Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation

Background and objectivesAge and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation.Design, setting, participants, & measurementsIn total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis. For statistical analysis, mean comparison and multiple regression tests were used.ResultsIn patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy.ConclusionsIn this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy.Clinical Trial registration numbers:NCT02794142 and NCT02040363.

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Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice

Infection and Immunity ◽

10.1128/iai.01497-15 ◽

2016 ◽

Vol 84 (4) ◽

pp. 1123-1136 ◽

Cited By ~ 6

Author(s):

Ester Roffê ◽

Ana Paula M. P. Marino ◽

Joseph Weaver ◽

Wuzhou Wan ◽

Fernanda F. de Araújo ◽

...

Keyword(s):

Skeletal Muscle ◽

Trypanosoma Cruzi ◽

Acute Infection ◽

Chronic Inflammatory Disease ◽

Interleukin 17 ◽

Type I ◽

Necrotizing Vasculitis ◽

Necrosis Factor Alpha ◽

Content Type ◽

Inflammatory Monocytes

Infectious agents are often considered potential triggers of chronic inflammatory disease, including autoimmunity; however, direct evidence is usually lacking. Here we show that following control of acute infection of mice with the myotropic Colombiana strain ofTrypanosoma cruzi, parasites persisted in tissue at low levels associated with development of systemic necrotizing vasculitis. Lesions occurred in many but not all organs and tissues, with skeletal muscle arteries being the most severely affected, and were associated with myositis, atrophy, paresis/paralysis, and death. Histopathology showed fibrinoid vascular necrosis, rare amastigote nests within skeletal muscle myocytes, and massive leukocyte infiltrates composed mainly of inflammatory monocytes, F4/80+macrophages, andT. cruzitetramer-specific CD8+T lymphocytes capable of producing gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) but not interleukin-17 (IL-17).T. cruzi-specific IgG was detected in sera from infected mice, but antibody deposits and neutrophilic inflammation were not features of the lesions. Thus,T. cruziinfection of mice may be a specific infectious trigger of paralyzing systemic necrotizing vasculitis most severely affecting skeletal muscle, driven by pathogen-specific type I immune responses.

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Loss of quadriceps muscle oxidative phenotype and decreased endurance in patients with mild-to-moderate COPD

Journal of Applied Physiology ◽

10.1152/japplphysiol.00508.2012 ◽

2013 ◽

Vol 114 (9) ◽

pp. 1319-1328 ◽

Cited By ~ 61

Author(s):

Bram van den Borst ◽

Ilse G. M. Slot ◽

Valéry A. C. V. Hellwig ◽

Bettine A. H. Vosse ◽

Marco C. J. M. Kelders ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Skeletal Muscle ◽

Fiber Type ◽

Airflow Obstruction ◽

Quadriceps Muscle ◽

Activity Level ◽

Load Test ◽

Type I ◽

Oxidative Phenotype

Being well-established in advanced chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction and its underlying pathology have been scarcely investigated in patients with mild-to-moderate airflow obstruction. We hypothesized that a loss of oxidative phenotype (oxphen) associated with decreased endurance is present in the skeletal muscle of patients with mild-to-moderate COPD. In quadriceps muscle biopsies from 29 patients with COPD (forced expiratory volume in 1 s [FEV1] 58 ± 16%pred, body mass index [BMI] 26 ± 4 kg/m2) and 15 controls (BMI 25 ± 3 kg/m2) we assessed fiber type distribution, fiber cross-sectional areas (CSA), oxidative and glycolytic gene expression, OXPHOS protein levels, metabolic enzyme activity, and levels of oxidative stress markers. Quadriceps function was assessed by isokinetic dynamometry, body composition by dual-energy X-ray absorptiometry, exercise capacity by an incremental load test, and physical activity level by accelerometry. Compared with controls, patients had comparable fat-free mass index, quadriceps strength, and fiber CSA, but quadriceps endurance was decreased by 29% ( P = 0.002). Patients with COPD had a clear loss of muscle oxphen: a fiber type I-to-II shift, decreased levels of OXPHOS complexes IV and V subunits (47% and 31%, respectively; P < 0.05), a decreased ratio of 3-hydroxyacyl-CoA dehydrogenase/phosphofructokinase (PFK) enzyme activities (38%, P < 0.05), and decreased peroxisome proliferator-activated receptor-γ coactivator-1α (40%; P < 0.001) vs. increased PFK (67%; P < 0.001) gene expression levels. Within the patient group, markers of oxphen were significantly positively correlated with quadriceps endurance and inversely with the increase in plasma lactate relative to work rate during the incremental test. Levels of protein carbonylation, tyrosine nitration, and malondialdehyde protein adducts were comparable between patients and controls. However, among patients, oxidative stress levels were significantly inversely correlated with markers of oxphen and quadriceps endurance. Reduced muscle endurance associated with underlying loss of muscle oxphen is already present in patients with mild-to-moderate COPD without muscle wasting.

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Invited Review: Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.1.345 ◽

2001 ◽

Vol 90 (1) ◽

pp. 345-357 ◽

Cited By ~ 170

Author(s):

Kenneth M. Baldwin ◽

Fadia Haddad

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Motor Proteins ◽

Weight Bearing ◽

Activity Level ◽

Type I ◽

Mechanical Stimuli ◽

Energy Deprivation

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T3, 3,5,3′-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T3/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the β-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T3 or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T3 and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.

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Taguchi versus Lich-Grégoir Extravesical Ureteroneocystostomy in Kidney Transplantation: A Systematic Review

Urologia Internationalis ◽

10.1159/000518979 ◽

2021 ◽

pp. 1-9

Author(s):

Hannah Wehner ◽

Bernd Wullich ◽

Frank Kunath ◽

Hendrik Apel

Keyword(s):

Kidney Transplantation ◽

Prospective Studies ◽

Risk Of Bias ◽

Cochrane Library ◽

Confounding Factors ◽

Bladder Tissue ◽

Randomized Controlled ◽

Long Term Follow Up

Introduction: Ureteric implantation of the transplanted ureter into native urinary bladder tissue in kidney transplantation recipients is essential for post-operative kidney function. We aimed to determine the effects of Taguchi versus Lich-Grégoir extravesical ureteroneocystostomy in kidney transplantation. Methods: We searched multiple databases (MEDLINE, Cochrane Library, and Web of Science), trial registries, and conference proceedings until March 2021. We included prospective studies comparing Taguchi and Lich-Grégoir ureteroneocystostomy in kidney transplantation. Two review authors independently screened the identified records, extracted data, evaluated the risk of bias using ROBINS-I, and assessed the certainty of evidence according to GRADE. Results: We identified 3 prospective studies with serious or critical risk of bias, leading to low-certainty evidence. We downgraded the risk of bias due to study limitations. Assessment and/or reporting of baseline imbalances, co-interventions, and confounding factors was insufficient in all included studies. The effect of Taguchi ureteroneocystostomy remains unclear. Conclusion: Currently available evidence is not useful to determine the effect of Taguchi versus Lich-Grégoir ureteroneocystostomy in kidney transplantation. There is a need for methodologically better designed and executed studies, such as randomized controlled trials with long-term follow-up reporting baseline imbalances, co-interventions, and confounding factors.

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Canine diaphragm muscle after 1 yr of continuous electrical stimulation: its potential as a myocardial substitute

Journal of Applied Physiology ◽

10.1152/jappl.1987.62.3.1264 ◽

1987 ◽

Vol 62 (3) ◽

pp. 1264-1270 ◽

Cited By ~ 44

Author(s):

M. A. Acker ◽

J. D. Mannion ◽

W. E. Brown ◽

S. Salmons ◽

J. Henriksson ◽

...

Keyword(s):

Skeletal Muscle ◽

Fiber Type ◽

Diaphragm Muscle ◽

Type I ◽

Normal Heart ◽

Chronic Stimulation ◽

Normal Heart Rate ◽

Type Composition ◽

Long Term Changes

Skeletal muscle has been rendered fatigue resistant by chronic stimulation and therefore has potential as an active substitute for damaged myocardium. It is therefore important to know whether stimulation produces any deleterious effects in the long term. Hemidiaphragm muscles of four dogs were examined after chronic stimulation for 1 yr at either 2 or 4 Hz. The stimulated hemidiaphragms appeared normal on gross inspection and were still contracting vigorously. By histochemical and immunohistochemical criteria, they had acquired a uniformly type I character, in contrast to the mixed fiber type composition of the unstimulated hemidiaphragms. This transformation was also reflected in their complement of myosin isozymes. There was some enzymatic evidence of an associated shift towards aerobic pathways of energy generation. Histological examination revealed no evidence of degenerative changes. Trends, observed in the shorter term (6–8 wk), toward a decrease in fiber area and an increase in connective tissue showed no further progression at 1 yr. Thus hemidiaphragm muscle stimulated at frequencies at or above the normal heart rate does not appear to undergo adverse long-term changes that would constrain its use in a myocardial assist role.

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Surveillance of Carbapenem-Resistant Klebsiella pneumoniae: Tracking Molecular Epidemiology and Outcomes through a Regional Network

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02636-14 ◽

2014 ◽

Vol 58 (7) ◽

pp. 4035-4041 ◽

Cited By ~ 80

Author(s):

David van Duin ◽

Federico Perez ◽

Susan D. Rudin ◽

Eric Cober ◽

Jennifer Hanrahan ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Long Term Care ◽

Carbapenem Resistance ◽

The United States ◽

Molecular Characteristics ◽

Regional Network ◽

Term Care ◽

Content Type ◽

Carbapenem Resistant

ABSTRACTCarbapenem resistance in Gram-negative bacteria is on the rise in the United States. A regional network was established to study microbiological and genetic determinants of clinical outcomes in hospitalized patients with carbapenem-resistant (CR)Klebsiella pneumoniaein a prospective, multicenter, observational study. To this end, predefined clinical characteristics and outcomes were recorded andK. pneumoniaeisolates were analyzed for strain typing and resistance mechanism determination. In a 14-month period, 251 patients were included. While most of the patients were admitted from long-term care settings, 28% of them were admitted from home. Hospitalizations were prolonged and complicated. Nonsusceptibility to colistin and tigecycline occurred in isolates from 7 and 45% of the patients, respectively. Most of the CRK. pneumoniaeisolates belonged to repetitive extragenic palindromic PCR (rep-PCR) types A and B (both sequence type 258) and carried eitherblaKPC-2(48%) orblaKPC-3(51%). One isolate tested positive forblaNDM-1, a sentinel discovery in this region. Important differences between strain types were noted; rep-PCR type B strains were associated withblaKPC-3(odds ratio [OR], 294; 95% confidence interval [CI], 58 to 2,552;P< 0.001), gentamicin nonsusceptibility (OR, 24; 95% CI, 8.39 to 79.38;P< 0.001), amikacin susceptibility (OR, 11.0; 95% CI, 3.21 to 42.42;P< 0.001), tigecycline nonsusceptibility (OR, 5.34; 95% CI, 1.30 to 36.41;P= 0.018), a shorter length of stay (OR, 0.98; 95% CI, 0.95 to 1.00;P= 0.043), and admission from a skilled-nursing facility (OR, 3.09; 95% CI, 1.26 to 8.08;P= 0.013). Our analysis shows that (i) CRK. pneumoniaeis seen primarily in the elderly long-term care population and that (ii) regional monitoring of CRK. pneumoniaereveals insights into molecular characteristics. This work highlights the crucial role of ongoing surveillance of carbapenem resistance determinants.

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LONG-TERM SURVIVAL FOLLOWING KIDNEY TRANSPLANTATION IN 100 TYPE I DIABETIC PATIENTS

Transplantation Journal ◽

10.1097/00007890-198901000-00024 ◽

1989 ◽

Vol 47 (1) ◽

pp. 106-112 ◽

Cited By ~ 73

Author(s):

John S. Najarian ◽

Dixon B. Kaufman ◽

David S. Fryd ◽

Lois McHugh ◽

S. Michael Mauer ◽

...

Keyword(s):

Kidney Transplantation ◽

Diabetic Patients ◽

Type I ◽

Term Survival ◽

Long Term Survival

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Skeletal Muscle Ratio: A Complete Mediator of Physical Activity and HbA1C in Type 2 Diabetes

Biological Research For Nursing ◽

10.1177/1099800420942884 ◽

2020 ◽

Vol 22 (4) ◽

pp. 536-543

Author(s):

Sen-Te Wang ◽

Yen-Kuang Lin ◽

Shuen-Fu Weng ◽

Chen-Ling Huang ◽

Hui-Chuan Huang ◽

...

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Visceral Fat ◽

Serum Glucose ◽

Activity Level ◽

Visceral Fat Area ◽

The Relationship

Background: An increase in the physical activity level reduces body weight, decreases body fat, increases skeletal muscle mass, and improves serum glucose; however, the influence of body composition parameters on the relationship between physical activity and serum glucose remains unclear. Objective: This study investigated whether skeletal muscle and visceral fat affect the relationship between high physical activity and long-term serum glucose goals. Method: This cross-sectional study recruited patients with type 2 diabetes. The Chinese version of the International Physical Activity Questionnaire was used for estimating the physical activity level, and a bioimpedance device was used to measure the skeletal muscle ratio (skeletal muscle mass/total body weight, %) and visceral fat area (cm2). Hierarchical logistic regression models and mediation tests were conducted according to Hayes’ procedures. Results: Of the total 543 Chinese individuals with type 2 diabetes enrolled, HbA1C levels of fewer than half (n = 243, 44.8%) met the target of ≤7.0%. The skeletal muscle ratio was found to be a complete mediator (OR = 0.920, 95% CI: 0.848 to 0.998; indirect effect: −0.238, 95% CI: −0.525 to −0.020) of the relationship between high physical activity and the target HbA1C level after controlling for visceral fat area (indirect effect: −0.013, 95% CI: −0.183 to 0.156), age, time since diabetes diagnosis, and rice intake. Conclusion: Nurses should include an increase in the skeletal muscle ratio as an objective in physical activity interventions for patients with type 2 diabetes to help them achieve their long-term serum glucose goals.

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Muscle-Specific PPARβ/δAgonism May Provide Synergistic Benefits with Life Style Modifications

PPAR Research ◽

10.1155/2007/30578 ◽

2007 ◽

Vol 2007 ◽

pp. 1-7

Author(s):

Adnan Erol

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Fiber Type ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Type I ◽

Peroxisome Proliferator Activated Receptor ◽

Targeted Expression

Peroxisome proliferator-activated receptorβ/δ(PPARβ/δ) has emerged as a powerful metabolic regulator in diverse tissues including fat, skeletal muscle, and the heart. It is now established that activation of PPARβ/δpromotes fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. In muscle, PPARβ/δappears to act as a central regulator of fatty acid catabolism. PPARβ/δcontents are increased in muscle during physiological situations such as physical exercise or long-term fasting, characterized by increased fatty acid oxidation. Targeted expression of an activated form of PPARβ/δin skeletal muscle induces a switch to form increased numbers of type I muscle fibers resembling the fiber type transition by endurance training. Activation of PPARβ/δalso enhances mitochondrial capacity and fat oxidation in the skeletal muscle that resembles the effect of regular exercise. Therefore, it is hypothesized that muscle-specific PPARβ/δagonists could be a key strategy to support the poor cardiorespiratory fitness associated with metabolic disorders.

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Compound anterior cranial base fractures: classification using computerized tomography scanning as a basis for selection of patients for dural repair

Journal of Neurosurgery ◽

10.3171/jns.1998.88.3.0471 ◽

1998 ◽

Vol 88 (3) ◽

pp. 471-477 ◽

Cited By ~ 53

Author(s):

Damianos E. Sakas ◽

David J. Beale ◽

Ameen A. Ameen ◽

Helen L. Whitwell ◽

Karl W. Whittaker ◽

...

Keyword(s):

Computerized Tomography ◽

Cumulative Effect ◽

Ct Scanning ◽

Cranial Base ◽

Type I ◽

Csf Rhinorrhea ◽

Content Type ◽

Anterior Cranial Base ◽

Fine Print

Object. A classification is proposed to organize anterior cranial base fractures systematically according to their location and size. The goal of this study was to determine whether these two variables, irrespective of cerebrospinal fluid (CSF) rhinorrhea, are related to the long-term risk of posttraumatic meningitis and, hence, to standardize decision making concerning surgical repair of associated CSF fistulas. Methods. With the aid of high-resolution thin-section coronal computerized tomography (CT) scanning, anterior cranial base fractures were classified into the following four major types: I, cribriform; II, frontoethmoidal; III, lateral frontal; and IV, complex (any combination of the other three types). Fractures with a maximum bone displacement that extended farther than 1 cm in any plane were classified as “large” and those less than 1 cm as “small.” The authors used this classification in a study of 48 patients who were treated by conservative (20 patients) or surgical (28 patients) means. The results showed a gradation of risk: the fracture most likely to develop infection was a large cribriform (Type I) and the least likely was a small lateral frontal (Type III). Statistical analysis showed that the trend for an increased infection rate was related to the cumulative effect of three variables in the following order: 1) prolonged duration of rhinorrhea (analysis of variance [ANOVA], p = 0.017); 2) large size of fracture displacement (ANOVA, p = 0.079); and 3) fracture's proximity to the midline (ANOVA, p = 0.015). Conclusions. In this series, microsurgical repair was accompanied by a minimum complication rate. Hence, the authors recommend that patients with fractures that combine the aforementioned variables should be considered to have a high long-term risk of infection and their injury should be surgically repaired as soon as the posttraumatic edema has subsided. This applies to the following fractures: large cribriform (Type I) with transient rhinorrhea lasting 5 to 8 days and large frontoethmoidal (Type II) with prolonged rhinorrhea lasting longer than 8 days. Furthermore, the authors conclude that this classification can improve the management of posttraumatic CSF fistulas of the anterior cranial base and may provide insights into the mechanisms underlying their spontaneous repair and susceptibility to meningitis.

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