Sarcopenia and systemic inflammation are associated with decreased survival after cytoreductive nephrectomy for metastatic renal cell carcinoma
Background: This study was aimed at assessing the associations of sarcopenia, muscle density, adiposity, and inflammation with overall survival (OS) after cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma.
Methods: In all, 158 patients undergoing CN from 2001 to 2014 had digitized preoperative imaging for tissue segmentation via Slice-O-Matic software (version 5.0) at the mid-L3 level. The skeletal muscle index was calculated with the skeletal muscle area (cm2 ) normalized for height (m2 ), and the skeletal muscle density (SMD) was calculated with average Hounsfield units. Adiposity was measured with the cross-sectional area (cm2 ) of visceral, subcutaneous, and intramuscular adiposity compartments and was similarly normalized for height. The average fat density was obtained in Hounsfield units. OS was estimated with the Kaplan-Meier method. Associations between body composition, inflammation metrics, and relevant clinicopathology and OS were assessed with univariable and multivariate Cox analyses.
Results: Seventy-six of the 158 patients (48%) were sarcopenic. Sarcopenia was associated with elevated neutrophil to lymphocyte ratios (NLRs; P = .02), increased age (P = .001), lower body mass indices (P = .009), greater modified Motzer scores (P = .019), and lower SMD (P = .006). The median OS was 15.0 and 29.4 months for sarcopenic and nonsarcopenic patients, respectively (P = .04). Elevated inflammation (NLR or C-reactive protein), in addition to sarcopenia, was independently associated with OS, with an elevated NLR ≥ 3.5 and sarcopenia associated with the poorest OS at 10.2 months. No associations were observed between measurements of muscle density or adiposity and OS.
Conclusions: Sarcopenia and measures of high systemic inflammation are additively associated with inferior OS after CN and may be of use in preoperative risk stratification.
Lay summary: Body composition and sarcopenia (a deficiency in skeletal musculature) have been shown to affect outcomes in cancer. We found that sarcopenic patients had poor survival in comparison with nonsarcopenic patients in the setting of metastatic renal cell carcinoma (mRCC). Patients with both elevated inflammation and sarcopenia had the poorest survival. Sarcopenia is an objective measure of nutrition that can assist in therapeutic counseling and decision-making for individualized treatment in mRCC.
Amir Ishaq Khan
Sarah P Psutka
Dattatraya H Patil
Gordon Hong
Milton A Williams
Mehmet A Bilen
Aarti Sekhar
Haydn T Kissick
Vikram M Narayan
Shreyas S Joshi
Kenneth Ogan
Viraj A Master
Cancer
. 2022 Jun 1;128(11):2073-2084. doi: 10.1002/cncr.34174. Epub 2022 Mar 14.
2022
English
Recommended musculoskeletal and sports ultrasound terminology: a Delphi-based consensus statement
The current lack of agreement regarding standardised terminology in musculoskeletal and sports ultrasound presents challenges in education, clinical practice and research. This consensus was developed to provide a reference to improve clarity and consistency in communication. A multidisciplinary expert panel was convened consisting of 18 members representing multiple specialty societies identified as key stakeholders in musculoskeletal and sports ultrasound. A Delphi process was used to reach consensus, which was defined as group level agreement of >80%. Content was organised into seven general topics including: (1) general definitions, (2) equipment and transducer manipulation, (3) anatomical and descriptive terminology, (4) pathology, (5) procedural terminology, (6) image labelling and (7) documentation. Terms and definitions which reached consensus agreement are presented herein. The historic use of multiple similar terms in the absence of precise definitions has led to confusion when conveying information between colleagues, patients and third-party payers. This multidisciplinary expert consensus addresses multiple areas of variability in diagnostic ultrasound imaging and ultrasound-guided procedures related to musculoskeletal and sports medicine.
Mederic M Hall
Georgina M Allen
Sandra Allison
Joseph Craig
Joseph P DeAngelis
Patricia B Delzell
Jonathan T Finnoff
Rachel M Frank
Atul Gupta
Douglas Hoffman
Jon A Jacobson
Samer Narouze
Levon Nazarian
Kentaro Onishi
Jeremiah Wayne Ray
Luca Maria Sconfienza
Jay Smith
Alberto Tagliafico
Br J Sports Med
. 2022 Mar;56(6):310-319. doi: 10.1136/bjsports-2021-105114. Epub 2022 Feb 2.
2022
English
Neural Organization Of Spindles In 3 Hindlimb Muscles Of The Rat
Anatomy & Morphology; cat tenuissimus muscle; expression; fusimotor innervation; intrafusal fibers; lumbrical muscles; motor innervation; muscle; nuclear chain fibers; skeletofusimotor; soleus; ultrastructure
Kucera J; Walro J M; Reichler J
American Journal of Anatomy
1991
1991-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/aja.1001900107" target="_blank" rel="noreferrer noopener">10.1002/aja.1001900107</a>
Transient Expression Of A Slow-tonic Mhc Isoform By Extrafusal Fibers In The Developing Rat
Anatomy & Morphology; denervation; Developmental Biology; diversity; extrafusal fibers; intrafusal fibers; intrafusal muscle-fibers; monoclonal-antibody; motor innervation; muscle; myosin heavy-chain; neonatal rats; skeletal-muscle; slow-tonic myosin; spindles
ALD 19, a monoclonal antibody that recognizes the slow-tonic myosin heavy chain (MHC) isoform, has been used extensively as a marker for nuclear bag intrafusal fibers of muscle spindles in developing and adult rats. Extrafusal fibers of adult rat hindlimb muscles do not express slow-tonic MHC. However, while using ALD 19 to trace the fate of intrafusal fibers following neonatal denervation, we noted that some extrafusal fibers of neonates also bound this antibody. The immunolabeled extrafusal fibers were a subset of slow fibers located in the deep axial regions of crural muscles. The same fiber subset transiently displayed a weak affinity for ALD 19 during the first postnatal week in normal muscles. Denervation at birth increased the intensity of ALD 19 immunolabelling by these extrafusal fibers and extended the duration of the slow-tonic immunoreactivity into the 2nd postnatal week, after which expression diminished or ceased. Demonstration that some developing extrafusal fibers have a nerve-independent capacity for transiently expressing slow-tonic MHC, an MHC previously thought to be expressed only by intrafusal fibers, raises the possibility that both types of fiber originate from a subset of bipotential slow primary myotubes in rat hindlimbs.
Kucera J; Walro J M
Anatomy and Embryology
1993
1993-10
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1007/bf00185950" target="_blank" rel="noreferrer noopener">10.1007/bf00185950</a>
Sequences Of Intrafusal Fiber Formation Are Muscle-dependent In Rat Hindlimbs
Anatomy & Morphology; cat; development; Developmental Biology; embryonic-development; expression; innervation; intrafusal fibers; motor; muscle; muscle spindles; myosin heavy chains; myosin heavy-chain; neonatal rats; skeletal-muscle; slow myosin; spindles; tenuissimus muscles
A rat muscle spindle typically contains four intrafusal fibers - one nuclear bag(2), one nuclear bag, and two nuclear chain fibers. We compared the sequence of formation of the three intrafusal fiber types among the tibialis anterior (TA), soleus (SOL) and medial gastrocnemius (RIG) muscles using immunocytochemistry of spindle-specific myosin heavy chain isoforms. Spindles of the TA began to differentiate earlier and acquired the full complement of intrafusal fibers sooner than spindles of the SOL or MG muscles. At the onset of spindle assembly, the intrafusal myotubes expressed myosin heavy chains similar to those expressed by extrafusal myotubes. The first intrafusal myotube then differentiated into the bag, fiber regardless of the muscle. However, the fate of the second-forming intrafusal myotube varied among the muscles studied. It usually differentiated into a chain fiber in the TA, into a bag(1) fiber in the SOL, and into either a bag(1) or a chain in the MG. The fate of the third-forminge was reciprocal to that of the second; i.e. in those spindles in which the bag(1) fiber was second to form, a chain was third, and vice versa. The fourth and last intrafusal myotube gave rise to a chain fiber. The inter- and intramuscular variability in the fate of intrafusal myotubes of the second and third generation argues against the existence of a program intrinsic to the myotubes that would mandate their differentiation along specific paths. Rather, an extrinsic regulatory factor, probably associated with the primary afferent neuron, may govern differentiation of pluripotential myotubes into particular types of intrafusal fiber. The fate of the intrafusal myotubes might then depend on the timing of the regulatory effect of afferents relative to the stage of development of the intrafusal bundle.
Kucera J; Walro J M
Anatomy and Embryology
1994
1994-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1007/bf00234305" target="_blank" rel="noreferrer noopener">10.1007/bf00234305</a>
Origin Of Intrafusal Fibers From A Subset Of Primary Myotubes In The Rat
afferents; Anatomy & Morphology; development; Developmental Biology; developmental myosins; expression; intrafusal fibers; isoforms; muscle; muscle spindles; muscle spindles; myosin heavy chains; myosin heavy-chain
S46, a monoclonal antibody (mAb) specific for the SM-1 and SM-2 isoforms of avian slow myosin heavy chains (MHC), was used to study the earliest stages of development of intrafusal fibers in muscle spindles of the rat hindlimb. Spindles formed only in the regions of fetal muscles that contained primary myotubes reactive to mAb S46, such as the axial region of the tibialis anterior muscle. The first intrafusal fiber to form, the nuclear bag, fiber, originated from within the population of S46-reactive primary myotubes. Binding of mAb S46 by myotubes giving rise to the bag, fibers preceded the appearance of encapsulated spindles in the muscles by electron microscopy. However, reactivity to S46 intensified in the myotubes transforming into bag, fibers after the innervation of the fibers by afferents, and dissipated in myotubes differentiating into slow-twitch (type I) extrafusal fibers. Thus, afferents may enhance intrafusal expression of the MHC isoform reactive to mAb S46. The pattern of S46 binding to nuclear bag and chain intrafusal fibers in both developing and adult spindles was the same as that reported for the mAb ALD19, suggesting that both antibodies bind to the same MHC isoform. This isoform is probably a developmental form of slow myosin, because it was transiently expressed during the development of type I extrafusal fibers. The origin of bag, intrafusal and type I extrafusal fibers from a bipotential subpopulation of primary myotubes reactive to mAb S46 correlates with the location of muscle spindles in the slow regions of muscles in adult rat hindlimbs.
Kucera J; Walro J M
Anatomy and Embryology
1995
1995-08
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1007/bf00186003" target="_blank" rel="noreferrer noopener">10.1007/bf00186003</a>
Formation Of Muscle-spindles In The Absence Of Motor Innervation
afferent; differentiation; efferent; fibers; intrafusal muscle fiber; muscle; nerve; Neurosciences & Neurology; rat; spindle development
Whether muscle spindles can form in muscles innervated only by afferents was investigated by removing the lumbosacral segment of the spinal cord immediately after crushing the nerve to the medial gastrocnemius (MG) muscle in newborn rats, and administering nerve growth factor for 10 days afterwards. The nerve-crushed MG muscles reinnervated by afferents in the absence of motor innervation were examined at postnatal (P) days 7, 9 and 30 for the presence of spindles by light and electron miscroscope. Reinnervated MG muscles contained spindle-like encapsulations of 1-4 fibers at 7, 9 and 30 days after the nerve crush. The number of spindles exceeded that of normal MG muscles, suggestive of de novo formation of spindles. All nerve-muscle contacts in the spindles had features of sensory endings, and intrafusal fibers expressed the spindle-specific slow-tonic myosin heavy chain (MHC) isoform at P30. No motor endplates were visible on any muscle fibers and extrafusal fibers were atrophied, as would be predicted in the absence of motor innervation. Thus, efferents are not essential for the formation and differentiation of muscle spindles in reinnervated muscles of neonatal rats.
Kucera J; Walro J M
Neuroscience Letters
1992
1992-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0304-3940(92)90200-q" target="_blank" rel="noreferrer noopener">10.1016/0304-3940(92)90200-q</a>
Functional And Evolutionary Significance Of The Recruitment And Firing Patterns Of The Jaw Adductors During Chewing In Verreaux's Sifaka (propithecus Verreauxi)
Anthropology; biomechanics; bone-strain; electromyography; Evolutionary Biology; Force; fusion; lemurs lemur-catta; macaca-fascicularis; mandibular symphysis; masseter force; mastication; muscle; primates; strepsirrhines; wishboning
Jaw-muscle electromyographic (EMG) patterns indicate that compared with thick-tailed galagos and ring-tailed lemurs, anthropoids recruit more relative EMG from their balancing-side deep masseter, and that this muscle peaks late in the power stroke. These recruitment and firing patterns in anthropoids are thought to cause the mandibular symphysis to wishbone (lateral transverse bending), resulting in relatively high symphyseal stresses. We test the hypothesis that living strepsirrhines with robust, partially fused symphyses have muscle recruitment and firing patterns more similar to anthropoids, unlike those strepsirrhines with highly mobile unfused symphyses. Electromyographic (EMG) activity of the superficial and deep masseter, anterior and posterior temporalis, and medial pterygoid muscles were recorded in four dentally adult Verreaux's sifakas (Propithecus verreauxi). As predicted, we find that sifaka motor patterns are more similar to anthropoids. For example, among sifakas, recruitment levels of the balancing-side (b-s) deep masseter are high, and the b-s deep masseter fires late during the power stroke. As adult sifakas often exhibit nearly complete symphyseal fusion, these data support the hypothesis that the evolution of symphyseal fusion in primates is functionally linked to wishboning. Furthermore, these data provide compelling evidence for the convergent evolution of the wishboning motor patterns in anthropoids and sifakas. Am J Phys Anthropol 145:531-547, 2011. (C) 2011 Wiley-Liss, Inc.
Hylander W L; Vinyard C J; Wall C E; Williams S H; Johnsonl K R
American Journal of Physical Anthropology
2011
2011-08
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/ajpa.21529" target="_blank" rel="noreferrer noopener">10.1002/ajpa.21529</a>
Dopexamine Hydrochloride In Septic Shock
consumption; dobutamine; dopexamine hydrochloride; endotoxic dogs; General & Internal Medicine; heart failure; infusion; inotropic support; lactate; muscle; O-2 transport; O-2 uptake; optimal values; oxygen delivery; Respiratory System; respiratory-distress syndrome; sepsis; septic shock; tissue oxygenation; volume support
Objective: To test whether dopexamine hydrochloride, by its beta(2)-adrenoceptor and dopaminergic 1 (DA(1)) and dopaminergic 2 (DA(2)) agonistic properties, can improve oxygen consumption (V over dot O-2) in hyperdynamic patients with septic shock. Design: Prospective, single-cohort study. Setting: ICU, university hospital. Patients: Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Interventions: Short-term application (30 min) of dopexamine hydrochloride at a dose of 2 mu g/kg/min. Measurements: Complete hemodynamic profile with O-2 transport-related variables at baseline, 30 min after starting the dopexamine infusion, and 30 min after stopping the infusion. Main results: The dopexamine infusion resulted in significant increases in cardiac index (17%) (p<0.001) and O-2 delivery (DO2) (16%) (p<0.001), V over dot O-2 increased slightly but significantly about 4% (p<0.01) by respiratory gas exchange measurements and 9% (p<0.01) by cardiovascular Fick calculations. The O-2 extraction ratio decreased about 8% (0.001). Conclusions: The addition of dopexamine hydrochloride at a dose of 2 mu g/kg/min resulted in significant increases of DO2 and to a lesser extent V over dot O-2. Much of the global DO2 increase was not utilized, because O-2 extraction ratio decreased. Direct calorigenic effects of dopexamine and an increase in myocardial V over dot O-2 likely account for a large portion of the increase in global V over dot O-2. Whether any of the V over dot O-2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this lug in septic shock can be established.
Hannemann L; Reinhart K; Meierhellmann A; Wallenfang G; Bredle D L
Chest
1996
1996-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1378/chest.109.3.756" target="_blank" rel="noreferrer noopener">10.1378/chest.109.3.756</a>
Variation In The Timing And Frequency Of Sucking And Swallowing Over An Entire Feeding Session In The Infant Pig Sus Scrofa
activity; anesthesia; Animal model; Deglutition; disorders; dysphagia; Feeding; food transport; Infant; intraoral transport; laryngeal nerve lesion; model; muscle; Otorhinolaryngology; Pediatric; reflex pharyngeal swallow; rhythmic oral; validation
Gierbolini-Norat E M; Holman S D; Ding P; Bakshi S; German R Z
Dysphagia
2014
2014-08
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1007/s00455-014-9532-y" target="_blank" rel="noreferrer noopener">10.1007/s00455-014-9532-y</a>
Growth And Repair Factors, Osteoactivin, Matrix Metalloproteinase And Heat Shock Protein 72, Increase With Resolution Of Inflammation In Musculotendinous Tissues In A Rat Model Of Repetitive Grasping
carpal-tunnel-syndrome; disorders; endothelial-cells; extracellular-matrix; gene-expression; Heat shock protein; human fibroblasts; Metalloproteinases; muscle; musculoskeletal; Orthopedics; Osteoactivin; Overuse; posttranscriptional; regulation; Restorative repair; Rheumatology; skeletal-muscle regeneration; Tendon; transgenic expression; upper extremity
Frara N; Abdelmagid S M; Tytell M; Amin M; Popoff S N; Safadi F F; Barbe M F
Bmc Musculoskeletal Disorders
2016
2016-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1186/s12891-016-0892-3" target="_blank" rel="noreferrer noopener">10.1186/s12891-016-0892-3</a>
Effects Of Topical Brinzolamide On Infantile Nystagmus Syndrome Waveforms: Eyedrops For Nystagmus
amaurosis; carbonic-anhydrase activity; congenital nystagmus; gene transfer; innervation; muscle; Neurosciences & Neurology; ocular motor system; Ophthalmology; rat; Surgery; tenotomy
Dell'Osso L F; Hertle R W; Leigh R J; Jacobs J B; King S; Yaniglos S
Journal of Neuro-Ophthalmology
2011
2011-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1097/WNO.0b013e3182236427" target="_blank" rel="noreferrer noopener">10.1097/WNO.0b013e3182236427</a>
Overview of FEED, the Feeding Experiments End-user Database
Biology; coordination; evolution; fishes; infant; jaw; motor control; muscle; patterns; vertebrates; Zoology
The Feeding Experiments End-user Database (FEED) is a research tool developed by the Mammalian Feeding Working Group at the National Evolutionary Synthesis Center that permits synthetic, evolutionary analyses of the physiology of mammalian feeding. The tasks of the Working Group are to compile physiologic data sets into a uniform digital format stored at a central source, develop a standardized terminology for describing and organizing the data, and carry out a set of novel analyses using FEED. FEED contains raw physiologic data linked to extensive metadata. It serves as an archive for a large number of existing data sets and a repository for future data sets. The metadata are stored as text and images that describe experimental protocols, research subjects, and anatomical information. The metadata incorporate controlled vocabularies to allow consistent use of the terms used to describe and organize the physiologic data. The planned analyses address long-standing questions concerning the phylogenetic distribution of phenotypes involving muscle anatomy and feeding physiology among mammals, the presence and nature of motor pattern conservation in the mammalian feeding muscles, and the extent to which suckling constrains the evolution of feeding behavior in adult mammals. We expect FEED to be a growing digital archive that will facilitate new research into understanding the evolution of feeding anatomy.
Wall C E; Vinyard C J; Williams S H; Gapeyev V; Liu X H; Lapp H; German R Z
Integrative and Comparative Biology
2011
2011-08
Journal Article
<a href="http://doi.org/10.1093/icb/icr047" target="_blank" rel="noreferrer noopener">10.1093/icb/icr047</a>
Using electromyography as a research tool in food science
chewing behavior; emg; Food Science & Technology; force; mastication; muscle; normalization; patterns; release; surface electromyography; texture-perception
The jaw muscles play key functional roles during feeding. During contraction, a bioelectrical signal propagates along the muscle cell helping to coordinate muscle contraction. This signal can be measured via electromyography (EMG). Food scientists have increasingly adopted EMG as a tool for studying the relationships among food textures and oral processing. Specifically, food scientists have used EMG from the feeding muscles as (1) a general measure of food texture, (2) a measure of oral physiology, (3) an estimate of absolute force and (4) a measure of muscle work. Unfortunately, physiological research indicates that estimates of absolute force and mechanical work are not reliably indicated from EMG as it is best considered an indicator of muscle activity and relative recruitment levels.
Vinyard C J; Fiszman S
Current Opinion in Food Science
2016
2016-06
Journal Article
<a href="http://doi.org/10.1016/j.cofs.2016.06.003" target="_blank" rel="noreferrer noopener">10.1016/j.cofs.2016.06.003</a>
Preference and consequences: A preliminary look at whether preference impacts oral processing in non-human primates
Anthropology; bitter taste; cebus-apella; chewing behavior; electromyography; Evolutionary Biology; fallback foods; Feeding; Food mechanical properties; Food preference; hardness; mastication; mechanical properties; model foods; muscle; patterns; texture
Non-human primates demonstrate food preferences much like humans. We have little insight, however, into how those preferences impact oral processing in primates. To begin describing this relationship, we conducted a preliminary analysis measuring food preference in two tufted capuchins (Cebus apella) and comparing ranked preference to physiological variables during chewing of these foods. Food preference was assessed for each monkey across 12 foods, including monkey biscuits and 11 foods consumed by humans (e.g., various fruits and nuts). Animals chose from randomized pairs of foods to generate a ranked scale across the 12 foods. Contemporaneous with preference testing, electromyographic (EMG) activity was measured for the jaw-closing muscles to assess oral physiology during chewing of these foods. As expected, these capuchins exhibited clear preferences among these 12 foods. Based on their preferences, we identified sets of preferred and non-preferred brittle (i.e., almond versus monkey chow) and ductile (i.e., dates and prunes versus apricots) foods for physiological comparisons that broadly control variation in food mechanical properties (FMPs). As expected, oral physiology varied with FMPs in each animal. Within brittle and ductile groupings, we observed several significant differences in chewing cycle length and relative muscle activation levels that are likely related to food preference. These differences tended to be complex and individual specific. The two capuchins chewed non-preferred apricots significantly faster than preferred dates and prunes. Effect sizes for preference were smaller than those for FMPs, supporting the previous focus on FMPs in primate dietary research. Although preliminary, these results suggest that food preference may influence oral physiology in non-human primates. The prospect that this relationship exists in monkeys raises the possibility that a link between food preference and oral processing in humans may be based on shared tendencies with non-human primates, such as aversion to bitter items or preference for sweet foods. (C) 2016 Elsevier Ltd. All rights reserved.
Vinyard C J; Thompson C L; Doherty A; Robl N
Journal of Human Evolution
2016
2016-09
Journal Article
<a href="http://doi.org/10.1016/j.jhevol.2016.07.001" target="_blank" rel="noreferrer noopener">10.1016/j.jhevol.2016.07.001</a>
Androgen-receptor defect abolishes sex differences in nitric oxide and reactivity to vasopressin in rat aorta
aorta; arginine vasopressin; binding; brain; dependent gender differences; dimorphism; Endothelium; endothelium-derived relaxing factor; estrogen; gonadal steroid hormones; hormones; l-arginine; muscle; Physiology; Sport Sciences; testicular feminized rat; testicular feminized rat; vasoconstriction
Contractions of rat thoracic aorta to vasopressin WP) are threefold higher in females (F) than in males (M), primarily because nitric oxide (NO) attenuation of contraction is greater in M. To determine the role of the androgen receptor (AR) in this mechanism, vascular reactivity to VP was examined in thoracic aorta of the testicular-feminized male (Tfm) rat, which has an X-linked, recessive defect in AR function in affected M. Maximal contraction of normal aortas to VP was fourfold higher in F (4,128 +/- 291 mg/mg ring wt) than in M (971 +/- 133 mg); maximal response of Tfm (3,967 +/- 253 mg) was similar to that of normal F. N-G-nitro-L-arginine methyl ester increased maximal response to VP threefold in M but had no effect in F or Tfm. In contrast, maximal contraction of normal aortas to phenylephrine was 43% higher in M (4,011 +/- 179 mg) than in F (2,809 +/- 78 mg); maximal response of Tfm (2,716 +/- 126 mg) was similar to that of normal F. N-G-nitro-L-arginine methyl ester increased maximal response to phenylephrine by >50% in F and Tfm but had no effect in M. Maximal contractile response to 80 mM KCl did not differ among M, F, or Tfm. Thus androgens and normal vascular AR function are important in the greater NO-mediated attenuation of reactivity to VP in M than in F rat aorta, which may involve specific modulation of endothelial VP signal transduction pathways and NO release by androgens. These data also establish the importance of the Tfm rat as a model to study the effects of androgens on cardiovascular function.
Stallone J N; Salisbury R L; Fulton C T
Journal of Applied Physiology
2001
2001-12
Journal Article
<a href="http://doi.org/10.1152/jappl.2001.91.6.2602" target="_blank" rel="noreferrer noopener">10.1152/jappl.2001.91.6.2602</a>
Evidence from surface microscopy for recognition of fleshy and tendinous muscle insertion in extant vertebrate femora: implications for muscle reconstruction in fossils
attachment sites; bird; birds neornithes; bone-tendon; Dinosaur; entheseal changes; evolution; Life Sciences & Biomedicine - Other Topics; mammal; mechanical load; muscle; musculoskeletal stress markers; Paleontology; pelvic musculature; reptile; soft-tissues; tendon; upper-limb
Recognition of muscle attachment sites and their modification has been an important tool in anthropologic and paleontologic research, but has been compromised by limited ability to recognise sites of tendinous attachments. We investigated bone-tendon (three sites) and bone-muscle (six sites) interfaces in six pairs of femora across a broad taxonomic spectrum of higher amniote archosaurs (both recent and fossil) by epi-illumination microscopy. Direct fleshy and indirect tendinous muscle attachments were identified by dissection of fresh specimens and examination of fossils and the surface microscopic changes identified at those locations. Examination revealed bone modifications specific to each type of muscle insertion, allowing them to be identified and distinguished. Application of a surface microscopy technique not only permits more confident localisation of tendinous attachments, but for the first time allows recognition of sites of direct fleshy muscle attachments - in a reproducible manner across phylogenetic lines.
Rothschild B M; Wilhite D R; McLeod D S; Ting H
Historical Biology
2016
2016-08
Journal Article
<a href="http://doi.org/10.1080/08912963.2015.1049163" target="_blank" rel="noreferrer noopener">10.1080/08912963.2015.1049163</a>
The use of sensory electrical stimulation for pressure ulcer prevention.
Adult; Humans; Male; Middle Aged; Ohio; Aged; Double-Blind Method; Regional Blood Flow; *Electric Stimulation Therapy; Buttocks; Muscle Contraction; Paralysis/etiology/physiopathology/*therapy; Pressure Ulcer/etiology/physiopathology/*prevention & control; Sensory Thresholds; Spinal Cord Injuries/complications/physiopathology/*therapy; Treatment Failure; Tomography; Human; Funding Source; Repeated Measures; Outcome Assessment; Clinical Trials; Middle Age; X-Ray Computed; Muscle; Blood Gas Monitoring; Skeletal/blood supply/diagnostic imaging/*innervation; Transcutaneous; Double-Blind Studies; Interface Pressure; Spinal Cord Injuries; Time Series; Pressure Ulcer – Prevention and Control; Electric Stimulation – Methods; Electric Stimulation – Utilization; Skeletal – Radiography
Pressure ulcer prevention is critically important for many people with reduced mobility. The authors investigated whether sensory (sub-motor-threshold) electrical stimulation (ES) may provide a convenient preventive intervention. A double-blinded, repeated measures study design was used to test the hypothesis that repeated use of sensory surface ES improves tissue health status in individuals with motor paralysis. Six adult males with complete spinal cord injury (SCI) were randomly assigned to treatment or control groups. The treatment group received the ES intervention, whereas the control group received a control sham intervention. Repeated tissue health assessments included transcutaneous oxygen tension (T(c)PO(2)), interface pressure mapping, and gluteal computed tomography (CT) studies. An initial increase in T(c)PO(2) following use of subthreshold ES was observed but was not sustained at follow-up. No statistically significant changes before and after treatment were found in regional T(c)PO(2), gluteal muscle area or pressure distribution. Thus subthreshold ES does not appear to have any sustained effects on tissue health status indicative of reduced pressure ulcer risk for individuals with SCI. This implies that a contractile muscle response is critically important and further that subthreshold ES is unlikely to prevent pressure ulcers. Further studies are needed to find solutions for preventing pressure ulcers in high-risk populations.
Kim Jennifer; Ho Chester H; Wang Xiaofeng; Bogie Kath
Physiotherapy theory and practice
2010
2010-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3109/09593981003587037" target="_blank" rel="noreferrer noopener">10.3109/09593981003587037</a>
Acute exercise attenuates phenylephrine-induced contraction of rabbit isolated aortic rings.
Animals; Rabbits; In Vitro Techniques; Phenylephrine/*pharmacology; Aorta/physiology; Muscle Contraction/*drug effects; Dose-Response Relationship; Drug; Muscle; Receptors; Animal; Smooth; Adrenergic; *Physical Conditioning; alpha/physiology; Vascular/*drug effects/physiology
Factors associated with a single bout of dynamic exercise (increased circulating catecholamines, increased body temperature, and decreased pH) are known to attenuate the vascular response to alpha-adrenergic receptor activation. Therefore, we postulate that an acute bout of dynamic exercise may decrease the vascular response to catecholamines. To test this hypothesis, we evaluated contractile responsiveness to phenylephrine (PE) in aortae of two groups of New Zealand white rabbits, a control group (no exercise) and an exercise group (treadmill running, 24m.min-1; 16 +/- 2.0 min). Aortic rings were prepared from age-matched control (N = 6) and exercise rabbits (N = 5) and mounted for isometric tension recording (in Krebs-Henseleit-bicarbonate solution, 37 degrees C, 1.5 g passive tension). After equilibration (2 h) a cumulative concentration-response curve to PE (10(-7) M-10(-2) M) was obtained. The results demonstrate that a single bout of dynamic exercise attenuates (P \textless 0.05) the maximal contractile tension (2,457 +/- 120 vs 3,620 +/- 321 mg tension.mg-1 ring wt), gain (602 +/- 31 vs 878 +/- 87 mg.M-1 PE), and rate of contraction (6.2 +/- 0.3 vs 4.7 +/- 0.3 mg tension.s-1). In addition, contraction threshold was significantly increased in exercise (2.6 +/- 0.4 x 10(-6) M) vs control aortae (1.03 +/- 0.4 x 10(-6) M). A single bout of dynamic exercise did not alter the contractile response to 70 mM KCl (3,555 +/- 270 vs 3,083 +/- 233 mg tension.mg-1 ring weight). These data suggest that an acute bout of dynamic exercise significantly attenuates alpha-adrenergic receptor-mediated contraction of vascular smooth muscle.
Howard M G; DiCarlo S E; Stallone J N
Medicine and science in sports and exercise
1992
1992-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1249/00005768-199210000-00006" target="_blank" rel="noreferrer noopener">10.1249/00005768-199210000-00006</a>
Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice.
Adipose Tissue; Adiposity/genetics; Animals; Brown/pathology; Carcinoma/etiology/*genetics; Cell Transformation; Cytoplasmic and Nuclear/*deficiency/genetics; Diet; Dietary Fats/metabolism; Energy Metabolism/genetics; Female; Gene Knockout Techniques; Glucose Intolerance/complications/genetics; High-Fat/*adverse effects; Intestinal Absorption; Knockout; Leptin/deficiency/genetics; Liver Neoplasms/etiology/*genetics; Liver/pathology; Male; Mice; Muscle; Neoplastic/genetics; Obese; Obesity/*etiology/genetics; Receptors; Sex Factors; Skeletal/metabolism; Weight Gain/genetics
Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (\textgreater12 months old) Fxr(-/-) mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr(-/-)) mice, the Ldlr(-/-)Fxr(-/-) double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr(-/-) background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr(-/-) mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr(-/-) mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob(-/-)Fxr(-/-) mice that were deficient in both Leptin and Fxr. On a chow diet, ob(-/-)Fxr(-/-) mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (\textless11 months old) Ob(-/-)Fxr(-/-) mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.
Zhang Yanqiao; Ge Xuemei; Heemstra Lydia A; Chen Wei-Dong; Xu Jiesi; Smith Joseph L; Ma Huiyan; Kasim Neda; Edwards Peter A; Novak Colleen M
Molecular endocrinology (Baltimore, Md.)
2012
2012-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1210/me.2011-1157" target="_blank" rel="noreferrer noopener">10.1210/me.2011-1157</a>
Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling.
Adenosine Triphosphate – Metabolism; Adenosine Triphosphate/*metabolism; Animal Studies; Animals; contrast echocardiography; Equipment and Supplies; Hemodynamics; Humans; Inbred C57BL; Male; Mice; microbubbles; Microbubbles; microcirculation; Muscle; Neurotransmitter Agents – Metabolism; perfusion; Purinergic Agents/*metabolism; Signal Transduction; Skeletal – Blood Supply; Skeletal/*blood supply; Ultrasonography – Methods; Ultrasonography/*methods
BACKGROUND: Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signaling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. METHODS: Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1.3 MHz, mechanical index 1.3) was performed for 10 minutes after intravenous injection of 2x10(8) lipid microbubbles. Microvascular perfusion was evaluated by low-power contrast ultrasound perfusion imaging. In vivo muscle ATP release and in vitro ATP release from endothelial cells or erythrocytes were assessed by a luciferin-luciferase assay. Purinergic signaling pathways were assessed by studying interventions that (1) accelerated ATP degradation; (2) inhibited P2Y receptors, adenosine receptors, or KATP channels; or (3) inhibited downstream signaling pathways involving endothelial nitric oxide synthase or prostanoid production (indomethacin). Augmentation in muscle perfusion by ultrasound cavitation was assessed in a proof-of-concept clinical trial in 12 subjects with stable sickle cell disease. RESULTS: Therapeutic ultrasound cavitation increased muscle perfusion by 7-fold in normal mice, reversed tissue ischemia for up to 24 hours in the murine model of peripheral artery disease, and doubled muscle perfusion in patients with sickle cell disease. Augmentation in flow extended well beyond the region of ultrasound exposure. Ultrasound cavitation produced an approximately 40-fold focal and sustained increase in ATP, the source of which included both endothelial cells and erythrocytes. Inhibitory studies indicated that ATP was a critical mediator of flow augmentation that acts primarily through either P2Y receptors or adenosine produced by ectonucleotidase activity. Combined indomethacin and inhibition of endothelial nitric oxide synthase abolished the effects of therapeutic ultrasound, indicating downstream signaling through both nitric oxide and prostaglandins. CONCLUSIONS: Therapeutic ultrasound using microbubble cavitation to increase muscle perfusion relies on shear-dependent increases in ATP, which can act through a diverse portfolio of purinergic signaling pathways. These events can reverse hindlimb ischemia in mice for \textgreater24 hours and increase muscle blood flow in patients with sickle cell disease. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01566890.
Belcik J Todd; Davidson Brian P; Xie Aris; Wu Melinda D; Yadava Mrinal; Qi Yue; Liang Sherry; Chon Chae Ryung; Ammi Azzdine Y; Field Joshua; Harmann Leanne; Chilian William M; Linden Joel; Lindner Jonathan R
Circulation
2017
2017-03
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<a href="http://doi.org/10.1161/CIRCULATIONAHA.116.024826" target="_blank" rel="noreferrer noopener">10.1161/CIRCULATIONAHA.116.024826</a>
Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation.
129 Strain; Animals; cardiac function; contrast echocardiography; Coronary Circulation/*physiology; Coronary Vessels/*metabolism; hydrogen peroxide; Inbred C57BL; ion channel; Knockout; Kv1.5 Potassium Channel/*physiology; Mice; Muscle; Smooth; Transgenic; transgenic mice; Vascular/*metabolism; vasodilation; Vasodilation/*physiology; voltage-gated potassium channels
RATIONALE: In the working heart, coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels (Kv), which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox-sensitive. OBJECTIVE: To determine the role of redox-sensitive Kv1.5 channels in coronary metabolic flow regulation. METHODS AND RESULTS: In mice (wild-type [WT], Kv1.5 null [Kv1.5(-/-)], and Kv1.5(-/-) and WT with inducible, smooth muscle-specific expression of Kv1.5 channels), we measured mean arterial pressure, myocardial blood flow, myocardial tissue oxygen tension, and ejection fraction before and after inducing cardiac stress with norepinephrine. Cardiac work was estimated as the product of mean arterial pressure and heart rate. Isolated arteries were studied to establish whether genetic alterations modified vascular reactivity. Despite higher levels of cardiac work in the Kv1.5(-/-) mice (versus WT mice at baseline and all doses of norepinephrine), myocardial blood flow was lower in Kv1.5(-/-) mice than in WT mice. At high levels of cardiac work, tissue oxygen tension dropped significantly along with ejection fraction. Expression of Kv1.5 channels in smooth muscle in the null background rescued this phenotype of impaired metabolic dilation. In isolated vessels from Kv1.5(-/-) mice, relaxation to H2O2 was impaired, but responses to adenosine and acetylcholine were normal compared with those from WT mice. CONCLUSIONS: Kv1.5 channels in vascular smooth muscle play a critical role in coupling myocardial blood flow to cardiac metabolism. Absence of these channels disassociates metabolism from flow, resulting in cardiac pump dysfunction and tissue hypoxia.
Ohanyan Vahagn; Yin Liya; Bardakjian Raffi; Kolz Christopher; Enrick Molly; Hakobyan Tatevik; Kmetz John; Bratz Ian; Luli Jordan; Nagane Masaki; Khan Nadeem; Hou Huagang; Kuppusamy Periannan; Graham Jacqueline; Fu Frances Kwan; Janota Danielle; Oyewumi Moses O; Logan Suzanna; Lindner Jonathan R; Chilian William M
Circulation research
2015
2015-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1161/CIRCRESAHA.115.306642" target="_blank" rel="noreferrer noopener">10.1161/CIRCRESAHA.115.306642</a>
Induction of vascular progenitor cells from endothelial cells stimulates coronary collateral growth.
*Collateral Circulation; *Coronary Circulation; Animal; Animals; Biomarkers/metabolism; Cell Differentiation; Cell Lineage; Cells; Coronary Occlusion/genetics/metabolism/pathology/physiopathology/*surgery; Coronary Vessels/metabolism/pathology/*physiopathology; Cultured; Developmental; Disease Models; Endothelial Cells/metabolism/pathology/*transplantation; Epigenesis; Gene Expression Profiling; Gene Expression Regulation; Genetic; Induced Pluripotent Stem Cells/metabolism/*transplantation; Mice; Muscle; Myocytes; Neovascularization; Physiologic; Rats; Regenerative Medicine/methods; Regional Blood Flow; Reverse Transcriptase Polymerase Chain Reaction; SCID; Smooth; Smooth Muscle/metabolism/pathology/*transplantation; Sprague-Dawley; Teratoma/metabolism/pathology; Time Factors; Transcription Factors/genetics/metabolism; Transduction; Vascular/metabolism/pathology/*physiopathology
RATIONALE: A well-developed coronary collateral circulation improves the morbidity and mortality of patients following an acute coronary occlusion. Although regenerative medicine has great potential in stimulating vascular growth in the heart, to date there have been mixed results, and the ideal cell type for this therapy has not been resolved. OBJECTIVE: To generate induced vascular progenitor cells (iVPCs) from endothelial cells, which can differentiate into vascular smooth muscle cells (VSMCs) or endothelial cells (ECs), and test their capability to stimulate coronary collateral growth. METHODS AND RESULTS: We reprogrammed rat ECs with the transcription factors Oct4, Klf4, Sox2, and c-Myc. A population of reprogrammed cells was derived that expressed pluripotent markers Oct4, SSEA-1, Rex1, and AP and hemangioblast markers CD133, Flk1, and c-kit. These cells were designated iVPCs because they remained committed to vascular lineage and could differentiate into vascular ECs and VSMCs in vitro. The iVPCs demonstrated better in vitro angiogenic potential (tube network on 2-dimensional culture, tube formation in growth factor reduced Matrigel) than native ECs. The risk of teratoma formation in iVPCs is also reduced in comparison with fully reprogrammed induced pluripotent stem cells (iPSCs). When iVPCs were implanted into myocardium, they engrafted into blood vessels and increased coronary collateral flow (microspheres) and improved cardiac function (echocardiography) better than iPSCs, mesenchymal stem cells, native ECs, and sham treatments. CONCLUSIONS: We conclude that iVPCs, generated by partially reprogramming ECs, are an ideal cell type for cell-based therapy designed to stimulate coronary collateral growth.
Yin Liya; Ohanyan Vahagn; Pung Yuh Fen; Delucia Angelo; Bailey Erin; Enrick Molly; Stevanov Kelly; Kolz Christopher L; Guarini Giacinta; Chilian William M
Circulation research
2012
2012-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1161/CIRCRESAHA.111.250126" target="_blank" rel="noreferrer noopener">10.1161/CIRCRESAHA.111.250126</a>
Pulmonary vascular protein sieving capability after exposure to high vascular pressures.
Animals; Barotrauma/physiopathology; Blood Pressure/physiology; Blood Proteins/chemistry/*metabolism; Chemical; Dogs; Electrophoresis; Hypertension; Lymph/cytology/metabolism; Male; Models; Muscle; Permeability; Polyacrylamide Gel; Pulmonary Circulation/*physiology; Pulmonary Edema/physiopathology; Pulmonary/*physiopathology; Smooth; Vascular/*physiology
We evaluated the ability of the canine in situ left lower lobe (LLL) vasculature to sieve endogenous plasma proteins of various molecular radii (34-124 A) after LLL arterial pressure had been transiently elevated to 23.8 +/- 0.9 (control group, n = 5) or 92.3 +/- 1.4 (SE) Torr (high-pressure group, n = 9) by restricting LLL venous outflow under conditions of constant flow. After LLL flow was returned to natural perfusion, left atrial pressure was elevated in step increments, and LLL lymph and blood samples were collected until filtration-independent lymph-to-plasma protein concentration ratios (CL/CP) were obtained. The osmotic reflection coefficients (sigma d) for total proteins and seven protein fractions (separated by gradient gel electrophoresis) were calculated. The average total protein sigma d of the high-pressure group [0.51 +/- 0.06 (SE)] was significantly lower than that of the control group (0.68 +/- 0.03). Several LLLs of the high-pressure group, however, exhibited normal sigma d's. Protein fraction CL/CP's decreased with increasing molecular radius in both groups, but the CL/CP-molecular radius relationship was displaced upward in the high-pressure group. Pore analysis suggested that the decreases in sigma d could be explained by increases in the fractional flow through a large-pore system.
Bosso F J; Maron M B; Pilati C F; Jarjoura D G
Journal of applied physiology (Bethesda, Md. : 1985)
1992
1992-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jappl.1992.73.1.50" target="_blank" rel="noreferrer noopener">10.1152/jappl.1992.73.1.50</a>
The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth.
*Collateral Circulation; *Coronary Circulation; *Energy Metabolism; *Neovascularization; angiogenesis; Animals; arteriogenesis; Coronary Vessels/metabolism; Humans; mitochondria; Mitochondria; Mitochondrial Proteins/metabolism; Muscle; Muscle/*metabolism; Myocytes; Oxidative Stress; Phenotype; Physiologic; Reactive Oxygen Species/*metabolism; redox-dependent signaling; Signal Transduction; Smooth; Smooth Muscle/*metabolism; Vascular/*metabolism
Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis.
Pung Yuh Fen; Sam Wai Johnn; Hardwick James P; Yin Liya; Ohanyan Vahagn; Logan Suzanna; Di Vincenzo Lola; Chilian William M
American journal of physiology. Heart and circulatory physiology
2013
2013-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpheart.00077.2013" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00077.2013</a>
Trivalent chromium inhibits TSP-1 expression, proliferation, and O-GlcNAc signaling in vascular smooth muscle cells in response to high glucose in vitro.
Aorta/drug effects/metabolism; Cell Proliferation/*drug effects/genetics; Cells; Chromium/*pharmacology; Cultured; Fructosephosphates/metabolism; Genetic/drug effects/genetics; Glucose/*metabolism; Glutamine/genetics; Glycosylation/drug effects; Hexosamines/metabolism; Humans; Hyperglycemia/metabolism; Muscle; Myocytes; N-Acetylglucosaminyltransferases/genetics; O-glycosylation; Promoter Regions; reactive oxygen species; Reactive Oxygen Species/metabolism; Signal Transduction/*drug effects/genetics; Smooth; Smooth Muscle/*drug effects/metabolism; Thrombospondin 1/*antagonists & inhibitors/genetics; thrombospondin-1; Transcription; trivalent chromium; vascular smooth muscle cells; Vascular/*drug effects/metabolism
Trivalent chromium (Cr(3+)) is a mineral nutrient reported to have beneficial effects in glycemic and cardiovascular health. In vitro and in vivo studies suggest that Cr(3+) supplementation reduces the atherogenic potential and lowers the risk of vascular inflammation in diabetes. However, effects of Cr(3+) in vascular cells under conditions of hyperglycemia, characteristic of diabetes, remain unknown. In the present study we show that a therapeutically relevant concentration of Cr(3+) (100 nM) significantly downregulates a potent proatherogenic matricellular protein, thrombospondin-1 (TSP-1), in human aortic smooth muscle cells (HASMC) stimulated with high glucose in vitro. Promoter-reporter assays reveal that this downregulation of TSP-1 expression by Cr(3+) occurs at the level of transcription. The inhibitory effects of Cr(3+) on
Ganguly Rituparna; Sahu Soumyadip; Chavez Ronaldo J; Raman Priya
American journal of physiology. Cell physiology
2015
2015-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpcell.00256.2014" target="_blank" rel="noreferrer noopener">10.1152/ajpcell.00256.2014</a>
Leptin augments recruitment of IRF-1 and CREB to thrombospondin-1 gene promoter in vascular smooth muscle cells in vitro.
*cAMP response element-binding protein; *interferon regulatory factor-1; *leptin; *thrombospondin-1; *transcription; *vascular smooth muscle cells; Binding Sites/genetics; Cells; Chromatin Immunoprecipitation/methods; Cultured; Cyclic AMP Response Element-Binding Protein/*metabolism; Gene Expression Regulation/genetics; Genetic/genetics; Humans; Interferon Regulatory Factor-1/*metabolism; Leptin/*metabolism; Muscle; Mutagenesis; Myocytes; Promoter Regions; Response Elements/genetics; Site-Directed/methods; Smooth; Smooth Muscle/*metabolism; Thrombospondin 1/*genetics/*metabolism; Transcription; Transcriptional Activation/genetics; Transfection/methods; Up-Regulation/genetics; Vascular/*metabolism
We previously reported that high pathophysiological concentrations of leptin, the adipocyte-secreted peptide, upregulate the expression of a potent proatherogenic matricellular protein, thrombospondin-1 (TSP-1), in vascular smooth muscle cells. Moreover, this regulation was found to occur at the level of transcription; however, the underlying molecular mechanisms remain unknown. The goal of the present study was to investigate the specific transcriptional mechanisms that mediate upregulation of TSP-1 expression by leptin. Primary human aortic smooth muscle cell cultures were transiently transfected with different TSP-1 gene (THBS1) promoter-linked luciferase reporter constructs, and luciferase activity in response to leptin (100 ng/ml) was assessed. We identified a long THBS1 promoter (-1270/+750) fragment with specific leptin response elements that are required for increased TSP-1 transcription by leptin. Promoter analyses, protein/DNA array and gel shift assays demonstrated activation and association of transcription factors, interferon regulatory factor-1 (IRF-1) and cAMP response element-binding protein (CREB), to the distal fragment of the THBS1 promoter in response to leptin. Supershift, chromatin immunoprecipitation, and coimmunoprecipitation assays revealed formation of a single complex between IRF-1 and CREB in response to leptin; importantly, recruitment of this complex to the THBS1 promoter mediated leptin-induced TSP-1 transcription. Finally, binding sequence decoy oligomer and site-directed mutagenesis revealed that regulatory elements for both IRF-1 (-1019 to -1016) and CREB (-1198 to -1195), specific to the distal THBS1 promoter, were required for leptin-induced TSP-1 transcription. Taken together, these findings demonstrate that leptin promotes a cooperative association between IRF-1 and CREB on the THBS1 promoter driving TSP-1 transcription in vascular smooth muscle cells.
Sahu Soumyadip; Ganguly Rituparna; Raman Priya
American journal of physiology. Cell physiology
2016
2016-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpcell.00068.2016" target="_blank" rel="noreferrer noopener">10.1152/ajpcell.00068.2016</a>
Upregulation of thrombospondin-1 expression by leptin in vascular smooth muscle cells via JAK2- and MAPK-dependent pathways.
Animals; Cell Movement/physiology; Cells; Cultured; Gene Expression Regulation/physiology; Humans; Inbred C57BL; Janus Kinase 2/*biosynthesis; Knockout; Leptin/*physiology; Male; MAP Kinase Signaling System/*physiology; Mice; Muscle; Myocytes; Smooth; Smooth Muscle/enzymology/metabolism; Thrombospondin 1/*biosynthesis; Up-Regulation/*physiology; Vascular/enzymology/*metabolism
Hyperleptinemia, characteristic of diabetes and a hallmark feature of human obesity, contributes to the increased risk of atherosclerotic complications. However, molecular mechanisms mediating leptin-induced atherogenesis and gene expression in vascular cells remain incompletely understood. Accumulating evidence documents a critical role of a potent antiangiogenic and proatherogenic matricellular protein, thrombospondin-1 (TSP-1), in atherosclerosis. Although previous studies reported elevated TSP-1 levels in both diabetic and obese patients and rodent models, there is no direct information on TSP-1 expression in vascular cells in response to leptin. In the present study, we show that leptin upregulates TSP-1 expression in cultured human aortic smooth muscle cells (HASMC) in vitro, and this increase occurs at the level of transcription, revealed by mRNA stability and TSP-1 promoter-reporter assays. Utilizing specific pharmacological inhibitors and siRNA approaches, we demonstrate that upregulation of TSP-1 expression by leptin is mediated by JAK2/ERK/JNK-dependent mechanisms. Furthermore, we report that while ERK and JNK are required for both the constitutive and leptin-induced expression of TSP-1, JAK-2 appears to be specifically involved in leptin-mediated TSP-1 upregulation. Finally, we found that increased HASMC migration and proliferation in response to leptin is significantly inhibited by a TSP-1 blocking antibody, thereby revealing the physiological significance of leptin-TSP-1 crosstalk. Taken together, these findings demonstrate, for the first time, that leptin has a direct regulatory effect on TSP-1 expression in HASMCs, underscoring a novel role of TSP-1 in hyperleptinemia-induced atherosclerotic complications.
Chavez Ronaldo J; Haney Rebecca M; Cuadra Rene H; Ganguly Rituparna; Adapala Ravi K; Thodeti Charles K; Raman Priya
American journal of physiology. Cell physiology
2012
2012-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpcell.00008.2012" target="_blank" rel="noreferrer noopener">10.1152/ajpcell.00008.2012</a>
The University of California Institute of Environmental Stress marathon field studies.
*Physical Endurance; *Running; 20th Century; Biomarkers/blood; Biomedical Research/*history; Body Temperature Regulation; California; Competitive Behavior; Exercise Tolerance; Fluid Shifts; historical article; History; Humans; marathon; Muscle; oxygen consumption; Oxygen Consumption; Physiology/*history; Recovery of Function; Skeletal/metabolism/*physiology; thermoregulation; Time Factors; Universities/*history
In 1973, the Institute of Environmental Stress of the University of California-Santa Barbara, under the direction of Steven M. Horvath, began a series of field and laboratory studies of marathon runners during competition. As one of Horvath's graduate students, many of these studies became part of my doctoral dissertation. The rationale for studying runners under race conditions was based on my belief as a marathoner that runners would push themselves much harder while competing than under simulated conditions in the laboratory. Horvath's ready support of the studies likely had its roots in his graduate training at the Harvard Fatigue Laboratory, a laboratory well known for its field studies of individuals working in extreme environments. This report describes the studies of 1973-1975, focusing on how the measurements were made and detailing the learning experiences of a new graduate student. In 1973, blood chemistry and fluid shifts were studied in six runners before and for 3 days after a race. This was the first modern study to systematically examine the recovery process. In 1974, oxygen consumption was measured every 3 mi. in two runners during the race. In 1975, rectal temperature and five skin temperatures were evaluated in the same two runners every 1.4 mi. of the race. The latter two studies were the first to make such measurements under race conditions. The Institute of Environmental Stress marathon studies demonstrated the possibility of making measurements during competition without disrupting performance, enhanced our understanding of human exercise capacity under competitive conditions, and provided new insight into the postrace recovery process.
Maron Michael B
Advances in physiology education
2014
2014-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/advan.00118.2013" target="_blank" rel="noreferrer noopener">10.1152/advan.00118.2013</a>
Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress.
*ammonia; *ATP; *cellular respiration; *cirrhosis; *mitochondria; *Oxidative Stress; *portacaval anastamosis; *reactive oxygen species; *skeletal muscle; Adenosine Triphosphate/metabolism; Aged; Animals; Cell Line; Cell Respiration; Creatine Kinase/metabolism; Female; Humans; Hyperammonemia/*metabolism; Liver Cirrhosis/metabolism; Male; Middle Aged; Mitochondria; Muscle; Muscle/*metabolism; Myosin Heavy Chains/metabolism; NAD/metabolism; Rats; Reactive Oxygen Species/metabolism; Skeletal/*metabolism; Sprague-Dawley; Thiobarbituric Acid Reactive Substances/metabolism
KEY POINTS: Hyperammonaemia occurs in hepatic, cardiac and pulmonary diseases with increased muscle concentration of ammonia. We found that ammonia results in reduced skeletal muscle mitochondrial respiration, electron transport chain complex I dysfunction, as well as lower NAD(+) /NADH ratio and ATP content. During hyperammonaemia, leak of electrons from complex III results in oxidative modification of proteins and lipids. Tricarboxylic acid cycle intermediates are decreased during hyperammonaemia, and providing a cell-permeable ester of alphaKG reversed the lower TCA cycle intermediate concentrations and increased ATP content. Our observations have high clinical relevance given the potential for novel approaches to reverse skeletal muscle ammonia toxicity by targeting the TCA cycle intermediates and mitochondrial ROS. ABSTRACT: Ammonia is a cytotoxic metabolite that is removed primarily by hepatic ureagenesis in humans. Hyperammonaemia occurs in advanced hepatic, cardiac and pulmonary disease, and in urea cycle enzyme deficiencies. Increased skeletal muscle ammonia uptake and metabolism are the major mechanism of non-hepatic ammonia disposal. Non-hepatic ammonia disposal occurs in the mitochondria via glutamate synthesis from alpha-ketoglutarate resulting in cataplerosis. We show skeletal muscle mitochondrial dysfunction during hyperammonaemia in a comprehensive array of human, rodent and cellular models. ATP synthesis, oxygen consumption, generation of reactive oxygen species with oxidative stress, and tricarboxylic acid (TCA) cycle intermediates were quantified. ATP content was lower in the skeletal muscle from cirrhotic patients, hyperammonaemic portacaval anastomosis rat, and C2C12 myotubes compared to appropriate controls. Hyperammonaemia in C2C12 myotubes resulted in impaired intact cell respiration, reduced complex I/NADH oxidase activity and electron leak occurring at complex III of the electron transport chain. Consistently, lower NAD(+) /NADH ratio was observed during hyperammonaemia with reduced TCA cycle intermediates compared to controls. Generation of reactive oxygen species resulted in increased content of skeletal muscle carbonylated proteins and thiobarbituric acid reactive substances during hyperammonaemia. A cell-permeable ester of alpha-ketoglutarate reversed the low TCA cycle intermediates and ATP content in myotubes during hyperammonaemia. However, the mitochondrial antioxidant MitoTEMPO did not reverse the lower ATP content during hyperammonaemia. We provide for the first time evidence that skeletal muscle hyperammonaemia results in mitochondrial dysfunction and oxidative stress. Use of anaplerotic substrates to reverse ammonia-induced mitochondrial dysfunction is a novel therapeutic approach.
Davuluri Gangarao; Allawy Allawy; Thapaliya Samjhana; Rennison Julie H; Singh Dharmvir; Kumar Avinash; Sandlers Yana; Van Wagoner David R; Flask Chris A; Hoppel Charles; Kasumov Takhar; Dasarathy Srinivasan
The Journal of physiology
2016
2016-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1113/JP272796" target="_blank" rel="noreferrer noopener">10.1113/JP272796</a>
Flight feather attachment in rock pigeons (Columba livia): covert feathers and smooth muscle coordinate a morphing wing.
*avian; *covert feathers; *flight feathers; *quill knobs; *smooth muscle; *wing shape; Animal/*anatomy & histology; Animal/*physiology; Animals; Bone and Bones/anatomy & histology; Columbidae/*anatomy & histology; Feathers/*anatomy & histology; Flight; Muscle; Smooth/*anatomy & histology; Wings; X-Ray Microtomography
Mechanisms for passively coordinating forelimb movements and flight feather abduction and adduction have been described separately from both in vivo and ex vivo studies. Skeletal coordination has been identified as a way for birds to simplify the neuromotor task of controlling flight stroke, but an understanding of the relationship between skeletal coordination and the coordination of the aerodynamic control surface (the flight feathers) has been slow to materialize. This break between the biomechanical and aerodynamic approaches - between skeletal kinematics and airfoil shape - has hindered the study of dynamic flight behaviors. Here I use dissection and histology to identify previously overlooked interconnections between musculoskeletal elements and flight feathers. Many of these structures are well-placed to directly link elements of the passive musculoskeletal coordination system with flight feather movements. Small bundles of smooth muscle form prominent connections between upper forearm coverts (deck feathers) and the ulna, as well as the majority of interconnections between major flight feathers of the hand. Abundant smooth muscle may play a role in efficient maintenance of folded wing posture, and may also provide an autonomically regulated means of tuning wing shape and aeroelastic behavior in flight. The pattern of muscular and ligamentous linkages of flight feathers to underlying muscle and bone may provide predictable passive guidance for the shape of the airfoil during flight stroke. The structures described here provide an anatomical touchstone for in vivo experimental tests of wing surface coordination in an extensively researched avian model species.
Hieronymus Tobin L
Journal of anatomy
2016
2016-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/joa.12511" target="_blank" rel="noreferrer noopener">10.1111/joa.12511</a>
Calcium channel blocker toxicity.
Adult; Assisted Circulation; Calcium Channel Blockers/classification/pharmacokinetics/*poisoning; Calcium Channels; Calcium Chloride/therapeutic use; Cardiovascular Agents/therapeutic use; Cardiovascular Diseases/*chemically induced/drug therapy; Charcoal/therapeutic use; Child; Combined Modality Therapy; Drug Overdose/drug therapy/therapy; Enema; Extracorporeal Circulation; Fat Emulsions; Fluid Therapy; Glucagon/therapeutic use; Heart/drug effects; Humans; Hyperglycemia/*chemically induced/drug therapy; Infant; Intravenous/therapeutic use; L-Type/physiology; Muscle; Plasmapheresis; Poisoning/drug therapy/physiopathology/therapy; Practice Guidelines as Topic; Preschool; Smooth; Vascular/drug effects
Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.
Arroyo Anna Maria; Kao Louise W
Pediatric emergency care
2009
2009-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/PEC.0b013e3181b0a504" target="_blank" rel="noreferrer noopener">10.1097/PEC.0b013e3181b0a504</a>
Thrombospondin-4 mediates TGF-beta-induced angiogenesis.
Angiogenesis Inducing Agents/*metabolism; Animals; Cell Movement/drug effects; Cell Proliferation/drug effects; Cells; Chick Embryo; Cultured; Endothelium; Female; Gene Expression Regulation/drug effects; Humans; Inbred C57BL; Male; Mice; Muscle; Neovascularization; Pathologic/drug therapy/metabolism/*pathology; Signal Transduction/drug effects; Smooth; Thrombospondins/*physiology; Transforming Growth Factor beta/*pharmacology; Vascular/drug effects/metabolism/*pathology
TGF-beta is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the consequences of TGF-beta signaling are process-and stage-dependent, and it is not uncommon that TGF-beta exerts distinct and sometimes opposing effects on a disease progression depending on the stage and on the pathological changes associated with the stage. The mechanisms underlying cell- and process-specific effects of TGF-beta are poorly understood. We are describing a novel pathway that mediates induction of angiogenesis in response to TGF-beta1. We found that in endothelial cells (EC) thrombospondin-4 (TSP-4), a secreted extracellular matrix (ECM) protein, is upregulated in response to TGF-beta1 and mediates the effects of TGF-beta1 on angiogenesis. Upregulation of TSP-4 does not require the synthesis of new protein, is not caused by decreased secretion of
Muppala S; Xiao R; Krukovets I; Verbovetsky D; Yendamuri R; Habib N; Raman P; Plow E; Stenina-Adognravi O
Oncogene
2017
2017-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1038/onc.2017.140" target="_blank" rel="noreferrer noopener">10.1038/onc.2017.140</a>
Repair of distal biceps brachii tendon ruptures.
*Tendon Injuries/*surgery; Adult; Arm Injuries/surgery; Biomechanical Phenomena; Humans; Male; Middle Aged; Muscle; Orthopedic Procedures/methods; Retrospective Studies; Rupture; Skeletal/*injuries/surgery; Tendons/surgery; Treatment Outcome
This study consisted of 26 male patients with distal biceps tendon ruptures, 2 of whom had bilateral injuries, making the total number of ruptures 28. The average age at injury was 45 years. The treatment groups were the following: 3 were treated without surgery, 4 were repaired with brachialis tenodesis, and 21 were reattached to the radial tuberosity by the 2-incision Boyd-Anderson approach. Patients underwent follow-up a minimum of 14 months after surgery, with the average being 43 months. Outcome was evaluated based on the physical examination, isokinetic testing of strength and endurance of flexion and supination, and radiographic analysis.
Bell R H; Wiley W B; Noble J S; Kuczynski D J
Journal of shoulder and elbow surgery
2000
2000-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s1058-2746(00)90059-4" target="_blank" rel="noreferrer noopener">10.1016/s1058-2746(00)90059-4</a>
Why adult mammalian intrafusal and extrafusal fibers contain different myosin heavy-chain isoforms.
*Muscle Development; Afferent Pathways/physiology; Aging/metabolism; Animals; Cell Lineage; Developmental; Fetal Proteins/metabolism; Gene Expression Regulation; Knockout; Mammals/anatomy & histology/*metabolism; Mice; Morphogenesis; Muscle; Muscle Contraction; Muscle Fibers; Muscle Proteins/deficiency/physiology; Muscle Spindles/physiology; Myosin Heavy Chains/*metabolism; Nerve Tissue Proteins/deficiency/physiology; Protein Isoforms/*metabolism; Rats; Skeletal/*chemistry/classification; Skeletal/chemistry/embryology/*growth & development/ultrastructure; Transgenic
Multiple isoforms of the contractile protein myosin are present in mammalian skeletal muscles. The diversity of the heavy-chain subunits of myosin (MyHCs) in intrafusal fibers is thought to reflect a pathway of differentiation that is unique to muscle spindles. In fact, intrafusal MyHCs are developmental isoforms expressed by the prenatal precursors of both intrafusal and extrafusal fibers. In adult limbs, developmental MyHCs persist in intrafusal, but not extrafusal fibers principally due to the afferent neurons that arrest their maturational replacement by MyHCs associated with faster shortening velocities. The slow shortening velocities that are characteristic of developmental MyHCs might be adaptive for precise calibration of muscle spindles as sense organs.
Walro J M; Kucera J
Trends in neurosciences
1999
1999-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0166-2236(98)01339-3" target="_blank" rel="noreferrer noopener">10.1016/s0166-2236(98)01339-3</a>
Constant set points for pH and P(CO2) in cold-submerged skin-breathing frogs.
*Hydrogen-Ion Concentration; *Skin Physiological Phenomena; Acclimatization; Animals; Carbon Dioxide/blood/*metabolism; Cold Temperature; Immersion; Muscle; Oxygen/*metabolism; Partial Pressure; Rana temporaria/*physiology; Seasons; Skeletal/physiology
The low temperatures encountered by overwintering frogs result in a large downregulation of metabolism and behaviour. However, little is known about acid-base regulation in the extreme cold, especially when frogs become exclusive skin-breathers during their winter submergence. Blood and muscle tissue acid-base parameters (pH, P(CO2), bicarbonate and lactic acid concentrations) were determined in submerged frogs exposed to a range of low temperatures (0.2-7 degrees C). At overwintering temperatures between T = 0.2 and 4 degrees C plasma pH and P(CO2) were maintained constant, whereas intracellular pH regulation resulted in larger pH-temperature slopes occurring in the presumably more active heart muscle (deltapH/deltaT = -0.0313) than in the gastrocnemius muscle (deltapH/deltaT = -0.00799). Although blood pH was not significantly affected by submergence between 0.2 and 4 degrees C (pH = 8.220-8.253), it declined in the 7 degrees C frogs (pH = 8.086), a decrease not linked to the recruitment of anaerobiosis. Plasma P(CO2) and pH in the cold appear to be regulated at constant levels, implying that cutaneous CO2 conductance in submerged frogs is adjusted within the range of overwintering temperatures. This is likely geared toward facilitating the uptake of oxygen under conditions of greater metabolic demand, however there remains the possibility that acid-base balance itself is maintained at a constant set point at the frog's natural overwintering temperatures.
Tattersall G J; Boutilier R G
Respiration physiology
1999
1999-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0034-5687(99)00073-0" target="_blank" rel="noreferrer noopener">10.1016/s0034-5687(99)00073-0</a>
Phosphatidylinositide 3-kinase regulates angiotensin II-induced cytosolic phospholipase A2 activity and growth in vascular smooth muscle cells.
Angiotensin II/*metabolism; Animals; Arachidonic Acid/metabolism; Arachidonic Acids/pharmacology; Blotting; Cells; Chromones/pharmacology; Cultured; Enzyme Inhibitors/pharmacology; Flavonoids/pharmacology; Group IV Phospholipases A2; Male; Mitogen-Activated Protein Kinases/metabolism; Morpholines/pharmacology; Muscle; Phosphatidylinositol 3-Kinases/*physiology; Phospholipases A/*metabolism; Phospholipases A2; Phosphorylation; Rats; Smooth; Sprague-Dawley; Vascular/drug effects/*growth & development; Western
Angiotensin (Ang) II via the AT(1) receptor acts as a mitogen in vascular smooth muscle cells (VSMC) through stimulation of multiple signaling mechanisms, including tyrosine kinases and mitogen-activated protein kinase (MAPK). In addition, cytosolic phospholipase A(2)(cPLA(2))-dependent release of arachidonic acid (AA) is linked to VSMC growth and we have reported that Ang II stimulates cPLA(2) activity via the AT(1) receptor. The coupling of Ang II to the activation of cPLA(2) appears to involve mechanisms both upstream and downstream of MAPK such that AA stimulates MAPK activity which phosphorylates cPLA(2) to further enhance AA release. However, the upstream mechanisms responsible for activation of cPLA(2) are not well-defined. One possibility includes phosphatidylinositide
Silfani Tonous N; Freeman Ernest J
Archives of biochemistry and biophysics
2002
2002-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/S0003-9861(02)00066-8" target="_blank" rel="noreferrer noopener">10.1016/S0003-9861(02)00066-8</a>
Low thigh muscle mass is associated with coronary artery stenosis among
*Computed Tomography Angiography; *Tomography; Aged; Atherosclerotic; Body Composition; Chi-Square Distribution; Coronary Angiography/*methods; Coronary Artery Disease/*diagnostic imaging/epidemiology/pathology; Coronary artery stenosis; Coronary atherosclerosis; Coronary Stenosis/*diagnostic imaging/epidemiology/pathology; Coronary Vessels/*diagnostic imaging/pathology; Cross-Sectional Studies; HIV Infections/diagnosis/*epidemiology; HIV-infection; Humans; Male; Middle Aged; Multivariate Analysis; Muscle; Muscle mass; Odds Ratio; Plaque; Predictive Value of Tests; Prevalence; Prospective Studies; Risk Factors; Sarcopenia; Sarcopenia/*diagnostic imaging/epidemiology/physiopathology; Skeletal/*diagnostic imaging/physiopathology; Thigh; United States/epidemiology; X-Ray Computed
BACKGROUND: HIV-infected individuals are at increased risk for both sarcopenia and cardiovascular disease. Whether an association between low muscle mass and subclinical coronary artery disease (CAD) exists, and if it is modified by HIV serostatus, are unknown. METHODS: We performed cross-sectional analysis of 513 male MACS participants (72% HIV-infected) who underwent mid-thigh computed tomography (CT) and non-contrast cardiac CT for coronary artery calcium (CAC) during 2010-2013. Of these, 379 also underwent coronary CT angiography for non-calcified coronary plaque (NCP) and obstructive coronary stenosis \textgreater/=50%. Multivariable-adjusted Poisson regression was used to estimate prevalence risk ratios of associations between low muscle mass (\textless20th percentile of the
Tibuakuu Martin; Zhao Di; Saxena Ankita; Brown Todd T; Jacobson Lisa P; Palella Frank J Jr; Witt Mallory D; Koletar Susan L; Margolick Joseph B; Guallar Eliseo; Korada Sai Krishna C; Budoff Matthew J; Post Wendy S; Michos Erin D
Journal of cardiovascular computed tomography
2018
2018-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jcct.2018.01.007" target="_blank" rel="noreferrer noopener">10.1016/j.jcct.2018.01.007</a>
Effects of bariatric surgery on inflammatory, functional and structural markers of coronary atherosclerosis.
*Gastric Bypass; Adult; Biological Markers – Blood; Biomarkers/blood; Blood Flow Velocity – Physiology; Blood Flow Velocity/physiology; Blood Vessels – Pathology; Body Mass Index; Brachial Artery – Ultrasonography; Brachial Artery/diagnostic imaging; C-Reactive Protein – Analysis; C-Reactive Protein/analysis; Carotid Arteries – Pathology; Carotid Arteries/pathology; Cholesterol – Blood; Cholesterol/blood; Coronary Arteriosclerosis – Blood; Coronary Arteriosclerosis – Pathology; Coronary Arteriosclerosis – Physiopathology; Coronary Artery Disease/*blood/pathology/*physiopathology; Female; Follow-Up Studies; Gastric Bypass; Human; Humans; Male; Muscle; Prospective Studies; Smooth – Pathology; Triglycerides – Blood; Triglycerides/blood; Tunica Intima/pathology; Tunica Media/pathology; Ultrasonography; Vasodilation – Physiology; Vasodilation/physiology
This study was designed to assess the effects of bariatric weight loss surgery on structural, functional, and inflammatory markers of coronary atherosclerosis. Obesity is a worldwide epidemic and an independent risk factor for coronary atherosclerosis. It remains unclear whether surgically induced weight loss reduces cardiovascular risk. This prospective study enrolled 50 consecutive subjects with morbid obesity who underwent Roux-en-Y gastric bypass surgery (GBS) after failed attempts at medical weight loss. Subjects were recruited through a comprehensive weight loss center affiliated with an academic tertiary care hospital. All subjects had body mass indexes \textgreater or =40 kg/m(2) or body mass indexes of 35 to 40 kg/m(2) with \textgreater or =2 co-morbid obesity-related conditions. Markers of coronary atherosclerosis, including brachial artery flow-mediated dilation, carotid intima-media thickness, and high-sensitivity C-reactive protein, were measured before GBS and 6, 12, and 24 months after GBS. There were statistically significant improvements in all measured markers of coronary atherosclerosis after GBS. The mean body mass index decreased from 47 to 29.5 kg/m(2) at 24 months (p \textless0.001), the mean carotid intima-media thickness regressed from 0.84 to 0.50 mm at 24 months (p \textless0.001), mean flow-mediated dilation improved from 6.0% to 14.9% at 24 months (p \textless0.05), and mean high-sensitivity C-reactive protein decreased from 1.23 to 0.65 mg/dl at 6 months (p \textless0.001) and to 0.35 mg/dl at 24 months (p \textless0.001). In conclusion, GBS results in significant improvements in inflammatory, structural, and functional markers of coronary atherosclerosis.
Habib Phillip; Scrocco John David; Terek Megan; Vanek Vincent; Mikolich J Ronald
The American journal of cardiology
2009
2009-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.amjcard.2009.06.042" target="_blank" rel="noreferrer noopener">10.1016/j.amjcard.2009.06.042</a>
Sex differences in nitric oxide-mediated attenuation of vascular reactivity to vasopressin are abolished by gonadectomy.
*Orchiectomy; *Ovariectomy; Acetylcholine/pharmacology; Animals; Aorta; Arginine/analogs & derivatives/pharmacology; Female; In Vitro Techniques; Male; Muscle; Muscle Contraction/drug effects; Nitric Oxide/antagonists & inhibitors/*physiology; omega-N-Methylarginine; Phenylephrine/pharmacology; Potassium Chloride/pharmacology; Rats; Sex Characteristics; Smooth; Sprague-Dawley; Thoracic/drug effects/physiology; Vascular/drug effects/*physiology; Vasopressins/*pharmacology
In the rat thoracic aorta, contractile responses to vasopressin are two-fold higher in females than in males, primarily because nitric oxide-mediated attenuation of contraction is greater in males than in females. To determine the role of the gonadal steroids in this phenomenon, the effects of gonadectomy on nitric oxide and vascular reactivity to vasopressin were examined in thoracic aortae of age-matched intact and gonadectomized male and female rats. Maximal response to vasopressin was markedly higher in gonadectomized-male than in intact-male aortae (2729 +/- 421 vs. 1375 +/- 222 mg/mg ring weight; P \textless 0.01). Inhibition of nitric oxide synthase with NG-methyl-L-arginine (L-NMMA, 250 microM) enhanced maximal response of intact-male (2824 +/- 413 mg/mg ring weight; P \textless 0.01) but not gonadectomized-male aortae (3034 +/- 365 mg/mg ring weight; P \textgreater 0.05). Sensitivity of male aortae to vasopressin was unaffected by gonadectomy or
Stallone J N
European journal of pharmacology
1994
1994-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(94)90654-8" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(94)90654-8</a>