Physiology Commons^™

The Endogenous Molecular Clock Orchestrates The Temporal Separation Of Substrate Metabolism In Skeletal Muscle, Brian A. Hodge, Yuan Wen, Lance A. Riley, Xiping Zhang, Jonathan H. England, Brianna D. Harfmann, Elizabeth A. Schroder, Karyn A. Esser

Physiology Faculty Publications

BACKGROUND: Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. Within skeletal muscle exists an intrinsic molecular clock mechanism that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by …

Proteomic Analysis Of Media From Lung Cancer Cells Reveals Role Of 14-3-3 Proteins In Cachexia, Julie B. Mclean, Jennifer S. Moylan, Erin M. Wolf Horrell, Francisco H. Andrade

Physiology Faculty Publications

Aims: At the time of diagnosis, 60% of lung cancer patients present with cachexia, a severe wasting syndrome that increases morbidity and mortality. Tumors secrete multiple factors that contribute to cachectic muscle wasting, and not all of these factors have been identified. We used Orbitrap electrospray ionization mass spectrometry to identify novel cachexia-inducing candidates in media conditioned with Lewis lung carcinoma cells (LCM).

Results: One-hundred and 58 proteins were confirmed in three biological replicates. Thirty-three were identified as secreted proteins, including 14-3-3 proteins, which are highly conserved adaptor proteins known to have over 200 binding partners. We confirmed the …

Enhanced Nmda Receptor-Mediated Modulation Of Excitatory Neurotransmission In The Dorsal Vagal Complex Of Streptozotocin-Treated, Chronically Hyperglycemic Mice, Eva C. Bach, Katalin Cs. Halmos, Bret N. Smith

Physiology Faculty Publications

A variety of metabolic disorders, including complications experienced by diabetic patients, have been linked to altered neural activity in the dorsal vagal complex. This study tested the hypothesis that augmentation of N-Methyl-D-Aspartate (NMDA) receptor-mediated responses in the vagal complex contributes to increased glutamate release in the dorsal motor nucleus of the vagus nerve (DMV) in mice with streptozotocin-induced chronic hyperglycemia (i.e., hyperglycemic mice), a model of type 1 diabetes. Antagonism of NMDA receptors with AP-5 (100 μM) suppressed sEPSC frequency in vagal motor neurons recorded in vitro, confirming that constitutively active NMDA receptors regulate glutamate release in the DMV. There …

Determining The Role Of Il-4 Induced Neuroinflammation In Microglial Activity And Amyloid-Ss Using Bv2 Microglial Cells And App/Ps1 Transgenic Mice, Clare H. Latta, Tiffany L. Sudduth, Erica M. Weekman, Holly M. Brothers, Erin L. Abner, Gabriel J. Popa, Michael D. Mendenhall, Floracita Gonzalez-Oregon, Kaitlyn Braun, Donna M. Wilcock

Physiology Faculty Publications

Background

Microglia are considered the resident immune cells of the central nervous system (CNS). In response to harmful stimuli, an inflammatory reaction ensues in which microglia are activated in a sequenced spectrum of pro- and antiinflammatory phenotypes that are akin to the well-characterized polarization states of peripheral macrophages. A “classically” activated M1 phenotype is known to eradicate toxicity. The transition to an “alternatively” activated M2 phenotype encompasses neuroprotection and repair. In recent years, inflammation has been considered an accompanying pathology in response to the accumulation of extracellular amyloid-β (Aβ) in Alzheimer’s disease (AD). This study aimed to drive an M2a-biased …

Smooth-Muscle Bmal1 Participates In Blood Pressure Circadian Rhythm Regulation, Zhongwen Xie, Wen Su, Shu Liu, Guogang Zhao, Karyn Esser, Elizabeth A. Schroder, Mellani Lefta, Harald M. Stauss, Zhenheng Guo, Ming Cui Gong

Physiology Faculty Publications

As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood …

Mitochondria Dysfunction In Lung Cancer-Induced Muscle Wasting In C2c12 Myotubes, Julie B. Mclean, Jennifer S. Moylan, Francisco H. Andrade

Physiology Faculty Publications

Aims: Cancer cachexia is a syndrome which results in severe loss of muscle mass and marked fatigue. Conditioned media from cachexia-inducing cancer cells triggers metabolic dysfunction in skeletal muscle, including decreased mitochondrial respiration, which may contribute to fatigue. We hypothesized that Lewis lung carcinoma conditioned medium (LCM) would impair the mitochondrial electron transport chain (ETC) and increase production of reactive oxygen species, ultimately leading to decreased mitochondrial respiration. We incubated C2C12 myotubes with LCM for 30 min, 2, 4, 24 or 48 h. We measured protein content by western blot; oxidant production by 2′,7′-dichlorofluorescin diacetate (DCF), 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF), and …

In Vivo Identification Of Eugenol-Responsive And Muscone-Responsive Mouse Odorant Receptors, Timothy S. Mcclintock, Kaylin Adipietro, William B. Titlow, Patrick Breheny, Andreas Walz, Peter Mombaerts, Hiroaki Matsunami

Physiology Faculty Publications

Our understanding of mammalian olfactory coding has been impeded by the paucity of information about the odorant receptors (ORs) that respond to a given odorant ligand in awake, freely behaving animals. Identifying the ORs that respond in vivo to a given odorant ligand from among the ∼1100 ORs in mice is intrinsically challenging but critical for our understanding of olfactory coding at the periphery. Here, we report an in vivo assay that is based on a novel gene-targeted mouse strain, S100a5-tauGFP, in which a fluorescent reporter selectively marks olfactory sensory neurons that have been activated recently in vivo. Because each …

Cannabinoid Receptor 2 Agonist Attenuates Pain Related Behavior In Rats With Chronic Alcohol/High Fat Diet Induced Pancreatitis, Liping Zhang, Robert H. Kline Iv, Terry A. Mcnearney, Michael P. Johnson, Karin Westlund High

Physiology Faculty Publications

BACKGROUND: Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in …

Longitudinal Trajectories Of Cholesterol From Midlife Through Late Life According To Apolipoprotein E Allele Status, Brian Downer, Steven Estus, Yuriko Katsumata, David W. Fardo

Physiology Faculty Publications

Background: Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE), a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life.

Methods: Cholesterol trajectories from midlife through late life were modeled using generalized …

An Intronic Picalm Polymorphism, Rs588076, Is Associated With Allelic Expression Of A Picalm Isoform, Ishita Parikh, Christopher Medway, Steven Younkin, David Fardo, Steven Estus

Physiology Faculty Publications

BACKGROUND: Although genome wide studies have associated single nucleotide polymorphisms (SNP)s near PICALM with Alzheimer's disease (AD), the mechanism underlying this association is unclear. PICALM is involved in clathrin-mediated endocytosis and modulates Aß clearance in vitro. Comparing allelic expression provides the means to detect cis-acting regulatory polymorphisms. Thus, we evaluated whether PICALM showed allele expression imbalance (AEI) and whether this imbalance was associated with the AD-associated polymorphism, rs3851179.

RESULTS: We measured PICALM allelic expression in 42 human brain samples by using next-generation sequencing. Overall, PICALM demonstrated equal allelic expression with no detectable influence by rs3851179. A single sample demonstrated …

Neutral Sphingomyelinase-3 Mediates Tnf-Stimulated Oxidant Activity In Skeletal Muscle, Jennifer S. Moylan, Jeffrey D. Smith, Erin M. Wolf Horrell, Julie B. Mclean, Gergana M. Deevska, Mark R. Bonnell, Mariana N. Nikolova‑Karakashian, Michael B. Reid

Physiology Faculty Publications

AIMS: Sphingolipid and oxidant signaling affect glucose uptake, atrophy, and force production of skeletal muscle similarly and both are stimulated by tumor necrosis factor (TNF), suggesting a connection between systems. Sphingolipid signaling is initiated by neutral sphingomyelinase (nSMase), a family of agonist-activated effector enzymes. Northern blot analyses suggest that nSMase3 may be a striated muscle-specific nSMase. The present study tested the hypothesis that nSMase3 protein is expressed in skeletal muscle and functions to regulate TNF-stimulated oxidant production.

RESULTS: We demonstrate constitutive nSMase activity in skeletal muscles of healthy mice and humans and in differentiated C2C12 myotubes. nSMase3 ( …

Arrhythmogenic Calmodulin Mutations Disrupt Intracellular Cardiomyocyte Ca2+ Regulation By Distinct Mechanisms, Guo Yin, Faisal Hassan, Ayman R. Haroun, Lisa L. Murphy, Lia Crotti, Peter J. Schwartz, Alfred L. George, Jonathan Satin

Physiology Faculty Publications

BACKGROUND: Calmodulin (CaM) mutations have been identified recently in subjects with congenital long QT syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT), but the mechanisms responsible for these divergent arrhythmia-susceptibility syndromes in this context are unknown. We tested the hypothesis that LQTS-associated CaM mutants disrupt Ca²⁺ homeostasis in developing cardiomyocytes possibly by affecting either late Na current or Ca²⁺-dependent inactivation of L-type Ca²⁺ current.

METHODS AND RESULTS: We coexpressed CaM mutants with the human cardiac Na channel (Na_V1.5) in tsA201 cells, and we used mammalian fetal ventricular cardiomyocytes to investigate LQTS- and CPVT-associated CaM …

Combination Therapy Of Hyaluronic Acid Mesotherapic Injections And Sclerotherapy For Treatment Of Lower Leg Telangiectasia Without Major Venous Insufficiency: A Preliminary Clinical Study, Tommaso Iannitti, Valentina Rottigni, Federica Torricelli, Beniamino Palmieri

Physiology Faculty Publications

Background. Telangiectasia is the dilation of dermal capillaries mainly due to hypertension and vein insufficiency. Treatments of choice for this condition are sclerotherapy with foam liquid or intradermal fiber optic laser energy delivery. Aim. The aim of this study was to assess the efficacy of a new therapeutic approach consisting in the use of polymerized hyaluronic acid mesotherapicinjections following sclerotherapy in the areas of the skin affected by telangiectasia in patients without major vein insufficiency. Materials and Methods. A total of 20 women, aged between 19 and 64 years, affected by recurrent lower leg telangiectasia, were included in this study. …

Sex Differences In A Mouse Model Of Multiple Sclerosis: Neuropathic Pain Behavior In Females But Not Males And Protection From Neurological Deficits During Proestrus, Elizabeth J. Rahn, Tommaso Iannitti, Renee R. Donahue, Bradley K. Taylor

Physiology Faculty Publications

BACKGROUND: Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is one of the most prevalent neurological disorders in the industrialized world. This disease afflicts more than two million people worldwide, over two thirds of which are women. MS is typically diagnosed between the ages of 20-40 and can produce debilitating neurological impairments including muscle spasticity, muscle paralysis, and chronic pain. Despite the large sex disparity in MS prevalence, clinical and basic research investigations of how sex and estrous cycle impact development, duration, and severity of neurological impairments and pain symptoms are limited. To help address these questions, …

Β-Amyloid Deposition Is Shifted To The Vasculature And Memory Impairment Is Exacerbated When Hyperhomocysteinemia Is Induced In App/Ps1 Transgenic Mice, Tiffany L. Sudduth, Erica M. Weekman, Holly M. Brothers, Kaitlyn Braun, Donna M. Wilcock

Physiology Faculty Publications

INTRODUCTION: Vascular dementia is the second most common cause of dementia after Alzheimer's disease (AD). In addition, it is estimated that almost half of all AD patients have significant cerebrovascular disease comorbid with their AD pathology. We hypothesized that cerebrovascular disease significantly impacts AD pathological progression.

METHODS: We used a dietary model of cerebrovascular disease that relies on the induction of hyperhomocysteinemia (HHcy). HHcy is a significant clinical risk factor for stroke, cardiovascular disease and type 2 diabetes. In the present study, we induced HHcy in APP/PS1 transgenic mice.

RESULTS: While total β-amyloid (Aβ) load is unchanged across groups, Congophilic …

Analgesic Tolerance Of Opioid Agonists In Mutant Mu-Opioid Receptors Expressed In Sensory Neurons Following Intrathecal Plasmid Gene Delivery, Guangwen Li, Fei Ma, Yanping Gu, Li-Yen Mae Huang

Physiology Faculty Publications

Background: Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs) are known to play critical roles in the receptor functions. Our understanding of their participation in opioid analgesia is mostly based on studies of opioid effects on mutant receptors expressed in in vitro preparations, including cell lines, isolated neurons and brain slices. The behavioral consequences of the mutation have not been fully explored due to the complexity in studies of mutant receptors in vivo. To facilitate the determination of the contribution of phosphorylation sites in MOR to opioid-induced analgesic behaviors, we expressed mutant and wild-type human MORs (hMORs) in sensory …

Molecular Events In The Cell Types Of The Olfactory Epithelium During Adult Neurogenesis, Paula M. Heron, Arnold J. Stromberg, Patrick Breheny, Timothy S. Mcclintock

Physiology Faculty Publications

BACKGROUND: Adult neurogenesis, fundamental for cellular homeostasis in the mammalian olfactory epithelium, requires major shifts in gene expression to produce mature olfactory sensory neurons (OSNs) from multipotent progenitor cells. To understand these dynamic events requires identifying not only the genes involved but also the cell types that express each gene. Only then can the interrelationships of the encoded proteins reveal the sequences of molecular events that control the plasticity of the adult olfactory epithelium.

RESULTS: Of 4,057 differentially abundant mRNAs at 5 days after lesion-induced OSN replacement in adult mice, 2,334 were decreased mRNAs expressed by mature OSNs. Of the …

Tricellulin Deficiency Affects Tight Junction Architecture And Cochlear Hair Cells, Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin

Physiology Faculty Publications

The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while …

Mouse Strain Determines Cardiac Growth Potential, Carmen Kiper, Barry Grimes, Gary Van Zant, Jonathan Satin

Physiology Faculty Publications

RATIONALE: The extent of heart disease varies from person to person, suggesting that genetic background is important in pathology. Genetic background is also important when selecting appropriate mouse models to study heart disease. This study examines heart growth as a function of strain, specifically C57BL/6 and DBA/2 mouse strains.

OBJECTIVE: In this study, we test the hypothesis that two strains of mice, C57BL/6 and DBA/2, will produce varying degrees of heart growth in both physiological and pathological settings.

METHODS AND RESULTS: Differences in heart dimensions are detectable by echocardiography at 8 weeks of age. Percentages of cardiac progenitor cells (c-kit+ …

Dexamethasone Rapidly Increases Gaba Release In The Dorsal Motor Nucleus Of The Vagus Via Retrograde Messenger-Mediated Enhancement Of Trpv1 Activity, Andrei V. Derbenev, Bret N. Smith

Physiology Faculty Publications

Glucocorticoids influence vagal parasympathetic output to the viscera via mechanisms that include modulation of neural circuitry in the dorsal vagal complex, a principal autonomic regulatory center. Glucocorticoids can modulate synaptic neurotransmitter release elsewhere in the brain by inducing release of retrograde signalling molecules. We tested the hypothesis that the glucocorticoid agonist dexamethasone (DEX) modulates GABA release in the rat dorsal motor nucleus of the vagus (DMV). Whole-cell patch-clamp recordings revealed that DEX (1-10 µM) rapidly (i.e. within three minutes) increased the frequency of tetrodotoxin-resistant, miniature IPSCs (mIPSCs) in 67% of DMV neurons recorded in acutely prepared slices. Glutamate-mediated mEPSCs were …

Down's Syndrome, Neroinflammation, And Alzheimer Neuropathogenesis, Donna M. Wilcock, W. Sue T. Griffin

Physiology Faculty Publications

Down syndrome (DS) is the result of triplication of chromosome 21 (trisomy 21) and is the prevailing cause of mental retardation. In addition to the mental deficiencies and physical anomalies noted at birth, triplication of chromosome 21 gene products results in the neuropathological and cognitive changes of Alzheimer's disease (AD). Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that this chromosome 21 gene product was a principal neuropathogenic culprit in AD as well as DS. The discovery of …

Voluntary Exercise Protects Against Methamphetamine-Induced Oxidative Stress In Brain Microvasculature And Disruption Of The Blood--Brain Barrier, Michal Toborek, Melissa J. Seelbach, Cetewayo S. Rashid, Ibolya E. András, Lei Chen, Minseon Park, Karyn A. Esser

Physiology Faculty Publications

BACKGROUND: There is no effective therapeutic intervention developed targeting cerebrovascular toxicity of drugs of abuse, including methamphetamine (METH). We hypothesize that exercise protects against METH-induced disruption of the blood--brain barrier (BBB) by enhancing the antioxidant capacity of cerebral microvessels and modulating caveolae-associated signaling. Mice were subjected to voluntary wheel running for 5 weeks resembling the voluntary pattern of human exercise, followed by injection with METH (10 mg/kg). The frequency, duration, and intensity of each running session were monitored for each mouse via a direct data link to a computer and the running data are analyzed by Clock labTM Analysis software. …

Neural Circuit Mechanisms Of Post-Traumatic Epilepsy, Robert F. Hunt, Jeffery A. Boychuk, Bret N. Smith

Physiology Faculty Publications

Traumatic brain injury (TBI) greatly increases the risk for a number of mental health problems and is one of the most common causes of medically intractable epilepsy in humans. Several models of TBI have been developed to investigate the relationship between trauma, seizures, and epilepsy-related changes in neural circuit function. These studies have shown that the brain initiates immediate neuronal and glial responses following an injury, usually leading to significant cell loss in areas of the injured brain. Over time, long-term changes in the organization of neural circuits, particularly in neocortex and hippocampus, lead to an imbalance between excitatory and …

Molecular Remodeling Of Tip Links Underlies Mechanosensory Regeneration In Auditory Hair Cells, Artur A. Indzhykulian, Ruben Stepanyan, Anastasiia Nelina, Kateri J. Spinelli, Zubair M. Ahmed, Inna A. Belyantseva, Thomas B. Friedman, Peter G. Barr-Gillespie, Gregory I. Frolenkov

Physiology Faculty Publications

Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at the upper end of the link. In terminally differentiated mammalian auditory hair cells, tip links are subjected to sound-induced forces throughout an organism's life. Although hair cells can regenerate disrupted tip links and restore hearing, the molecular details of this process are unknown. We developed a novel implementation of backscatter electron scanning microscopy to visualize simultaneously …

Does Naloxone Reinstate Secondary Hyperalgesia In Humans After Resolution Of A Burn Injury? A Placebo-Controlled, Double-Blind, Randomized, Cross-Over Study, Manuel P. Pereira, Mads U. Werner, Thomas K. Ringsted, Michael C. Rowbotham, Bradley K. Taylor, Joergen B. Dahl

Physiology Faculty Publications

INTRODUCTION: Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain, have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists. In the present study in humans, we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury.

METHODS: Twenty-two healthy volunteers were included in this placebo-controlled, randomized, double-blind, cross-over study. Following baseline assessment of thermal and mechanical thresholds, a first-degree burn injury …

Summary Of Papers Presented At The 2012 Seventh International Cough Symposium, Peter V. Dicpinigaitis, Giovanni A. Fontana, Lu-Yuan Lee, Milos Tatar

Physiology Faculty Publications

Twenty six papers were presented as posters in the Seventh International Symposium on Cough; 12 papers were presented in the Basic Science of Cough session, and 14 papers presented in the Clinical Science of Cough session. These papers explored a wide spectrum of cough-related areas including pathophysiological mechanisms, treatment and detection of cough, and symptom assessment and perception, and were grouped into several general themes for facilitate the discussion. Studies presented in these posters have provided new information that should improve our knowledge on the basic physiology and pharmacology of cough, and the peripheral and central neural mechanisms involved in …

Derivation Of Multivariate Syndromic Outcome Metrics For Consistent Testing Across Multiple Models Of Cervical Spinal Cord Injury In Rats, Adam R. Ferguson, Karen-Amanda Irvine, John C. Gensel, Jessica L. Nielson, Amity Lin, Johnathan Ly, Mark R. Segal, Rajiv R. Ratan, Jacqueline C. Bresnahan, Michael S. Beattie

Physiology Faculty Publications

Spinal cord injury (SCI) and other neurological disorders involve complex biological and functional changes. Well-characterized preclinical models provide a powerful tool for understanding mechanisms of disease; however managing information produced by experimental models represents a significant challenge for translating findings across research projects and presents a substantial hurdle for translation of novel therapies to humans. In the present work we demonstrate a novel 'syndromic' information-processing approach for capitalizing on heterogeneous data from diverse preclinical models of SCI to discover translational outcomes for therapeutic testing. We first built a large, detailed repository of preclinical outcome data from 10 years of basic …

Excitatory Amino Acids Display Compartmental Disparity Between Plasma And Synovial Fluid In Clinical Arthropathies, Terry A. Mcnearney, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Previous studies have demonstrated elevated levels of excitatory amino acids (EAA) glutamate (Glu) and aspartate (Asp) in the synovial fluid (SF) of patients with active arthritis. The source of SF EAA concentrations are thought in large part to be secondary to passive diffusion from the plasma across synovial membranes and less so, reflective of local synovial pathology.

OBJECTIVE: This descriptive report assesses the hypothesis that the SF EAA levels reflect inflammatory processes of the joint and are not dependent on plasma levels.

METHODS: Simultaneously drawn plasma and SF samples were obtained from 14 recently deceased cadavers and 10 patients …

The Feasibility Of A Fiber Optic Laser Approach To Relieving Lymphedematous Syndrome: A Case Report, Beniamino Palmieri, Alessandro Di Cerbo, Valentina Rottigni, Gregorio Fistetto, Tommaso Iannitti

Physiology Faculty Publications

Here we report a case of successful fiber optic laser treatment of lymphedema in a swollen arm post mastectomy. At the moment, this procedure has only anecdotal evidence to justify its use, but in our experience is a feasible, minimally invasive day-stay procedure which has been demonstrated to be safe and effective. Further nonhomogeneous case pooling and follow-up would enable guidelines and definite surgical protocols for its use to be implemented.

Rapid Glucocorticoid-Induced Activation Of Trp And Cb1 Receptors Causes Biphasic Modulation Of Glutamate Release In Gastric-Related Hypothalamic Preautonomic Neurons, Carie R. Boychuk, Andrea Zsombok, Jeffrey G. Tasker, Bret N. Smith

Physiology Faculty Publications

Glucocorticoids rapidly regulate synaptic input to neuroendocrine cells in the hypothalamic paraventricular nucleus (PVN) by inducing the retrograde release of endogenous messengers. Here we investigated the rapid effects of dexamethasone (DEX) on excitatory synaptic input to feeding-related, preautonomic PVN neurons using whole-cell patch-clamp recordings. In ∼50% of identified gastric-related preautonomic PVN neurons, DEX elicited a biphasic synaptic response characterized by an initial rapid and transient increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), followed by a decrease in mEPSC frequency within 9 min; remaining cells displayed only a decrease in mEPSC frequency. The late-phase decrease in mEPSC frequency …