Medicine and Health Sciences Commons^™

A Computational Model Of Multiple Interconnected Capillary Modules In Skeletal Muscle, Raashi Vijay

Electronic Thesis and Dissertation Repository

Background: Skeletal muscle (SM), with its precise O₂ supply-demand matching, is ideal for studying microvascular (MV) function, which is crucial in cardiovascular physiology and disease. Our goal is to gain understanding of SM microcirculation using recent capillary network module (CM) data from rat in a computational model.

Methods: We construct a 4-CM network, with single-vessel equivalents for each CM, three arterioles, and two venules. A two-phase (plasma/RBCs) steady-state model is used to calculate blood flow. An iterative boundary pressure finding method is developed to match flow in CMs.

Results: We validate our flow and pressure models …

Endothelial Dysfunction In Hindlimb Arteries Of Old Sprague Dawley Rats, And The Type 2 Diabetic Zucker Diabetic Sprague Dawley Strain., Andrea N. Wang

Electronic Thesis and Dissertation Repository

Ageing, and type 2 diabetes are associated with cardiovascular diseases and endothelial dysfunction. Endothelial dysfunction is characterized by a decline in endothelium-mediated vasodilation. In this thesis, we determined the vascular function of hindlimb arteries supplying skeletal muscle and extremities using isolated arteries and wire myography. For ageing studies, we used Sprague Dawley rats and for type 2 diabetes we used the Zucker Diabetic Sprague Dawley strain. Vasodilation of hindlimb arteries with acetylcholine were impaired in both models. However, protease-activated receptor 2 mediated vasodilation was upregulated in arteries. Evidence of non-nitric oxide mechanisms were also found in peripheral vasculature. These data …

Malignant Hyperthermia, Courtney Morris

Nursing Student Class Projects (Formerly MSN)

Malignant Hyperthermia as defined by the International Classification of Diseases is a rare but progressive, and life-threatening hyperthermic reaction in response to a triggering agent such as general anesthetic gases or the depolarizing neuromuscular blocking agent Succinylcholine (Hopkins et. al., 2020). MalignantHyperthymia is a genetic disorder of the skeletal muscle, that leads to continuous muscle contraction and the inability to relax skeletal muscle (Haili and Weant, 2021). Signs and symptoms can vary from patient to patient and can be masked by anesthesia, but the classical signs include an increase in end-tidal CO2, increased heart rate, and a rapid increase in …

Hyperphosphatemia Contributes To Functional Iron Deficiency And Skeletal Muscle Wasting, Brian Anthony Czaya

All ETDs from UAB

Chronic kidney disease (CKD) is a global health threat that increases risk of death, which is credible to both impaired renal function and a multitude of CKD- associated comorbidities such as systemic inflammation, anemia and skeletal muscle dys- function. A distinctive feature of CKD is the dysregulation of mineral metabolism, where excess serum levels of phosphate (hyperphosphatemia) and of fibroblast growth factor 23 (FGF23) are not only viewed as biomarkers for disease severity but also exert deleterious effects towards various CKD-associated pathologies. Elevated levels of FGF23 can lead to the activation of FGF receptor 4 (FGFR4) in cell types that …

The Comparison Of Endothelial Permeability At 48 Hours Post Skeletal Muscle Injury In Male And Female Mice At Various Ages, Sabrina Tusavitz

Health and Exercise Physiology Honors Papers

We compared endothelial permeability at 48 hours post skeletal muscle injury in male and female mice at 1 month, 2 months, 3, 6 and 12 months of age. We hypothesized that the female mice would show more permeability at 48 hours post injury than the male mice at all ages. Our findings were more complicated as permeability following injury trends down with age in females, and up with age in males. These findings could be beneficial for medical professionals to tailor an injured athlete’s treatment to their age and sex since there are permeability and therefore possibly inflammation differences.

Examining Permeability And Contractility Of Skeletal Muscle In Castrated Male Mice, Evan Scott

Health and Exercise Physiology Honors Papers

A common method of treating skeletal muscle injury is temperature therapy. Temperature affects one of the initial aspects of skeletal muscle healing, the increasing of vascular permeability. Previous data accumulated from the Ursinus College Skeletal Muscle Lab suggests that vascular permeability following temperature therapy is different between the anatomically intact male and female mice. However, there have not been any studies to date that are able determine the cause of these permeability differences following temperature treatment. In addition, it is currently unclear how increased vascular permeability affects skeletal muscle healing. A possible cause for these differences is the increased presence …

Submaximal Isometric Force Steadiness In People With Multiple Sclerosis Under Single And Dual Task Conditions, Sheri Bunyan

Dissertations (1934 -)

Activities of daily living require steady, non-fatiguing, isometric muscular contractions to maintain postural control and stabilize body segments to facilitate interaction with the environment. Furthermore, typical activities often require simultaneous performance of cognitive and motor tasks. This may challenge people with multiple sclerosis, a chronic neurodegenerative disease of the central nervous system associated with motor and cognitive impairments. Despite functional relevance, isometric force steadiness in both the upper and lower extremities has not been explored in this population. Additionally, dual task experiments in multiple sclerosis have primarily used gait, a dynamic activity, as the motor task. Thus, the purpose of …

Role Of Atp1a1 In Skeletal Muscle Growth And Metabolism, Laura C. Kutz

Theses, Dissertations and Capstones

Skeletal muscle comprises approximately 30% of total body mass, and loss of muscle mass and dysfunctional muscle metabolism are implicated in multiple disease states, including type 2 diabetes, heart failure, and septic shock. As such, understanding the mechanisms of skeletal muscle growth and atrophy, including pharmaceutical targets that may prove safe and effective, is therefore an important goal of current research on skeletal muscle physiology. One potential target in skeletal muscle development and function that has not been fully explored is the Na/KATPase (NKA), especially the α1 isoform. This isoform has a unique signaling function that has previously been shown …

Microvascular Stenosis In Critical Limb Ischemia: Role Of Partial Endothelial To Mesenchymal Transition, Jacqueline M. Chevalier

Electronic Thesis and Dissertation Repository

Critical limb ischemia (CLI) is a widespread and debilitating manifestation of atherosclerosis. Unfortunately, revascularization strategies are often precluded or unsuccessful, resulting in amputation. A major reason for treatment failure is likely co-existing abnormalities in ­­the microvasculature. However, the specific microvascular defects present in end-stage PAD in humans remain unknown.

The purpose of this study was to delineate abnormalities in the microvascular wall in the critically ischemic skeletal muscle of patients with CLI.

To elucidate the microvascular landscape in CLI, we studied human tibialis anterior and gastrocnemius muscles harvested from below-knee amputations of 10 individuals with CLI. Control muscles are from …

Association Of Skeletal Muscle And Psychological Responses To Immobility After Major Injury, Jacob T. Higgins

Theses and Dissertations--Nursing

The purpose of this dissertation was to explore the physical and psychological responses to the combination of major trauma (Injury Severity Score [ISS] > 15) and variable periods of immobility. Specific aims were to: 1) develop a conceptual model that illustrates physiological and psychological alterations that occur after injury and subsequent immobility, and their association with skeletal muscle responses and recovery; 2) evaluate daily measures of skeletal muscle strength (bicep and quadricep) using dynamometry and skeletal muscle (rectus femoris and biceps brachii) muscle thickness measured with ultrasound in patients after major trauma; and 3) assess the predictive ability of anxiety and …

An Integrated Approach To Analyzing Arteriolar Network Hemodynamics., Zahra Farid

Electronic Thesis and Dissertation Repository

The objective of this thesis was to optimize our technique for studying blood flow in arteriolar networks by including capillary resistance and venular network geometry. We aimed to validate our technique using experimental flow measurements and Murray’s law. First, arteriolar and venular networks were reconstructed from intravital videomicroscopy (IVVM) images of the gluteus maximus muscle, and capillary resistance was estimated and distributed to each terminal arteriole (TA) segment according to its diameter. Resistance for small arterioles and venules that were likely missed in our IVVM experiments were also added to each TA segment in our reconstructed networks based on measured …

Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert

Electronic Theses and Dissertations

Skeletal muscle mass, contractile properties, and metabolic function are regulated through the coordinated activation of multiple intracellular signaling pathways and genetic reprogramming. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many cell types, including skeletal muscle. Disruption of calcium levels or accumulation of misfolded proteins in the ER lumen leads to stress, which results in the activation of a signaling network called the unfolded protein response (UPR). Further, recent studies have suggested that in certain conditions, UPR pathways can be activated independent of ER stress. However, the role of ER stress and the …

Comparison Of Muscle Physiology And Performance Outcomes From Either Relative Intensity Or Repetition Maximum Training, Kevin Carroll

Electronic Theses and Dissertations

The main purpose of this dissertation was to compare performance and physiological outcomes of between a repetition maximum (RM) and a relative intensity using sets-and-repetitions (RI_SR) resistance training (RT) program in well-trained lifters. Fifteen subjects underwent RT 3 d·wk^-1 for 10-weeks in either a RM group (n=8) or RI_SR group (n=7). The RM group achieved a relative maximum each day while the RI_SR group trained based on percentages. Testing included percutaneous needle biopsies of the vastus lateralis, ultrasonography, unweighted (g to assess within and between-group alterations. RI_SR from pre-to-post yielded statistically significant increases in …

Characterization Of The Roles Of Muscle-Synthesized Brain-Derived Neurotrophic Factor And Presynaptic Tyrosine Receptor Kinase B In Motor Neuron Axonal Transport, Luke A. Vanosdol

All NMU Master's Theses

Brain-derived neurotrophic factor (BDNF) is a small, diffusible protein essential for the development and function of neurons. It is synthesized by many types of tissue, including muscle. BDNF actions are mediated via binding to its receptor, tyrosine receptor kinase B (TrkB). The BDNF-TrkB complex is endocytosed into a specialized vesicle, which induces downstream signaling cascades locally in the dendrites, or, more often, is delivered to the cell soma via retrograde axonal transport, where it modulates gene expression. BDNF activation of TrkB is critical for the initiation of axonal transport, and this cellular process relies on the interaction of numerous adaptor …

Angiogenesis And Neo-Microcirculatory Function In Diseased Tissue Revealed By Intravital Microscopy, Giovanni-Michele Arpino

Electronic Thesis and Dissertation Repository

Angiogenesis is the process of generating new blood microvessels. In adults, angiogenesis is fundamental to tumor biology and also to tissues rendered ischemic from vascular occlusion. Despite a promising appeal, strategies designed to simulate or otherwise modify the angiogenic process in adult tissues have yet to realize significant therapeutic potential. Importantly, understanding the structure and function of new microvascular networks formed in adult, diseased tissues is limited. In fact, it remains unknown if a new or regenerated microcirculation can effectively deliver oxygen to the tissue. The purpose of this thesis was to seek out novel determinants of functional angiogenesis and …

The Effect Of Insulin Treatment And Exercise Modality On Skeletal Muscle Fiber Size In Streptozotocin-Induced Type 1 Diabetic Rats, John Z. Nickels

Electronic Thesis and Dissertation Repository

Severe Type 1 Diabetes Mellitus (T1DM) is known to have several negative effects on skeletal muscle mass, a condition known as diabetic myopathy. One of these effects is the atrophy of the glycolytic muscle fibers. However, the role of intensity of insulin treatment and exercise modality in attenuating this loss in fiber cross-sectional area (CSA) specifically has yet to be determined. The purpose of this investigation was to determine the effects of 12 weeks of differing intensity of insulin therapy and exercise modality on the CSA of plantaris muscle fibers, identified by myosin heavy chain (MHC) of STZ-induced T1DM rats. …

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …

Prescription Strength Ibuprofen Interferes With Prophylactic Adaptations To Heavy Exercise, Jessica Ehrbar

Masters Theses, 2010-2019

Purpose: This proof of concept study was designed to assess the influence of prescription-strength Ibuprofen (IBU) on the repeated bout effect (RBE) of heavy exercise. METHODS: Eight males (23 ± 4 yrs) with no recent history of lower-body resistance training completed two separate testing phases separated by a seven-day washout period. Each phase consisted of two sessions of single-legged resistance exercise (RE), performed on the same leg, separated by ten days. One RE trial included 10 sets of 10 repetitions of maximal unilateral eccentric leg extensions at 120% 1RM. Each phase was characterized by a distinct treatment of either 800mg …

Systemic Insulin Sensitivity And Skeletal Muscle Akt Signaling In Rats Artificially Selected For Low And High Aerobic Capacity, Kyle Levi Fulghum

MSU Graduate Theses

The mechanism(s) linking physical inactivity, obesity, and type-II diabetes are unclear. I hypothesized low intrinsic aerobic capacity is associated with reduced systemic insulin sensitivity via skeletal muscle insulin signaling. After 34 generations of selective breeding, high aerobic capacity (HCR) rats exhibited an 8-fold increase in running distance vs low aerobic capacity (LCR) rats (n=14 per group). LCR rats had higher rates of weight gain vs HCR (p<0.05) though food consumption was constant (p=0.86) over a 12-week study. Rats were divided into 4 groups: 1) LCR-Sham Surgery, 2) LCR-Catheterization, 3) HCR-Sham Surgery or 4) HCR-Catheterization (n=7 per group). Euglycemic-hyperinsulinemic clamps on catheterized rats tested insulin sensitivity while sham LCR and HCR were used for basal tissue analysis. Plasma insulin levels did not differ during the clamps, but LCR required lower glucose infusion rates than HCR (p<0.05). Upon insulin stimulation, both absolute and normalized phospho-Akt(Ser473) of soleus muscle were significantly increased in HCR above basal group (p<0.05), but not in LCR. No difference was observed between insulin-stimulated phospho-Akt(Ser473) of HCR and LCR groups . These data support that LCR is linked to a reduction in insulin sensitivity in vivo without impairments of insulin-stimulated skeletal muscle phospho-Akt(Ser473) vs HCR rats.

Molecular Mechanisms Underlying The Muscle Response To Exercise-Induced Muscle Damage In Chronic Cigarette Smokers, Nina Moore

Doctoral Dissertations

Smoking increases risk for musculoskeletal injury and protracts healing. The underlying mechanisms have not been explored, yet dysregulated inflammatory responses may contribute. To investigate these risks, Study 1 of this dissertation monitored typical responses to muscle damaging eccentric contractions (ECC) in smokers and nonsmokers. Smokers experienced greater muscle fatigue both during and immediately after ECC and greater delayed hyperalgesia, a phenomenon known as delayed onset muscle soreness (DOMS), than did non-smokers. DOMS (driven by inflammation) peaks 48h after ECC, when there is a shift from pro- to anti-inflammatory signaling; thus I chose to investigate this time further in smokers. The …

Identifying The Molecular Mechanisms Of Early Cachexia Using Whole Transcriptome Sequencing In Muscle And Fat Biopsies From Cancer Patients, Amal Hussain Al Hadad

Dissertations

Cancer cachexia is responsible for one third of cancer–related deaths and contributes to the death of many others. More than 80% of cancer patients are cachectic towards the end of life. Despite intensive research, the mechanisms of cancer cachexia are still poorly understood. It is our hypothesis that identification of early changes in gene expression in cachexia will lead to an improved understanding of the mechanism that trigger this important problem in cancer patients. Thus, to shed light on the mechanisms involved in the major cachexia target tissues, we investigated the entire transcriptome in muscle and fat to identify altered …

Novel Techniques For Investigating The Regulation Of Skeletal Muscle Hemodynamics, Baraa K. Al-Khazraji

Electronic Thesis and Dissertation Repository

The effect of the sympathetic nervous system (SNS) on blood flow distribution within skeletal muscle microvasculature is conditional upon regional activation of SNS receptors. Due to a lack of appropriate experimental models and techniques, no study has systematically evaluated the effect of SNS receptor activation in continuously branching skeletal muscle arteriolar trees. In line with previous work, we hypothesize that there will be a spatially-dependent distribution of sympathetic receptor activation along the arteriolar tree. Specifically, we anticipate a progressive decrease of adrenergic activation and a progressive increase of peptidergic and purinergic activation with increasing arteriolar order. We developed a novel …

Tumor-Derived Proteins And Mitochondrial Dysfunction In Lung Cancer-Induced Cachexia, Julie B. Mclean

Theses and Dissertations--Physiology

Lung tumors secrete multiple factors that contribute to cachexia, a severe wasting syndrome that includes loss of muscle mass, weakness, and fatigue. 80% of advanced lung cancer patients experience cachexia, which cannot be reversed by nutritional interventions, diminishes response to and tolerance of cancer treatments, and increases morbidity and mortality. Despite a multitude of clinical trials, there are currently no approved treatments. This deficiency suggests that not all of the factors that contribute to cachexia have been identified.

Cancer is frequently accompanied by an increase in cyclooxygenase-2 (COX-2), a hallmark of inflammation. Clinical trials for COX-2 inhibitors have resulted in …

Impaired Glucose Metabolism In The Absence Of Skeletal Muscle Brain And Muscle Arnt-Like-Protein 1 (Bmal1), Brianna D. Harfmann

Theses and Dissertations--Physiology

Metabolism is a critical physiological function that works to generate energy for cells, store substrates and maintain homoeostasis. Alterations in normal metabolism can have a severe effect on physiology, leading to metabolic disease. Skeletal muscle is a key metabolic tissue, taking up ~80% of postprandial glucose. Therefore it contributes considerably to glucose metabolism: glucose uptake, oxidation and homeostasis. To address the role of the skeletal muscle clock in insulin sensitivity and glucose tolerance, our lab generated an inducible skeletal muscle specific Bmal1^-/- mouse (iMSBmal1^-/-). 5 weeks post-recombination we observed impairment in both insulin- and AICAR-stimulated skeletal …

Global-Scale Analysis Of The Dynamic Transcriptional Adaptations Within Skeletal Muscle During Hypertrophic Growth, Tyler Kirby

Theses and Dissertations--Physiology

Skeletal muscle possesses remarkable plasticity in responses to altered mechanical load. An established murine model used to increase mechanical load on a muscle is the surgical removal of the gastrocnemius and soleus muscles, thereby placing a functional overload on the plantaris muscle. As a consequence, there is hypertrophic growth of the plantaris muscle. We used this model to study the molecular mechanisms regulating skeletal muscle hypertrophy.

Aged skeletal muscle demonstrates blunted hypertrophic growth in response to functional overload. We hypothesized that an alteration in gene expression would contribute to the blunted hypertrophic response observed with aging. However, the difference in …

Gdnf Content And Nmj Plasticity In Slow And Fast Twitch Myofibers Follows Recruitment In Exercise, Amy Morrison Gyorkos

Dissertations

Glial cell-line derived neurotrophic factor (GDNF) supports and maintains the neuromuscular system during development and through adulthood by promoting neuroplasticity. GDNF may play a role in delaying the onset of aging and help compress morbidity by preventing motor unit degeneration. Exercise has been shown to alter GDNF expression differently in slow and fast twitch myofibers. The aim of this dissertation project is to determine if different intensities of exercise can promote changes in GDNF expression and neuromuscular junction (NMJ) morphology in slow and fast twitch muscle fibers. Skeletal muscle fibers were analyzed from adult Sprague Dawley rats aged 4 weeks …

The Roles Of Mammalian Tribbles Homolog 3 (Trib3) In Coordinating Energy Metabolism And Development Of Insulin Resistance, Wei Zhang

All ETDs from UAB

Insulin resistance in diabetics comprises of a reversible component treatable with intensive glycemic control and a non-reversible component present in pre-diabetes that may lead to the development of overt diabetes. The reversible component is induced and exacerbated by hyperglycemia in both uncontrolled type 1 and type 2 diabetes, a process known as glucose-induced insulin resistance (GIIR) or glucose toxicity. The tribbles homolog 3 (TRIB3) has been identified as a pseudokinase that inhibits Akt activity by physically blocking its phosphorylation site. Expression of TRIB3 has been associated with various signals such as endoplasmic reticulum (ER) stress and nutrient availability in pancreatic …

The Effect Of Liver X Receptor Α Deficiency In Skeletal Muscle On Lipid Content In Mice, Yishu Ding

All ETDs from UAB

Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. Many researchs focus on the liver, but tissue-specific roles of LXRs in other tissues remain elusive. Based on in vitro studies on cultured cells, the roles of LXRs in skeletal muscle have been proposed. Nevertheless, the in vivo roles of LXRs in skeletal muscle remain lacking. Skeletal muscle is an important insulin targeting tissue, which plays a key role in regulating insulin sensitivity. Abnormal lipid metabolism and homeostasis have been demonstrated to play a crucial role in the development of insulin resistance in skeletal muscle. To …

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz

All ETDs from UAB

THE ROLE OF TRIB3 IN INSULIN RESISTANCE: ITS ACTION AS NUTRIENT SENSOR AND REGULATOR OF INSULIN ACTION JIARONG LIU LAMIQUIZ PATHOLOGY ABSTRACT Insulin resistance is a hallmark of Type 2 diabetes (T2DM). A reduced capacity for insulin to stimulate increases in glucose uptake and glucose oxidation in insulin sensitive tissues, such as skeletal muscle and adipose tissue, are common defects in patients with insulin resistance, T2DM, and other related diseases. Tribbles homolog 3 (TRIB3) has been demonstrated to play a role in insulin resistance by serving as a negative regulator of Akt in mouse liver, fat, and pancreas. In a …

Lean And Obese Zucker Rats Exhibit Different Patterns Of P70s6kinase Regulation In The Tibialis Anterior Muscle In Response To High Force Muscle Contraction, Anjaiah Katta

Theses, Dissertations and Capstones

Increased muscle loading results in phosphorylation of the 70 kDa ribosomal S6 kinase (p70s6k) signaling pathway and this event strongly correlates with degree of muscle adaptation following resistance exercise. Here, we compared the basal and contraction- induced phosphorylation of p70s6k, Akt and mTOR in tibialis anterior muscles of lean and obese Zucker rats. Immunoblotting demonstrated differences in level of basal p70S6k phosphorylation (Thr 389) in the normal and diabetic TA. HFES had an increase in p70S6k (Thr389) phosphorylation at 0-, 1- and 3-hr in lean TA and only at 3-hr in obese TA. mTOR (Ser 2448) Phosphorylation was elevated in …