Digital Commons Network^™

New Insights Into The Androgen-Targeted Therapies And Epigenetic Therapies In Prostate Cancer., Abhijit M Godbole, Vincent C O Njar

Kimmel Cancer Center Faculty Papers

Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The androgen receptor (AR), a receptor of nuclear family and a transcription factor, is the most important target in this disease. While most efforts in the clinic are currently directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributable to this castration-resistant form of prostate cancer (CRPC). Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling …

Seasonal Affective Disorder: Sad Or Fad?, J. Thomas Pichot, Md, Peter S. Jensen, Md

Jefferson Journal of Psychiatry

Seasonal affective disorder (SAD) and phototherapy have recently been the subject of a great deal of interest in the psychiatric literature. First described in 1984 (I), SAD is now defined as "a cyclic illness characterized by recurrent episodes of fall/winter depression alternating with periods of spring/summer euthymia (normal mood) or hypomania (mild elation and behavioral activation)" (2) . Recent findings indicate that there may be at least two additional patterns of seasonal depressions, one characterized by annual summer depressions with euthyrnic, hypomanic or manic symptoms in the winter, and the other characterized by depressive episodes occurring in both winter and …

Brief Remarks On Some Linguistic Features Of "Empathy" And "Sympathy", Emanuel E. Garcia, Md

Jefferson Journal of Psychiatry

The use of words by an individual or culture is subject to the very same psychological forces that drive man's other activities . Hence, the history of a word's usage becomes a telling record of the mental processes of its creators and users, both conscious and unconscious. Etymology, as Freud has observed in his dreambook (1900), contributes significantly to our understanding of the deeper layers of the psyche . Let us take the word "rival," for example, and see how we may make use of etymological data. It is derived from the Latin "riva lis," I which originally meant "one …

Mechanisms And Therapeutic Implications Of Neuroleptic Atypicality, Daniel C. Javitt, Md

Jefferson Journal of Psychiatry

Neuroleptics have proven effective for the overall treatment of schizophrenia. The neuroleptic therapy of schizophrenia, however, has been limited by tardive dyskinesia and by the relative inability of neuroleptics to ameliorate the negative symptoms of schizophrenia. Intensive research has been conducted to identify atypical neuroleptics which would not cause TD and which would have relatively greater efficacy in treating negative symptoms. Based upon animal models of TD and negative symptoms, four neuroleptics have been identified which may have these properties: clozapine, thioridazine, sulpiride, and molindone. Clinical studies of TD suggest that these four potentially atypical agents may have lower dyskinetic …

Zinc Supplementation As An Adjunct To Antibiotics In The Treatment Of Pneumonia In Children 2 To 59 Months Of Age, Batool A. Haider, Zohra S. Lassi, Amina Ahmed, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Diarrhoeal disorders and acute respiratory infections (ARIs), especially pneumonia, are the most common causes of death in low-income countries. Studies evaluating the impact of zinc supplementation as an adjunct in the management of pneumonia are limited and have shown variable results.
Objectives: To evaluate zinc supplementation, as an adjunct to antibiotics, in the treatment (clinical recovery) of pneumonia in children aged two to 59 months.
Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which contains the Cochrane Acute Respiratory Infections (ARI) Group's and the Cochrane Infectious Diseases Group's Specialised …

Infectious Disease As A Security Threat, With Particular Application To The Migration Context, Marielena Faria

Independent Study Project (ISP) Collection

This paper analyzes the threat infectious diseases impose on global security, specifically in the migration context. Infectious diseases can threaten security through a variety of areas, and this paper aims to identify the global spread of infectious diseases through migration, international crises, humanitarian emergencies, HIV/AIDS, and emerging and re-emerging infectious diseases. This paper explores global health, security, and migration in an attempt to determine if combining these three areas can be meaningful. Generally, studies approach only two of the three areas to examine a topic, but this paper will assess and point out when combining all three fields is relevant. …

The Effect Of Intermittent Umbilical Cord Occlusion On Elastin Composition In The Ovine Fetus., Jennifer A Thompson, Sarah A Gimbel, Bryan S Richardson, Robert Gagnon, Timothy Regnault

Paediatrics Publications

This study aimed to determine the effect of varying degrees of intermittent umbilical cord occlusion (UCO) on arterial elastin composition. Over 4 days, chronically catheterized late gestation fetal sheep received 5 total UCO per day lasting 1 min/h (mild group: n = 6), 2 min/h (moderate group: n = 4), 3 min/h (severe group; n = 6); or no occlusion (control group: n = 7). Each group was evaluated for elastin content of the carotid and superior mesenteric artery (SMA), the arterial pressure response to UCO, and plasma cortisol concentration. Elastin content of the carotid artery was significantly increased by …

Mechanisms Of Neuronal Death Induced By Environmental Toxicants In Murine Cortical Culture, Travis Rush

Dissertations (1934 -)

This study was directed at examining the neurotoxic mechanisms of several classes of environmental toxicants implicated in neurodegenerative disease. Primary cortical cultures were exposed to organophosphorus pesticides, heavy metals and the cyanobacterial toxin, beta-N-methylamino-L-alanine (BMAA). Several components relating to neuronal injury were assessed in each study and novel aspects are described.

The main action of organophosphorous insecticides is generally believed to be the inhibition of acetylcholinesterase. However, these compounds are now recognized to inhibit many other enzymes and cause neuronal death through a variety of mechanisms. I found that exposure to chlorpyrifos or diazinon caused concentration-dependent neurotoxicity that could not …

Smart Rehabilitation For The 21st Century: The Tampa Smart Home For Veterans With Traumatic Brain Injury, Jan Jasiewicz, William D. Kearns, Jeffrey Craighead, James L. Fozard, Steven Scott, Jay Mccarthy

Rehabilitation and Mental Health Counseling Faculty Publications

No abstract provided.

Alcoholic Cardiomyopathy: A Review., Anil George, Vincent M Figueredo

Division of Cardiology Faculty Papers

Alcohol abuse can cause cardiomyopathy indistinguishable from other types of dilated nonischemic cardiomyopathy. Most heavy drinkers remain asymptomatic in the earlier stages of disease progression, and many never develop the familiar clinical manifestations that typify heart failure. We review the current thinking on the pathophysiology, clinical characteristics, and treatments available for alcoholic cardiomyopathy. The relationship of alcohol to heart disease is complicated by the fact that in moderation, alcohol has been shown to afford a certain degree of protection against cardiovascular disease.

Systemic Adiponectin Malfunction As A Risk Factor For Cardiovascular Disease., Wayne Bond Lau, Ling Tao, Yajing Wang, Rong Li, Xin L Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad's metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad's anti-inflammatory …

Advanced Glycation End Products Accelerate Ischemia/Reperfusion Injury Through Receptor Of Advanced End Product/Nitrative Thioredoxin Inactivation In Cardiac Microvascular Endothelial Cells., Yi Liu, Yanzhuo Ma, Rutao Wang, Chenhai Xia, Rongqing Zhang, Kun Lian, Ronghua Luan, Lu Sun, Lu Yang, Wayne B Lau, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured …

Reduced Cardioprotective Action Of Adiponectin In High-Fat Diet-Induced Type Ii Diabetic Mice And Its Underlying Mechanisms., Wei Yi, Yang Sun, Erhe Gao, Xufeng Wei, Wayne Bond Lau, Qijun Zheng, Yajing Wang, Yuexing Yuan, Xiaoliang Wang, Ling Tao, Rong Li, Walter Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent …

Strain-Dependent Variation In The Early Transcriptional Response To Cns Injury Using A Cortical Explant System, David J. Graber, Brent T. Harris, William F. Hickey

Dartmouth Scholarship

While it is clear that inbred strains of mice have variations in immunological responsiveness, the influence of genetic background following tissue damage in the central nervous system is not fully understood. A cortical explant system was employed as a model for injury to determine whether the immediate transcriptional response to tissue resection revealed differences among three mouse strains. Immunological mRNAs were measured in cerebral cortex from SJL/J, C57BL/6J, and BALB/cJ mice using real time RT-PCR. Freshly isolated cortical tissue and cortical sections incubated in explant medium were examined. Levels of mRNA, normalized to β-actin, were compared using one way analysis …

In The Beginning...Phylogeny In Freud's Overview Of The Transference Neuroses: A Review-Essay, Emanuel E. Garcia, Md

Jefferson Journal of Psychiatry

A PHYLOGENETIC FANTASY

I. Grubrich-Simitis, editor

A. Hoffer and P. T. Hoffer, translators

Harvard University Press, Cambridge, Mass.

1987

Uses Of Carbamazepine For Psychiatric Disorders: A Review, Edward Kim, Md

Jefferson Journal of Psychiatry

Carbamazepine, first synthesized in 1953, was initially marketed in Europe as an anticonvulsant. In 1971 Dalby reported the drug's psychotropic effects, most notably mood stabilization, in patients with temporal lobe epilepsy (TLE) (1). Other psychiatric applications such as the treatment of affectively and behaviorally labile patients are being explored. These studies are yielding data relevant to the treatment and understanding of the neurobiology of mental illness. For this reason, familiarity with carbamazepine is becoming increasingly important to psychiatrists.

The Effect Of Acute And Chronic Ethanol On Dopamine Turnover In The Caudate Nucleus Of The Rat, Rif S. El-Mallakh, Md

Jefferson Journal of Psychiatry

It is generally believed that acute and chronic ethanol (EtOH) administration alters the activity of catecholamines in the brain, however, the specific effects of EtOH on the dopaminergic system are disputed (I). Acute EtOH administration has been variously reported to decrease (2,3), increase (4,5), and cause no change (6 ,7) in dopamine (DA) synthesis and turnover. Likewise, chronic EtOH treatments have been reported to decrease (2,8) and increase (9, 10) DA synthesis and turnover. Many of these apparently conflicting results are explained by the use of different animal models (rat (2, 3,6,7,10), rabbit (6), and mouse (4,5,9)), different methods of …

Book Review: The Soft Voice Of Reason, Emanuel E. Garcia, Md

Jefferson Journal of Psychiatry

FREUD AS AN EXPERT WITNESS

K. R. Eissler

Madison, Connecticut, International Universities Press 1986, 449 pages.

L-Deprenyl, A Selective Mao-B Inhibitor, Raymond W. Lam, Md

Jefferson Journal of Psychiatry

Monoamine oxidase inhibitors (MAOIs) are now recognized as effective medications in the treatment of major depression (1). However, their clinical use has been limited by the risk of severe hypertensive reactions to oral tyramine challenge. Prevention of this so-called "cheese effect " requires adherence to diet restrictions that can lead to problems with patient compliance to MAOIs.

L-deprenyl is a selective MAO-B inhibitor that is reportedly free of the "cheese effect" (2). This review will discuss the clinical and theoretical importance of this interesting drug.

Reciprocal Effects Of Oxidative Stress On Heme Oxygenase Expression And Activity Contributes To Reno-Vascular Abnormalities In Ec-Sod Knockout Mice, Tomoko Kawakami, Nitin Puri, Komal Sodhi, Lars Bellner, Toru Takahashi, Kiyoshi Morita, Rita Rezzani, Tim D. Oury, Nader G. Abraham

Biochemistry and Microbiology

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD^(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD^(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, …

Synthetic Heroin-Induced Parkinsonism, B.K. Gupta, Md

Jefferson Journal of Psychiatry

Parkinson's disease is a slowly progressive, neurodegenerative disorder affecting one in 1,000 of the general population; its incidence increases with age, but the cause remains unknown. The disease is characterized pathologically by a loss of neurons from the pigmented substantia nigra pars compacta, and a triad of physical symptoms of rigidity, tremor, and bradykinesia or akinesia . Thus the clinical condition of Parkinson's disease is a rather complex disorder with a variety of physical symptoms due to neuronal damage in a number of brain regions. Additional brain regions also affected in clinical Parkinson's disease include the ventral tegmental area, locus …

Treatment Of Mental Disorders In Pregnancy: A Review Of Neuroleptics, Antidepressants, And Lithium Carbonate, Lawrence L. Kerns, Md

Jefferson Journal of Psychiatry

Pregnancy is frequently complicated by the development or recurrence of a serious mental disorder; neurotic, major affective, and psychotic illnesses have all been observed (1-4). When a major mental disorder arises in a pregnant woman and threatens the health or life of the patient and/or fetus, it should be treated early and aggressively to minimize complications and forestall the advance of the disease. Nonbiologic methods like individual psychotherapy, couples or family therapy, social casework, and hospitalization in a supportive, structured milieu should form the first line of treatment. Electroconvulsive therapy (ECT) may be the treatment of choice for some patients, …

Diagnosis In The Neuroleptic Malignant Syndrome, James H. Dallman, Md, Cpt, Mc

Jefferson Journal of Psychiatry

Neuroleptic malignant syndrome (NMS) is an uncommon, potentially lethal complication of treatment with antipsychotic medication. First described in American journals by Delay and Deniker in 1968 (1), this syndrome has been reported for many years in the European and Japanese literature.

Carbamazepine In Treatment Of The Violent Psychotic Patient, Lauren A. Pate, Md

Jefferson Journal of Psychiatry

Violence in the psychiatric setting may be perpetrated by patients with a variety of diagnoses including character disorders, episodic dyscontrol syndromes, and drug or alcohol intoxication. The violent behavior of aggressive psychotic patients is typically the most bizarre, unpredictable, and the least responsive to intervention with neuroleptics or lithium carbonate. Carbamazepine, an established anticonvulsant, has achieved growing prominence as an adjunctive measure in treatment of the violent psychotic. This paper will review the literature and summarize the posited pharmacological mechanisms, reported side effects, and clinical experience with carbamazepine in controlling the symptoms of violence and aggression in psychosis.

The Stress Factor: Exploring The Possibility Of A Psychological Component To Cancer, Bernard M. Edelstein, Md

Jefferson Journal of Psychiatry

As dwellers in the same house, it seems only logical that psyche and soma would be interdependent , that well-being in one would promote health in the other, and that illness in one would soon become manifest in its partner. Yet quantifying this intuitive relationship has long been a difficult task. Establishing a mechanism for disease-heart disease, infectious disease, neoplastic disease which can withstand the scrutiny of experimental rigor, is difficult enough. To introduce a seemingly not quantifiable entity such as psychology in the form of stress or anxiety presents such great complexity that for a long time it seemed …

Psychoanalysis: Science Or Fiction?, Emanuel E. Garcia

Jefferson Journal of Psychiatry

The completion of this paper comes coincidentally at a time when a book by a scholarly philosopher, Adolf Grunbaum, entitled The Foundations of Psychoanalysis:A Philosophical Critique, has just been published and purports to answer the question of the scientific status of analysis. This temporally follows Jeffrey Masson's work (1) which accuses Freud of abandoning the so-called seduction hypothesis and by so doing laying unsound groundwork for the "science" that consumes Freud's nearly limitless energies . In short, it is a period in which psychoanalysis finds itself condemned, but perhaps in a …

Pipkiγ Regulates Focal Adhesion Dynamics And Colon Cancer Cell Invasion, Zhaofei Wu, Xiang Li, Manjula Sunkara, Heather Spearman, Andrew J. Morris, Cai Huang

Markey Cancer Center Faculty Publications

Focal adhesion assembly and disassembly are essential for cell migration and cancer invasion, but the detailed molecular mechanisms regulating these processes remain to be elucidated. Phosphatidylinositol phosphate kinase type Iγ (PIPKIγ) binds talin and is required for focal adhesion formation in EGF-stimulated cells, but its role in regulating focal adhesion dynamics and cancer invasion is poorly understood. We show here that overexpression of PIPKIγ promoted focal adhesion formation, whereas cells expressing either PIPKIγ^K188,200R or PIPKIγ^D316K, two kinase-dead mutants, had much fewer focal adhesions than those expressing WT PIPKIγ in CHO-K1 cells and HCT116 colon cancer cells. Furthermore, …

Activation Of Matrix Metalloproteinases Following Anti-Aβ Immunotherapy; Implications For Microhemorrhage Occurrence, Donna M. Wilcock, Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, Carol A. Colton

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur.

METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which …

Bioluminescent Imaging Reveals Divergent Viral Pathogenesis In Two Strains Of Stat1-Deficient Mice, And In Αßγ Interferon Receptor-Deficient Mice, Tracy Jo Pasieka, Lynne Collins, Megan A. O'Connor, Yufei Chen, Zachary M. Parker, Brent L. Berwin, David R. Piwnica-Worms, David A. Leib

Dartmouth Scholarship

Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factorsignal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat12/2 and IFNaßcR2/2 mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat12/2 mice and in IFNaßcR2/2 mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat12/2(N-term)) had transient infection of the liver and spleen, but succumbed to encephalitis by day …

Tropical Medicine: A Clinical Text, 8th Edition, Revised And Expanded, Kevin M. Cahill, M.D.

Institute of International Humanitarian Affairs

The history of tropical medicine is as dramatic as the story of humankind. It has its own myths and legends, including tales of epidemics that destroyed whole civilizations. Today, with silent stealth, tropical diseases still claim more lives than all the current wars combined. Having had the privilege of working throughout Africa, Asia, and Latin America, as well as in the great medical centers of Europe and the United States, the author presents the details essential for understanding pathogenesis, clinical manifestations, therapy, and prevention of the major tropical diseases. The text, now in its eighth edition, has been used for …