sometimes toxic shock and death. Due to the ease with which SEB can be aerosolized anddisseminated, it is considered a biological weapon. In the current study, we investigated the pro-inflammatory effects of SEB in two mouse models of acute inflammatory lung injury. Specifically, while inflammatory cues are known to elicit changes in key transcriptional factors and gene expression, we explored for the …

The Effect Of Gaba A Antagonism On Locomotor Activity And Dopamine Release In The Mouse Caudate Putamen Following Acute Toluene Inhalation: An In-Vivo Microdialysis Study, Sean Callan

Wayne State University Theses

Toluene is ubiquitous solvent commonly inhaled recreationally. Despite its frequency of misuse, there is little understanding of how toluene acts within the brain. To examine this, this master's thesis examined the impact of acutely inhaled toluene on dopamine (DA) release in the mouse CPu in vivo using microdialysis techniques. Toluene inhalation produced dose-dependent increases in DA levels as well as changes in locomotor activity. These effects were potentiated by pre-treatment with the GABAA antagonist bicuculline via reverse microdialysis delivery. These results suggest that the DA dynamics of toluene abuse are related to toluene's previously explored effects on the GABA system. …