Histologically Measured Cardiomyocyte Hypertrophy Correlates with Body Height as Strongly as with Body Mass Index

Directory of Open Access Journals (Sweden)

Richard E. Tracy

2011-01-01

Full Text Available Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH. This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height2.7 as a proxy for lean body mass and body mass index (BMI as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally.

Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege–Potter syndrome

Directory of Open Access Journals (Sweden)

Andrew J. Degnan, MD, MPhil

2017-03-01

Full Text Available We report a rare case of metastatic malignant solitary fibrous tumor (SFT that presented with hypoglycemia because of insulin growth factor-2 production. Initial workup included computed tomography imaging that revealed a large, partially necrotic liver mass, a hypervascular pancreatic head lesion, and 2 renal lesions. Following hepatic resection, pancreatic head resection and nephrectomy, all these lesions demonstrated pathological findings that were consistent with SFT. The patient also had a history of an intracranial mass that had been previously resected and treated with gamma knife therapy at an outside institution, which was found to also be SFT. Six months after initial pancreatic head resection, the patient developed a new lesion involving the pancreatic tail that was found to represent recurrent metastatic SFT. This case emphasizes the highly aggressive nature of extrapleural SFT, while rare, and the role of imaging in follow-up for disease recurrence.

Periodontitis and myocardial hypertrophy.

Science.gov (United States)

Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

2017-04-01

There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

Protein timing and its effects on muscular hypertrophy and strength in individuals engaged in weight-training

Directory of Open Access Journals (Sweden)

Stark Matthew

2012-12-01

Full Text Available Abstract The purpose of this review was to determine whether past research provides conclusive evidence about the effects of type and timing of ingestion of specific sources of protein by those engaged in resistance weight training. Two essential, nutrition-related, tenets need to be followed by weightlifters to maximize muscle hypertrophy: the consumption of 1.2-2.0 g protein.kg -1 of body weight, and ≥44-50 kcal.kg-1 of body weight. Researchers have tested the effects of timing of protein supplement ingestion on various physical changes in weightlifters. In general, protein supplementation pre- and post-workout increases physical performance, training session recovery, lean body mass, muscle hypertrophy, and strength. Specific gains, differ however based on protein type and amounts. Studies on timing of consumption of milk have indicated that fat-free milk post-workout was effective in promoting increases in lean body mass, strength, muscle hypertrophy and decreases in body fat. The leucine content of a protein source has an impact on protein synthesis, and affects muscle hypertrophy. Consumption of 3–4 g of leucine is needed to promote maximum protein synthesis. An ideal supplement following resistance exercise should contain whey protein that provides at least 3 g of leucine per serving. A combination of a fast-acting carbohydrate source such as maltodextrin or glucose should be consumed with the protein source, as leucine cannot modulate protein synthesis as effectively without the presence of insulin. Such a supplement post-workout would be most effective in increasing muscle protein synthesis, resulting in greater muscle hypertrophy and strength. In contrast, the consumption of essential amino acids and dextrose appears to be most effective at evoking protein synthesis prior to rather than following resistance exercise. To further enhance muscle hypertrophy and strength, a resistance weight- training program of at least 10–12 weeks

Protein timing and its effects on muscular hypertrophy and strength in individuals engaged in weight-training

Science.gov (United States)

2012-01-01

The purpose of this review was to determine whether past research provides conclusive evidence about the effects of type and timing of ingestion of specific sources of protein by those engaged in resistance weight training. Two essential, nutrition-related, tenets need to be followed by weightlifters to maximize muscle hypertrophy: the consumption of 1.2-2.0 g protein.kg -1 of body weight, and ≥44-50 kcal.kg-1 of body weight. Researchers have tested the effects of timing of protein supplement ingestion on various physical changes in weightlifters. In general, protein supplementation pre- and post-workout increases physical performance, training session recovery, lean body mass, muscle hypertrophy, and strength. Specific gains, differ however based on protein type and amounts. Studies on timing of consumption of milk have indicated that fat-free milk post-workout was effective in promoting increases in lean body mass, strength, muscle hypertrophy and decreases in body fat. The leucine content of a protein source has an impact on protein synthesis, and affects muscle hypertrophy. Consumption of 3–4 g of leucine is needed to promote maximum protein synthesis. An ideal supplement following resistance exercise should contain whey protein that provides at least 3 g of leucine per serving. A combination of a fast-acting carbohydrate source such as maltodextrin or glucose should be consumed with the protein source, as leucine cannot modulate protein synthesis as effectively without the presence of insulin. Such a supplement post-workout would be most effective in increasing muscle protein synthesis, resulting in greater muscle hypertrophy and strength. In contrast, the consumption of essential amino acids and dextrose appears to be most effective at evoking protein synthesis prior to rather than following resistance exercise. To further enhance muscle hypertrophy and strength, a resistance weight- training program of at least 10–12 weeks with compound movements for

Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series

International Nuclear Information System (INIS)

Tonoli, Sandro; Vitali, Paola; Scotti, Vieri; Bertoni, Filippo; Spiazzi, Luigi; Ghedi, Barbara; Buonamici, Fabrizio Banci; Marrazzo, Livia; Guidi, Gabriele; Meattini, Icro; Bastiani, Paolo; Amichetti, Maurizio; Schwarz, Marco; Magrini, Stefano Maria

2011-01-01

Background and purpose: To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena). Material and methods: Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases. Results: Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively. Conclusion: Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP.

Proton Therapy for Malignant Pleural Mesothelioma After Extrapleural Pleuropneumonectomy

International Nuclear Information System (INIS)

Krayenbuehl, Jerome; Hartmann, Matthias; Lomax, Anthony J.

2010-01-01

Purpose: To perform comparative planning for intensity-modulated radiotherapy (IMRT) and proton therapy (PT) for malignant pleural mesothelioma after radical surgery. Methods and Materials: Eight patients treated with IMRT after extrapleural pleuropneumonectomy (EPP) were replanned for PT, comparing dose homogeneity, target volume coverage, and mean and maximal dose to organs at risk. Feasibility of PT was evaluated regarding the dose distribution with respect to air cavities after EPP. Results: Dose coverage and dose homogeneity of the planning target volume (PTV) were significantly better for PT than for IMRT regarding the volume covered by >95% (V95) for the high-dose PTV. The mean dose to the contralateral kidney, ipsilateral kidney, contralateral lung, liver, and heart and spinal cord dose were significantly reduced with PT compared with IMRT. After EPP, air cavities were common (range, 0-850 cm 3 ), decreasing from 0 to 18.5 cm 3 /day. In 2 patients, air cavity changes during RT decreased the generalized equivalent uniform dose (gEUD) in the case of using an a value of < - 10 to the PTV2 to <2 Gy in the presence of changing cavities for PT, and to 40 Gy for IMRT. Small changes were observed for gEUD of PTV1 because PTV1 was reached by the beams before air. Conclusion: Both PT and IMRT achieved good target coverage and dose homogeneity. Proton therapy accomplished additional dose sparing of most organs at risk compared with IMRT. Proton therapy dose distributions were more susceptible to changing air cavities, emphasizing the need for adaptive RT and replanning.

Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

Science.gov (United States)

Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

2018-04-01

The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet.

Science.gov (United States)

Viana Gonçalves, Igor Cândido; Cerdeira, Cláudio Daniel; Poletti Camara, Eduardo; Dias Garcia, José Antônio; Ribeiro Pereira Lima Brigagão, Maísa; Bessa Veloso Silva, Roberta; Bitencourt Dos Santos, Gérsika

2017-09-01

Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice. Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed. A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group. In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

[Progress of midfacial fat compartments and related clinical applications].

Science.gov (United States)

Wen, Lihong; Wang, Jinhuang; Li, Yang; Liu, Dalie

2018-02-01

To review the research progress of midfacial fat compartments, and to thoroughly understand its current state of the anatomy and the aging morphologic characters of midfacial fat compartments, as well as the current status of clinical applications. The recent literature concerning the midfacial fat compartments and related clinical applications were extensively reviewed and analyzed. Midfacial fat layer has been considered as a fusion and a continuous layer, experiencing a global atrophy when aging. As more anatomical researches have done, recent studies have shown that midfacial fat layer is broadly divided into superficial and deep layers, which are both divided into different fat compartments by fascia, ligaments, or muscles. Midfacial fat compartments tend to atrophy with age, specifically in the deep fat compartments while hypertrophy in the superficial fat compartments. Clinical applications show that fat volumetric restoration with deep medial cheek fat and Ristow's space can restore the appearance of midface effectively. In recent years, the researches of midfacial fat compartments have achieved obvious progress, which will provide new ideas and basis for fat volumetric restoration. Corresponding treatments are selected based on different sites and different layers with different aging changes, reshaping a more youthful midface.

Global Transcriptomic Profiling of Cardiac Hypertrophy and Fatty Heart Induced by Long-Term High-Energy Diet in Bama Miniature Pigs.

Directory of Open Access Journals (Sweden)

Jihan Xia

Full Text Available A long-term high-energy diet affects human health and leads to obesity and metabolic syndrome in addition to cardiac steatosis and hypertrophy. Ectopic fat accumulation in the heart has been demonstrated to be a risk factor for heart disorders, but the molecular mechanism of heart disease remains largely unknown. Bama miniature pigs were fed a high-fat, high-sucrose diet (HFHSD for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased body weight (2.73-fold, P<0.01, insulin level (4.60-fold, P<0.01, heart weight (1.82-fold, P<0.05 and heart volume (1.60-fold, P<0.05 compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. Microarray analyses revealed that 1,022 genes were significantly differentially expressed (P<0.05, ≥1.5-fold change, including 591 up-regulated and 431 down-regulated genes in the HFHSD group relative to the control group. KEGG analysis indicated that the observed heart disorder involved the signal transduction-related MAPK, cytokine, and PPAR signaling pathways, energy metabolism-related fatty acid and oxidative phosphorylation signaling pathways, heart function signaling-related focal adhesion, axon guidance, hypertrophic cardiomyopathy and actin cytoskeleton signaling pathways, inflammation and apoptosis pathways, and others. Quantitative RT-PCR assays identified several important differentially expressed heart-related genes, including STAT3, ACSL4, ATF4, FADD, PPP3CA, CD74, SLA-8, VCL, ACTN2 and FGFR1, which may be targets of further research. This study shows that a long-term, high-energy diet induces obesity, cardiac steatosis, and hypertrophy and provides insights into the molecular mechanisms of hypertrophy and fatty heart to facilitate further research.

The effects of knee immobilization on marrow adipocyte hyperplasia and hypertrophy at the proximal rat tibia epiphysis.

Science.gov (United States)

Trudel, Guy; Uhthoff, Hans K; Solanki, Sanjay; Laneuville, Odette

2017-09-01

Marrow adipose deposition is observed during aging and in association with extended periods of immobility. The objective of this study was to determine the contribution of adipocyte hypertrophy and hyperplasia to bone marrow fat deposition induced by immobilization of the rat knee joint for 2, 4, 16 or 32 weeks. Histomorphometric analyses compared immobilized to sham-operated proximal tibia from age and gender matched rats to assess the contribution of aging and duration of immobilization on the number and size of marrow adipocytes. Results indicated that marrow adipose tissue increased with the duration of immobilization and was significant larger at 16 weeks compared to the sham-operated group (0.09956±0.13276mm 2 vs 0.01990±0.01100mm 2 , p=0.047). The marrow adipose tissue was characterized by hyperplasia of adipocytes with a smaller average size after 2 and 4 weeks of immobilization (at 2 weeks hyperplasia: 68.86±33.62 vs 43.57±24.47 adipocytes/mm 2 , p=0.048; at 4 weeks hypotrophy: 0.00036±0.00019 vs 0.00046±0.00023mm 2 , p=0.027), and by adipocyte hypertrophy after 16 weeks of immobilization (0.00083±0.00049 vs 0.00046±0.00028mm 2 , p=0.027) compared to sham-operated. Both immobilized and sham-operated groups showed marrow adipose conversion with age; immobilized (p=0.008; sham: p=0.003). Overall, fat deposition in the bone marrow of the proximal rat tibia epiphysis and induced by knee joint immobilization was characterized by hyperplasia of small adipocytes in the early phase and by adipocyte hypertrophy in the later phase. Mediators of marrow fat deposition after immobilization and preventive countermeasures need to be investigated. Copyright © 2017 Elsevier GmbH. All rights reserved.

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

Science.gov (United States)

Gao, Mingming; Ma, Yongjie; Liu, Dexi

2015-01-01

High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

Science.gov (United States)

Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

2015-01-01

In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

[Asymmetric hypertrophy of the masticatory muscles].

Science.gov (United States)

Arzul, L; Corre, P; Khonsari, R H; Mercier, J-M; Piot, B

2012-06-01

Hypertrophy of the masticatory muscles most commonly affects the masseter. Less common cases of isolated or associated temporalis hypertrophy are also reported. Parafunctional habits, and more precisely bruxism, can favor the onset of the hypertrophy. This condition is generally idiopathic and can require both medical and/or surgical management. A 29-year-old patient was referred to our department for an asymmetric swelling of the masticatory muscles. Physical examination revealed a bilateral hypertrophy of the masticatory muscles, predominantly affecting the right temporalis and the left masseter. Major bruxism was assessed by premature dental wearing. The additional examinations confirmed the isolated muscle hypertrophy. Benign asymmetric hypertrophy of the masticatory muscles promoted by bruxism was diagnosed. Treatment with injections of type A botulinum toxin was conducted in association with a splint and relaxation. Its effectiveness has been observed at six months. Few cases of unilateral or bilateral temporalis hypertrophy have been reported, added to the more common isolated masseter muscles hypertrophy. The diagnosis requires to rule out secondary hypertrophies and tumors using Magnetic Resonance Imaging. The condition is thought to be favoured by parafunctional habits such as bruxism. The conservative treatment consists in reducing the volume of the masticatory muscles using intramuscular injections of type A botulinum toxin. Other potential conservative treatments are wearing splints and muscle relaxant drugs. Surgical procedures aiming to reduce the muscle volume and/or the bone volume (mandibular gonioplasty) can be proposed. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

Directory of Open Access Journals (Sweden)

Mingming Gao

Full Text Available High-fat diet (HFD has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

β-Hydroxy-β-methylbutyrate (HMβ supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway

Directory of Open Access Journals (Sweden)

Pimentel Gustavo D

2011-02-01

Full Text Available Abstract β-Hydroxy-β-methylbutyrate (HMβ supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e.g., fat and liver have not been examined. The purpose of this study was to evaluate the effects of HMβ supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HMβ (320 mg/kg body weight or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HMβ supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HMβ supplementation can be used to increase muscle mass without adverse health effects.

Genetics Home Reference: myostatin-related muscle hypertrophy

Science.gov (United States)

... Twitter Home Health Conditions Myostatin-related muscle hypertrophy Myostatin-related muscle hypertrophy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Myostatin-related muscle hypertrophy is a rare condition characterized ...

Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion.

Science.gov (United States)

Balogun, Kayode A; Cheema, Sukhinder K

2016-01-01

Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)-3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n-3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi-purified diets (20 % w/w fat) containing high n-3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n-3 PUFA (10 % w/w), medium n-3 PUFA (4 % w/w), or low n-3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase-2 (DGAT-2), fatty acid binding protein-4 (FABP-4) and leptin were measured. The high n-3 PUFA group showed higher levels of total n-3 PUFA in gonadal TAG compared to the medium and low n-3 PUFA groups (P < 0.001). The high n-3 PUFA male group had a lower adipocyte area compared to the medium and low n-3 PUFA group (P < 0.001); however, no difference was observed in females. The high n-3 PUFA male group showed lower mRNA expression of FABP-4, DGAT-2 and leptin compared to the low n-3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n-3 PUFA group compared to the other groups. Our findings show for the first time that n-3 PUFA prevents adipocyte hypertrophy by downregulating FABP-4, DGAT-2 and leptin; the effects are however sex-specific.

Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

Science.gov (United States)

Ianuzzo, C. D.; Chen, V.

1977-01-01

Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

Directory of Open Access Journals (Sweden)

J. Rodríguez-Castelán

2017-01-01

Full Text Available Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT. Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C. In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits.

Science.gov (United States)

Rodríguez-Castelán, J; Méndez-Tepepa, M; Carrillo-Portillo, Y; Anaya-Hernández, A; Rodríguez-Antolín, J; Zambrano, E; Castelán, F; Cuevas-Romero, E

2017-01-01

Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

Compensative hypertrophy of the kidney

International Nuclear Information System (INIS)

Raynaud, C.

1976-01-01

Several measurement methods are available to practitioners to reveal a compensative hypertrophy. Mensuration of the kidney has the advantage of simplicity but is in fact an unreliable and inaccurate method. Separate clearances in their traditional form have never entered into routine use because of the disadvantages of ureteral catheterism. The use of radioactive tracers avoids this drawback, but clearances calculated in this way are only valid in the absence of obstructive urinary disorders. Solutions have been proposed, but the values obtained are no longer identical with the clearances. The Hg uptake test quantifies quite accurately the function of each kidney. From the results obtained a complete compensative hypertrophy developed on a healthy kidney and an incomplete compensative hypertrophy developed on the diseased kidney have been described. In each of these situations the degree to which compensative hypertrophy develops seems to be fixed at a given level peculiar to each patient [fr

Trehalose prevents adipocyte hypertrophy and mitigates insulin resistance.

Science.gov (United States)

Arai, Chikako; Arai, Norie; Mizote, Akiko; Kohno, Keizo; Iwaki, Kanso; Hanaya, Toshiharu; Arai, Shigeyuki; Ushio, Simpei; Fukuda, Shigeharu

2010-12-01

Trehalose has been shown to evoke lower insulin secretion than glucose in oral saccharide tolerance tests in humans. Given this hypoinsulinemic effect of trehalose, we hypothesized that trehalose suppresses adipocyte hypertrophy by reducing storage of triglyceride and mitigates insulin resistance in mice fed a high-fat diet (HFD). Mice were fed an HFD and given drinking water containing 2.5% saccharide (glucose [Glc], trehalose [Tre], maltose [Mal], high-fructose corn syrup, or fructose [Fru]) ad libitum. After 7 weeks of HFD and saccharide intake, fasting serum insulin levels in the Tre/HFD group were significantly lower than in the Mal/HFD and Glc/HFD groups (P fructose corn syrup/HFD, or Fru/HFD group. Analysis of gene expression in mesenteric adipocytes showed that no statistically significant difference in the expression of monocyte chemoattractant protein-1 (MCP-1) messenger RNA (mRNA) was observed between the Tre/HFD group and the distilled water/standard diet group, whereas a significant increase in the MCP-1 mRNA expression was observed in the Glc/HFD, Mal/HFD, Fru/HFD, and distilled water/HFD groups. Thus, our data indicate that trehalose prevents adipocyte hypertrophy and mitigates insulin resistance in HFD-fed mice by reducing insulin secretion and down-regulating mRNA expression of MCP-1. These findings further suggest that trehalose is a functional saccharide that mitigates insulin resistance. Copyright © 2010 Elsevier Inc. All rights reserved.

Apical cap

International Nuclear Information System (INIS)

McLoud, T.C.; Isler, R.J.; Novelline, R.A.; Putman, C.E.; Simeone, J.; Stark, P.

1981-01-01

Apical caps, either unilateral or bilateral, are a common feature of advancing age and are usually the result of subpleural scarring unassociated with other diseases. Pancoast (superior sulcus) tumors are a well recognized cause of unilateral asymmetric apical density. Other lesions arising in the lung, pleura, or extrapleural space may produce unilateral or bilateral apical caps. These include: (1) inflammatory: tuberculosis and extrapleural abscesses extending from the neck; (2) post radiation fibrosis after mantle therapy for Hodgkin disease or supraclavicular radiation in the treatment of breast carcinoma; (3) neoplasm: lymphoma extending from the neck or mediastinum, superior sulcus bronchogenic carcinoma, and metastases; (4) traumatic: extrapleural dissection of blood from a ruptured aorta, fractures of the ribs or spine, or hemorrhage due to subclavian line placement; (5) vascular: coarctation of the aorta with dilated collaterals over the apex, fistula between the subclavian artery and vein; and (6) miscellaneous: mediastinal lipomatosis with subcostal fat extending over the apices

Gender and post-ischemic recovery of hypertrophied rat hearts

Directory of Open Access Journals (Sweden)

Popov Kirill M

2006-03-01

Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

The role of satellite cells in muscle hypertrophy.

Science.gov (United States)

Blaauw, Bert; Reggiani, Carlo

2014-02-01

The role of satellite cells in muscle hypertrophy has long been a debated issue. In the late 1980s it was shown that proteins remain close to the myonucleus responsible for its synthesis, giving rise to the idea of a nuclear domain. This, together with the observation that during various models of muscle hypertrophy there is an activation of the muscle stem cells, i.e. satellite cells, lead to the idea that satellite cell activation is required for muscle hypertrophy. Thus, satellite cells are not only responsible for muscle repair and regeneration, but also for hypertrophic growth. Further support for this line of thinking was obtained after studies showing that irradiation of skeletal muscle, and therefore elimination of all satellite cells, completely prevented overload-induced hypertrophy. Recently however, using different transgenic approaches, it has become clear that muscle hypertrophy can occur without a contribution of satellite cells, even though in most situations of muscle hypertrophy satellite cells are activated. In this review we will discuss the contribution of satellite cells, and other muscle-resident stem cells, to muscle hypertrophy both in mice as well as in humans.

Raf-mediated cardiac hypertrophy in adult Drosophila

Directory of Open Access Journals (Sweden)

Lin Yu

2013-07-01

In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

Science.gov (United States)

Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

2012-01-01

Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

A Systems Biology Approach to Investigating Sex Differences in Cardiac Hypertrophy.

Science.gov (United States)

Harrington, Josephine; Fillmore, Natasha; Gao, Shouguo; Yang, Yanqin; Zhang, Xue; Liu, Poching; Stoehr, Andrea; Chen, Ye; Springer, Danielle; Zhu, Jun; Wang, Xujing; Murphy, Elizabeth

2017-08-19

Heart failure preceded by hypertrophy is a leading cause of death, and sex differences in hypertrophy are well known, although the basis for these sex differences is poorly understood. This study used a systems biology approach to investigate mechanisms underlying sex differences in cardiac hypertrophy. Male and female mice were treated for 2 and 3 weeks with angiotensin II to induce hypertrophy. Sex differences in cardiac hypertrophy were apparent after 3 weeks of treatment. RNA sequencing was performed on hearts, and sex differences in mRNA expression at baseline and following hypertrophy were observed, as well as within-sex differences between baseline and hypertrophy. Sex differences in mRNA were substantial at baseline and reduced somewhat with hypertrophy, as the mRNA differences induced by hypertrophy tended to overwhelm the sex differences. We performed an integrative analysis to identify mRNA networks that were differentially regulated in the 2 sexes by hypertrophy and obtained a network centered on PPARα (peroxisome proliferator-activated receptor α). Mouse experiments further showed that acute inhibition of PPARα blocked sex differences in the development of hypertrophy. The data in this study suggest that PPARα is involved in the sex-dimorphic regulation of cardiac hypertrophy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Postural control in women with breast hypertrophy

Directory of Open Access Journals (Sweden)

Alessandra Ferreira Barbosa

2012-07-01

Full Text Available OBJECTIVES: The consequences of breast hypertrophy have been described based on the alteration of body mass distribution, leading to an impact on psychological and physical aspects. The principles of motor control suggest that breast hypertrophy can lead to sensorimotor alterations and the impairment of body balance due to postural misalignment. The aim of this study is to evaluate the postural control of women with breast hypertrophy under different sensory information conditions. METHOD: This cross-sectional study included 14 women with breast hypertrophy and 14 without breast hypertrophy, and the mean ages of the groups were 39 ±15 years and 39±16 years, respectively. A force platform was used to assess the sensory systems that contribute to postural control: somatosensory, visual and vestibular. Four postural conditions were sequentially tested: eyes open and fixed platform, eyes closed and fixed platform, eyes open and mobile platform, and eyes closed and mobile platform. The data were processed, and variables related to the center of pressure were analyzed for each condition. The Kruskal-Wallis test was used to compare the conditions between the groups for the area of center of pressure displacement and the velocity of center of pressure displacement in the anterior-posterior and medial-lateral directions. The alpha level error was set at 0.05. RESULTS: Women with breast hypertrophy presented an area that was significantly higher for three out of four conditions and a higher velocity of center of pressure displacement in the anterior-posterior direction under two conditions: eyes open and mobile platform and eyes closed and mobile platform. CONCLUSIONS: Women with breast hypertrophy have altered postural control, which was demonstrated by the higher area and velocity of center of pressure displacement.

Hypoxia, Oxidative Stress and Fat

Directory of Open Access Journals (Sweden)

Nikolaus Netzer

2015-06-01

Full Text Available Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators.

Mechanisms for altered carnitine content in hypertrophied rat hearts

International Nuclear Information System (INIS)

Reibel, D.K.; O'Rourke, B.; Foster, K.A.

1987-01-01

Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-[ 14 C]carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by ∼20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels

Altered carnitine transport in pressure-overload hypertrophied rat hearts

International Nuclear Information System (INIS)

O'Rourke, B.; Foster, K.; Reibel, D.K.

1986-01-01

The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L- 14 C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 μM carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 μM carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart

Comparative Analyses between Skeletal Muscle miRNAomes from Large White and Min Pigs Revealed MicroRNAs Associated with Postnatal Muscle Hypertrophy.

Science.gov (United States)

Sheng, Xihui; Wang, Ligang; Ni, Hemin; Wang, Lixian; Qi, Xiaolong; Xing, Shuhan; Guo, Yong

2016-01-01

The molecular mechanism regulated by microRNAs (miRNAs) that underlies postnatal hypertrophy of skeletal muscle is complex and remains unclear. Here, the miRNAomes of longissimus dorsi muscle collected at five postnatal stages (60, 120, 150, 180, and 210 days after birth) from Large White (commercial breed) and Min pigs (indigenous breed of China) were analyzed by Illumina sequencing. We identified 734 miRNAs comprising 308 annotated miRNAs and 426 novel miRNAs, of which 307 could be considered pig-specific. Comparative analysis between two breeds suggested that 60 and 120 days after birth were important stages for skeletal muscle hypertrophy and intramuscular fat accumulation. A total of 263 miRNAs were significantly differentially expressed between two breeds at one or more developmental stages. In addition, the differentially expressed miRNAs between every two adjacent developmental stages in each breed were determined. Notably, ssc-miR-204 was significantly more highly expressed in Min pig skeletal muscle at all postnatal stages compared with its expression in Large White pig skeletal muscle. Based on gene ontology and KEGG pathway analyses of its predicted target genes, we concluded that ssc-miR-204 may exert an impact on postnatal hypertrophy of skeletal muscle by regulating myoblast proliferation. The results of this study will help in elucidating the mechanism underlying postnatal hypertrophy of skeletal muscle modulated by miRNAs, which could provide valuable information for improvement of pork quality and human myopathy.

Isolated unilateral temporalis muscle hypertrophy in a child: a case report with literature review

OpenAIRE

Ranasinghe, Jagath C.; Wickramasinghe, Chandani; Rodrigo, Ganganath

2018-01-01

Background Temporalis muscle hypertrophy is a rare entity of masticatory muscle hypertrophy. All types of masticatory muscle hypertrophies have been documented of which temporalis muscle hypertrophy is one. Temporalis muscle hypertrophy is most commonly bilateral and usually associated with other types of masticatory muscles hypertrophy such as masseter or pterygoid hypertrophy. However, isolated unilateral temporalis muscle hypertrophy is extremely rare and only 9 cases have been reported to...

Effects of Yogurt Containing Fermented Pepper Juice on the Body Fat and Cholesterol Level in High Fat and High Cholesterol Diet Fed Rat.

Science.gov (United States)

Yeon, Su-Jung; Hong, Go-Eun; Kim, Chang-Kyu; Park, Woo Joon; Kim, Soo-Ki; Lee, Chi-Ho

2015-01-01

This experiment investigated whether yogurt containing fermented pepper juice (FPJY) affects cholesterol level in high fat and high cholesterol diet (HFCD) fed rat. Twenty five Sprague-Dawley male rats of 7 wk were divided into 5 groups, and fed following diets for 9 wk; CON (control diet), HFCD (HFCD), PY (HFCD supplemented with 2% of plain yogurt), LFY (HFCD supplemented with 2% of FPJY), and HFY (HFCD supplemented with 5% of FPJY). In the LFY group, hepatic total lipid level decreased significantly compared to the HFCD group (p0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (p0.05). Liver weight decreased as FPJY content was increased. Results suggested FPJY would inhibit organ hypertrophy and accumulation of body fat, hepatic lipid, and cholesterol in HFCD fed rat.

Muscle hypertrophy as the presenting sign in a patient with a complete FHL1 deletion.

Science.gov (United States)

Willis, T A; Wood, C L; Hudson, J; Polvikoski, T; Barresi, R; Lochmüller, H; Bushby, K; Straub, V

2016-08-01

Four and a half LIM protein 1 (FHL1/SLIM1) has recently been identified as the causative gene mutated in four distinct diseases affecting skeletal muscle that have overlapping features, including reducing body myopathy, X-linked myopathy, X-linked dominant scapuloperoneal myopathy and Emery-Dreifuss muscular dystrophy. FHL1 localises to the sarcomere and the sarcolemma and is believed to participate in muscle growth and differentiation as well as in sarcomere assembly. We describe in this case report a boy with a deletion of the entire FHL1 gene who is now 15 years of age and presented with muscle hypertrophy, reduced subcutaneous fat, rigid spine and short stature. This case is the first, to our knowledge, with a complete loss of the FHL1 protein and MAP7D3 in combination. It supports the theory that dominant negative effects (accumulation of cytotoxic-mutated FHL1 protein) worsen the pathogenesis. It extends the phenotype of FHL1-related myopathies and should prompt future testing in undiagnosed patients who present with unexplained muscle hypertrophy, contractures and rigid spine, particularly if male. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy

Directory of Open Access Journals (Sweden)

Xiaoqiang Yao

2017-04-01

Full Text Available Cardiac hypertrophy is a major risk factor for heart failure, which are among the leading causes of human death. Gastrodin is a small molecule that has been used clinically to treat neurological and vascular diseases for many years without safety issues. In the present study, we examined protective effect of gastrodin against cardiac hypertrophy and explored the underlying mechanism. Phenylephrine and angiotensin II were used to induce cardiac hypertrophy in a mouse model and a cultured cardiomyocyte model. Gastrodin was found to alleviate the cardiac hypertrophy in both models. Mechanistically, gastrodin attenuated the store-operated Ca2+ entry (SOCE by reducing the expression of STIM1 and Orai1, two key proteins in SOCE, in animal models as well as in cultured cardiomyocyte model. Furthermore, suppressing SOCE by RO2959, Orai1-siRNAs or STIM1-siRNAs markedly attenuated the phenylephrine-induced hypertrophy in cultured cardiomyocyte model. Together, these results showed that gastrodin inhibited cardiac hypertrophy and it also reduced the SOCE via its action on the expression of STIM1 and Orai1. Furthermore, suppression of SOCE could reduce the phenylephrine-induced cardiomyocyte hypertrophy, suggesting that SOCE-STIM1-Orai1 is located upstream of hypertrophy.

Time course of gene expression during mouse skeletal muscle hypertrophy.

Science.gov (United States)

Chaillou, Thomas; Lee, Jonah D; England, Jonathan H; Esser, Karyn A; McCarthy, John J

2013-10-01

The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ≥2-fold increase or ≥50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy.

Neurogenic muscle hypertrophy in a 12-year-old girl.

Science.gov (United States)

Zutelija Fattorini, Matija; Gagro, Alenka; Dapic, Tomislav; Krakar, Goran; Marjanovic, Josip

2017-01-01

Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular hypertrophy.

Science.gov (United States)

Lanjewar, Swapnil S; Chhabra, Lovely; Chaubey, Vinod K; Joshi, Saurabh; Kulkarni, Ganesh; Kothagundla, Chandrasekhar; Kaul, Sudesh; Spodick, David H

2013-01-01

The electrocardiographic diagnostic dyad of emphysema, namely a combination of the frontal vertical P-vector and a narrow QRS duration, can serve as a quasidiagnostic marker for emphysema, with specificity close to 100%. We postulated that the presence of left ventricular hypertrophy in emphysema may affect the sensitivity of this electrocardiographic criterion given that left ventricular hypertrophy generates prominent left ventricular forces and may increase the QRS duration. We reviewed the electrocardiograms and echocardiograms for 73 patients with emphysema. The patients were divided into two groups based on the presence or absence of echocardiographic evidence of left ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume in one second (FEV1) were computed and compared between the two subgroups. There was no statistically significant difference in qualitative lung function (FEV1) between the subgroups. There was no statistically significant difference in mean P-vector between the subgroups. The mean QRS duration was significantly longer in patients with left ventricular hypertrophy as compared with those without left ventricular hypertrophy. The presence of left ventricular hypertrophy may not affect the sensitivity of the P-vector verticalization when used as a lone criterion for diagnosing emphysema. However, the presence of left ventricular hypertrophy may significantly reduce the sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it causes a widening of the QRS duration.

Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

Science.gov (United States)

Arai, Takeshi; Kim, Hyoun-ju; Hirako, Satoshi; Nakasatomi, Maki; Chiba, Hiroshige; Matsumoto, Akiyo

2013-01-01

We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.

Science.gov (United States)

Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye-Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

2015-08-01

Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

Muscle hypertrophy and fast fiber type conversions in heavy resistance-trained women.

Science.gov (United States)

Staron, R S; Malicky, E S; Leonardi, M J; Falkel, J E; Hagerman, F C; Dudley, G A

1990-01-01

Twenty-four women completed a 20-week heavy-resistance weight training program for the lower extremity. Workouts were twice a week and consisted of warm-up exercises followed by three sets each of full squats, vertical leg presses, leg extensions, and leg curls. All exercises were performed to failure using 6-8 RM (repetition maximum). Weight training caused a significant increase in maximal isotonic strength (1 RM) for each exercise. After training, there was a decrease in body fat percentage (p less than 0.05), and an increase in lean body mass (p less than 0.05) with no overall change in thigh girth. Biopsies were obtained before and after training from the superficial portion of the vastus lateralis muscle. Sections were prepared for histological and histochemical examination. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were distinguished following routine myofibrillar adenosine triphosphatase histochemistry. Areas were determined for fiber types I, IIA, and IIAB + IIB. The heavy-resistance training resulted in significant hypertrophy of all three groups: I (15%), IIA (45%), and IIAB + IIB (57%). These data are similar to those in men and suggest considerable hypertrophy of all major fiber types is also possible in women if exercise intensity and duration are sufficient. In addition, the training resulted in a significant decrease in the percentage of IIB with a concomitant increase in IIA fibers, suggesting that strength training may lead to fiber conversions.

Is Pleurectomy/Decortication Superior to Extrapleural Pneumonectomy for Patients with Malignant Pleural Mesothelioma? A Single-Institutional Experience.

Science.gov (United States)

Miyazaki, Takuro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Kamohara, Ryotaro; Hatachi, Go; Nagayasu, Takeshi

2018-04-20

This study was performed to compare the outcome of pleurectomy/decortication (P/D) with that of extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma (MPM). Patients with MPM underwent either P/D or EPP from August 2008 to December 2014. Various clinicopathological factors were analyzed to identify differences between the two procedures. P/D was performed in nine patients and EPP in 30 patients. Most of the patients' background characteristics were not significantly different between the groups. The surgery time (680 vs. 586 min, p = 0.0034) and bleeding volume (4050 vs. 2110 mL, p = 0.002) were significantly greater in P/D than in EPP; however, grade ≥3 complications (44% vs. 33%, p = 0.54) and length of postoperative hospital stay (29 vs. 37 days, p = 0.26) were not significantly different. The median survival time and 2- and 3-year survival rates in all patients were 16.7 months, 28.5%, and 15.3%, respectively. The median survival time and 2- and 3-year survival in the P/D and EPP groups were 22.5 months, 43.8%, and 43.8% and 16.5 months, 24.0%, and 14.4%, respectively (p = 0.13). Survival of patients with MPM remains poor despite multidisciplinary treatment. P/D is comparable with EPP and could be a safe and another surgical treatment for patients with MPM.

Fatty acid utilization in pressure-overload hypertrophied rat hearts

International Nuclear Information System (INIS)

Reibel, D.K.; O'Rourke, B.

1986-01-01

The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H 2 O left atrial filling pressure with a ventricular afterload of 80 cm of H 2 O with buffer containing 1.2 mM 14 C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. 14 CO 2 production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by 14 CO 2 production during this time was 0.728 +/- 0.06 μmoles/min/g dry in control hearts and 0.710 +/- 0.02 μmoles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O 2 consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 μmoles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine

Muscular and systemic correlates of resistance training-induced muscle hypertrophy.

Science.gov (United States)

Mitchell, Cameron J; Churchward-Venne, Tyler A; Bellamy, Leeann; Parise, Gianni; Baker, Steven K; Phillips, Stuart M

2013-01-01

To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH), insulin like grow factor 1 (IGF-1) and interleukin 6 (IL-6)], or intramuscular [skeletal muscle androgen receptor (AR) protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk. Muscle biopsies were obtained before and after the training period and acutely 1 and 5 h after the first training session. Serum hormones and cytokines were measured immediately, 15, 30 and 60 minutes following the first and last training sessions of the study. Mean fiber area increased by 20% (range: -7 to 80%; P<0.001). Protein content of the AR was unchanged with training (fold change = 1.17 ± 0.61; P=0.19); however, there was a significant correlation between the changes in AR content and fiber area (r=0.60, P=0.023). Phosphorylation of p70S6K was elevated 5 hours following exercise, which was correlated with gains in mean fiber area (r=0.54, P=0.007). There was no relationship between the magnitude of the pre- or post-training exercise-induced changes in free testosterone, GH, or IGF-1 concentration and muscle fiber hypertrophy; however, the magnitude of the post exercise IL-6 response was correlated with muscle hypertrophy (r=0.48, P=0.019). Post-exercise increases in circulating hormones are not related to hypertrophy following training. Exercise-induced changes in IL-6 correlated with hypertrophy, but the mechanism for the role of IL-6 in hypertrophy is not known. Acute increases, in p70S6K phosphorylation and changes in muscle AR protein content correlated with muscle hypertrophy implicating intramuscular rather than systemic processes in mediating hypertrophy.

Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular hypertrophy

Directory of Open Access Journals (Sweden)

Lanjewar SS

2013-11-01

Full Text Available Swapnil S Lanjewar,1 Lovely Chhabra,1 Vinod K Chaubey,1 Saurabh Joshi,1 Ganesh Kulkarni,1 Chandrasekhar Kothagundla,1 Sudesh Kaul,1 David H Spodick21Department of Internal Medicine, 2Department of Cardiovascular Medicine, Saint Vincent Hospital, University of Massachusetts Medical School, Worcester, MA, USABackground: The electrocardiographic diagnostic dyad of emphysema, namely a combination of the frontal vertical P-vector and a narrow QRS duration, can serve as a quasidiagnostic marker for emphysema, with specificity close to 100%. We postulated that the presence of left ventricular hypertrophy in emphysema may affect the sensitivity of this electrocardiographic criterion given that left ventricular hypertrophy generates prominent left ventricular forces and may increase the QRS duration.Methods: We reviewed the electrocardiograms and echocardiograms for 73 patients with emphysema. The patients were divided into two groups based on the presence or absence of echocardiographic evidence of left ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume in one second (FEV1 were computed and compared between the two subgroups.Results: There was no statistically significant difference in qualitative lung function (FEV1 between the subgroups. There was no statistically significant difference in mean P-vector between the subgroups. The mean QRS duration was significantly longer in patients with left ventricular hypertrophy as compared with those without left ventricular hypertrophy.Conclusion: The presence of left ventricular hypertrophy may not affect the sensitivity of the P-vector verticalization when used as a lone criterion for diagnosing emphysema. However, the presence of left ventricular hypertrophy may significantly reduce the sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it causes a widening of the QRS duration.Keywords: emphysema, electrocardiogram, left ventricular hypertrophy, chronic

Pharmacological targeting of CDK9 in cardiac hypertrophy.

Science.gov (United States)

Krystof, Vladimír; Chamrád, Ivo; Jorda, Radek; Kohoutek, Jirí

2010-07-01

Cardiac hypertrophy allows the heart to adapt to workload, but persistent or unphysiological stimulus can result in pump failure. Cardiac hypertrophy is characterized by an increase in the size of differentiated cardiac myocytes. At the molecular level, growth of cells is linked to intensive transcription and translation. Several cyclin-dependent kinases (CDKs) have been identified as principal regulators of transcription, and among these CDK9 is directly associated with cardiac hypertrophy. CDK9 phosphorylates the C-terminal domain of RNA polymerase II and thus stimulates the elongation phase of transcription. Chronic activation of CDK9 causes not only cardiac myocyte enlargement but also confers predisposition to heart failure. Due to the long interest of molecular oncologists and medicinal chemists in CDKs as potential targets of anticancer drugs, a portfolio of small-molecule inhibitors of CDK9 is available. Recent determination of CDK9's crystal structure now allows the development of selective inhibitors and their further optimization in terms of biochemical potency and selectivity. CDK9 may therefore constitute a novel target for drugs against cardiac hypertrophy.

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy.

Science.gov (United States)

White, James P; Wrann, Christiane D; Rao, Rajesh R; Nair, Sreekumaran K; Jedrychowski, Mark P; You, Jae-Sung; Martínez-Redondo, Vicente; Gygi, Steven P; Ruas, Jorge L; Hornberger, Troy A; Wu, Zhidan; Glass, David J; Piao, Xianhua; Spiegelman, Bruce M

2014-11-04

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.

Systematic review of the synergist muscle ablation model for compensatory hypertrophy.

Science.gov (United States)

Terena, Stella Maris Lins; Fernandes, Kristianne Porta Santos; Bussadori, Sandra Kalill; Deana, Alessandro Melo; Mesquita-Ferrari, Raquel Agnelli

2017-02-01

The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model. Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review. The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model. This model differs from other overload models (exercise and training) regarding the characteristics involved in the hypertrophy process (acute) and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.

Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

Directory of Open Access Journals (Sweden)

Slava Malatiali

2008-01-01

Full Text Available The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin and protein excretion rate (PER were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001, Cinulin increased 80% (P<.01. Kidney wet and dry weights increased 10%–12% (P<.05, and glomerular tuft area increased 9.3% (P<.001. Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.

Science.gov (United States)

Lin, Xue; Yang, Penghua; Reece, E Albert; Yang, Peixin

2017-08-01

Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The type 2 diabetes mellitus embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, desmin, and adrenomedullin. Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor, osteopontin, and galectin-3 genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic group. Maternal diabetes significantly increased β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and desmin expression, but decreased expression of adrenomedullin. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type 2 diabetes mellitus

Muscular and systemic correlates of resistance training-induced muscle hypertrophy.

Directory of Open Access Journals (Sweden)

Cameron J Mitchell

Full Text Available PURPOSE: To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH, insulin like grow factor 1 (IGF-1 and interleukin 6 (IL-6], or intramuscular [skeletal muscle androgen receptor (AR protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. METHODS: Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk. Muscle biopsies were obtained before and after the training period and acutely 1 and 5 h after the first training session. Serum hormones and cytokines were measured immediately, 15, 30 and 60 minutes following the first and last training sessions of the study. RESULTS: Mean fiber area increased by 20% (range: -7 to 80%; P<0.001. Protein content of the AR was unchanged with training (fold change = 1.17 ± 0.61; P=0.19; however, there was a significant correlation between the changes in AR content and fiber area (r=0.60, P=0.023. Phosphorylation of p70S6K was elevated 5 hours following exercise, which was correlated with gains in mean fiber area (r=0.54, P=0.007. There was no relationship between the magnitude of the pre- or post-training exercise-induced changes in free testosterone, GH, or IGF-1 concentration and muscle fiber hypertrophy; however, the magnitude of the post exercise IL-6 response was correlated with muscle hypertrophy (r=0.48, P=0.019. CONCLUSION: Post-exercise increases in circulating hormones are not related to hypertrophy following training. Exercise-induced changes in IL-6 correlated with hypertrophy, but the mechanism for the role of IL-6 in hypertrophy is not known. Acute increases, in p70S6K phosphorylation and changes in muscle AR protein content correlated with muscle hypertrophy implicating intramuscular rather than systemic processes in mediating hypertrophy.

Systematic review of the synergist muscle ablation model for compensatory hypertrophy

Directory of Open Access Journals (Sweden)

Stella Maris Lins Terena

Full Text Available Summary Objective: The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model. Method: Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review. Results: The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model. Conclusion: This model differs from other overload models (exercise and training regarding the characteristics involved in the hypertrophy process (acute and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.

Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-Induced hypertrophy.

Science.gov (United States)

Huang, Kun; Gao, Lu; Yang, Ming; Wang, Jiliang; Wang, Zheng; Wang, Lin; Wang, Guobin; Li, Huili

2017-08-01

Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed. We further explored the mechanism of CTSV cardioprotective by assessing the levels and activities of PI3K/Akt/mTOR and MAPK signaling pathway proteins. We found that pre-treating cardiomyocytes with CTSV could significantly inhibit Ang Ⅱ-induced hypertrophy. The mRNA expression of hypertrophy markers ANP, BNP and β-MHC was obviously elevated in Ang Ⅱ-treated cardiac cells. Whereas, exogenous CTSV effectively halted this elevation. Further study revealed that the protective effects of exogenous CTSV might be mediated by repressing the phosphorylation of proteins in the PI3K/Akt/mTOR and MAPK pathways. Based on our results, we concluded that exogenous CTSV inhibited Ang Ⅱ-induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR. This study provides experimental evidence for the application of CTSV protein for the treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Solving the cardiac hypertrophy riddle: The angiotensin II-mechanical stress connection.

Science.gov (United States)

Zablocki, Daniela; Sadoshima, Junichi

2013-11-08

A series of studies conducted 20 years ago, documenting the cardiac hypertrophy phenotype and its underlying signaling mechanism induced by angiotensin II (Ang II) and mechanical stress, showed a remarkable similarity between the effect of the Gαq agonist and that of mechanical forces on cardiac hypertrophy. Subsequent studies confirmed the involvement of autocrine/paracrine mechanisms, including stretch-induced release of Ang II in load-induced cardiac hypertrophy. Recent studies showed that the Ang II type 1 (AT1) receptor is also directly activated by mechanical forces, suggesting that AT1 receptors play an important role in mediating load-induced cardiac hypertrophy through both ligand- and mechanical stress-dependent mechanisms.

Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

Science.gov (United States)

Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

2016-01-01

Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population.

Science.gov (United States)

Atilla, Mahmut Huntürk; Özdaş, Sibel; Özdaş, Talih; Baştimur, Sibel; Muz, Sami Engin; Öz, Işılay; Kurt, Kenan; İzbirak, Afife; Babademez, Mehmet Ali; Vatandaş, Nilgün

2017-08-01

Adenoid hypertrophy is a condition that presents itself as the chronic enlargement of adenoid tissues; it is frequently observed in the pediatric population. The Ugrp2 gene, a member of the secretoglobin superfamily, encodes a low-molecular weight protein that functions in the differentiation of upper airway epithelial cells. However, little is known about the association of Ugrp2 genetic variations with adenoid hypertrophy. The aim of this study is to investigate the association of single nucleotide polymorphisms in the Ugrp2 gene with adenoid hypertrophy and its related phenotypes. A total of 219 children, comprising 114 patients suffering from adenoid hypertrophy and 105 healthy patients without adenoid hypertrophy, were enrolled in this study. Genotypes of the Ugrp2 gene were determined by DNA sequencing. We identified four single nucleotide polymorphisms (IVS1-189G>A, IVS1-89T>G, c.201delC, and IVS2-15G>A) in the Ugrp2 gene. Our genotype analysis showed that the Ugrp2 (IVS1-89T>G) TG and (c.201delC) CdelC genotypes and their minor alleles were associated with a considerable increase in the risk of adenoid hypertrophy compared with the controls (p=0.012, p=0.009, p=0.013, and p=0.037, respectively). Furthermore, Ugrp2 (GTdelCG, GTdelCA) haplotypes were significantly associated with adenoid hypertrophy (four single nucleotide polymorphisms ordered from 5' to 3'; p=0.0001). Polymorfism-Polymorfism interaction analysis indicated a strong interaction between combined genotypes of the Ugrp2 gene contributing to adenoid hypertrophy, as well as an increased chance of its diagnosis (p<0.0001). In addition, diplotypes carrying the mutant Ugrp2 (c.201delC) allele were strongly associated with an increased risk of adenoid hypertrophy with asthma and adenoid hypertrophy with allergies (p=0.003 and p=0.0007, respectively). Some single nucleotide polymorphisms and their combinations in the Ugrp2 gene are associated with an increased risk of developing adenoid hypertrophy

Extra-Esophageal Pepsin from Stomach Refluxate Promoted Tonsil Hypertrophy.

Directory of Open Access Journals (Sweden)

Jin Hyun Kim

Full Text Available Gastroesophageal reflux is associated with numerous pathologic conditions of the upper aerodigestive tract. Gastric pepsin within reflux contributes to immunologic reactions in the tonsil. In this study, we aimed to find the relationships between pepsin and tonsillar hypertrophy.We explored the notion whether tonsillar hypertrophy was due to pepsin-mediated gastric reflux in tonsil hypertrophy. Fifty-four children with tonsil hypertrophy and 30 adults with tonsillitis were recruited before surgical treatment. Blood and tonsil tissues from each patient were harvested for analysis of changes in lymphocyte and macrophage numbers coupled with histological and biochemical analysis. Pepsin was expressed at different levels in tonsil tissues from each tonsillar hypertrophy. Pepsin-positive cells were found in the crypt epithelium, surrounding the lymphoid follicle with developing fibrosis, and also surrounding the lymphoid follicle that faced the crypt. And also, pepsin staining was well correlated with damaged tonsillar squamous epithelium and TGF-β1 and iNOS expression in the tonsil section. In addition, pepsin and TGF-β1-positive cells were co-localized with CD68-positive cells in the crypt and surrounding germinal centers. In comparison of macrophage responsiveness to pepsin, peripheral blood mononuclear cells (PBMNCs were noticeably larger in the presence of activated pepsin in the child group. Furthermore, CD11c and CD163-positive cells were significantly increased by activated pepsin. However, this was not seen for the culture of PBMNCs from the adult group.The lymphocytes and monocytes are in a highly proliferative state in the tonsillar hypertrophy and associated with increased expression of pro-inflammatory factors as a result of exposure to stomach reflux pepsin.

Melatonin protects against myocardial hypertrophy induced by lipopolysaccharide.

Science.gov (United States)

Lu, Qi; Yi, Xin; Cheng, Xiang; Sun, Xiaohui; Yang, Xiangjun

2015-04-01

Melatonin is thought to have the ability of antiatherogenic, antioxidant, and vasodilatory. It is not only a promising protective in acute myocardial infarction but is also a useful tool in the treatment of pathological remodeling. However, its role in myocardial hypertrophy remains unclear. In this study, we investigated the protective effects of melatonin on myocardial hypertrophy induced by lipopolysaccharide (LPS) and to identify their precise mechanisms. The cultured myocardial cell was divided into six groups: control group, LPS group, LPS + ethanol (4%), LPS + melatonin (1.5 mg/ml) group, LPS + melatonin (3 mg/ml) group, and LPS + melatonin (6 mg/ml) group. The morphologic change of myocardial cell was observed by inverted phase contrast microscope. The protein level of myocardial cell was measured by Coomassie brilliant blue protein kit. The secretion level of tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay (ELISA). Ca(2+) transient in Fura-2/AM-loaded cells was measured by Till image system. The expression of Ca(2+)/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) was measured by Western blot analysis. Our data demonstrated that LPS induced myocardial hypertrophy, promoted the secretion levels of TNF-α, and increased Ca(2+) transient level and the expression of CaMKII and CaN. Administration of melatonin 30 min prior to LPS stimulation dose-dependently attenuated myocardial hypertrophy. In conclusion, the results revealed that melatonin had the potential to protect against myocardial hypertrophy induced by LPS in vitro through downregulation of the TNF-α expression and retains the intracellular Ca(2+) homeostasis.

Painful unilateral temporalis muscle enlargement: reactive masticatory muscle hypertrophy.

Science.gov (United States)

Katsetos, Christos D; Bianchi, Michael A; Jaffery, Fizza; Koutzaki, Sirma; Zarella, Mark; Slater, Robert

2014-06-01

An instance of isolated unilateral temporalis muscle hypertrophy (reactive masticatory muscle hypertrophy with fiber type 1 predominance) confirmed by muscle biopsy with histochemical fiber typing and image analysis in a 62 year-old man is reported. The patient presented with bruxism and a painful swelling of the temple. Absence of asymmetry or other abnormalities of the craniofacial skeleton was confirmed by magnetic resonance imaging and cephalometric analyses. The patient achieved symptomatic improvement only after undergoing botulinum toxin injections. Muscle biopsy is key in the diagnosis of reactive masticatory muscle hypertrophy and its distinction from masticatory muscle myopathy (hypertrophic branchial myopathy) and other non-reactive causes of painful asymmetric temporalis muscle enlargement.

Isolated unilateral temporalis muscle hypertrophy in a child: a case report with literature review.

Science.gov (United States)

Ranasinghe, Jagath C; Wickramasinghe, Chandani; Rodrigo, Ganganath

2018-02-19

Temporalis muscle hypertrophy is a rare entity of masticatory muscle hypertrophy. All types of masticatory muscle hypertrophies have been documented of which temporalis muscle hypertrophy is one. Temporalis muscle hypertrophy is most commonly bilateral and usually associated with other types of masticatory muscles hypertrophy such as masseter or pterygoid hypertrophy. However, isolated unilateral temporalis muscle hypertrophy is extremely rare and only 9 cases have been reported to date in English literature since 1990 with only two patients less than 18 years. There is no exact etiology identified and the diagnosis is made by muscle biopsy combined with imaging study to exclude other possibilities. Age at presentation is ranges from 15 to 65 years with involvement of both sexes. We report the youngest child who is a seven year old girl with right side isolated unilateral temporalis muscle hypertrophy. In this patient, we discuss the youngest child with isolated unilateral temporalis muscle hypertrophy and literature review to date. The patient is a seven year old female presenting with painless swelling of the right temporalis muscle. There had no features of inflammation, trauma, neoplasm or history of parafunctions such as bruxism. The child was not complaining significantly headache or visual disturbances as well. She had undergone radiological assessment with ultrasound scan and contrast MRI. The diagnosis was confirmed by muscle biopsy which shows normal muscle architecture. She was managed conservatively with regular follow up. Isolated unilateral temporalis muscle hypertrophy is extremely rare in children. However this case raises the importance of considering alternative diagnoses despite the condition being rare in the pediatric population.

Lipid droplets hypertrophy: a crucial determining factor in insulin regulation by adipocytes

Science.gov (United States)

Sanjabi, Bahram; Dashty, Monireh; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Rahimi, Mehran; Vinciguerra, Manlio; van Rooij, Felix; Al-Lahham, Saad; Sheedfar, Fareeba; van Kooten, Theo G.; Spek, C. Arnold; Rowshani, Ajda T.; van der Want, Johannes; Klaassen, Rene; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

2015-03-01

Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete insulin, which is biologically functional. Insulin concentrations and release are fat mass- and LDs-dependent respectively. Fat reduction mediated by bariatric surgery repairs obesity-associated T2D. The expression of genes, like PCSK1 (proinsulin conversion enzyme), GCG (Glucagon), GPLD1, CD38 and NNAT, involved in insulin regulation/release were differentially expressed in pancreas and adipose tissue (AT). INS (insulin) and GCG expression reduced in human AT-T2D as compared to AT-control, but remained unchanged in pancreas in either state. Insulin levels (mRNA/protein) were higher in AT derived from prediabetes BB rats with destructed pancreatic β-cells and controls than pancreas derived from the same rats respectively. Insulin expression in 10 human primary cell types including adipocytes and macrophages is an evidence for extrapancreatic insulin-producing cells. The data suggest a crosstalk between AT and pancreas to fine-tune energy metabolic system or may minimize the metabolic damage during diabetes. This study opens new avenues towards T2D therapy with a great impact on public health.

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

Energy Technology Data Exchange (ETDEWEB)

Feng, H.J.; Ouyang, W.; Liu, J.H.; Sun, Y.G.; Hu, R.; Huang, L.H.; Xian, J.L. [Southern Medical University, Department of Nuclear Medicine, Zhujiang Hospital, Guangzhou, China, Department of Nuclear Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Jing, C.F.; Zhou, M.J. [Sun Yat-Sen University, South China Sea Marine Biotechnology, National Engineering Research Center, Guangzhou, China, National Engineering Research Center, South China Sea Marine Biotechnology, Sun Yat-Sen University, Guangzhou (China)

2014-04-11

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs.

Science.gov (United States)

Cai, Chunbo; Qian, Lili; Jiang, Shengwang; Sun, Youde; Wang, Qingqing; Ma, Dezun; Xiao, Gaojun; Li, Biao; Xie, Shanshan; Gao, Ting; Chen, Yaoxing; Liu, Jie; An, Xiaorong; Cui, Wentao; Li, Kui

2017-05-23

Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation (Mstn -/- ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn -/- pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue. Additionally, the serum insulin level decreased and the insulin sensitivity increased significantly in Mstn -/- pigs. Moreover, we found a significant increase in levels of insulin receptor and insulin receptor substrate proteins in skeletal muscle of Mstn -/- pigs, which then activating the insulin signaling pathway. Irisin-mediated regulation is not the only pathway for the activation of insulin signal in Mstn -/- skeletal muscle. This study provides valuable insight for the treatment of human obesity and diabetes mellitus.

Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy

Energy Technology Data Exchange (ETDEWEB)

Chen, Ai-Lan [Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Ou, Cai-Wen [The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); He, Zhao-Chu [Department of Cardiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Liu, Qi-Cai [Experimental Medical Research Center, Guangzhou Medical University, Guangzhou (China); Dong, Qi [Department of Physiology, Guangzhou Medical University, Guangzhou (China); Chen, Min-Sheng [Guangzhou Key Laboratory of Cardiovascular Disease, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China)

2012-10-15

Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [{sup 3}H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.

Dose-response of 1, 3, and 5 sets of resistance exercise on strength, local muscular endurance, and hypertrophy.

Science.gov (United States)

Radaelli, Regis; Fleck, Steven J; Leite, Thalita; Leite, Richard D; Pinto, Ronei S; Fernandes, Liliam; Simão, Roberto

2015-05-01

The study's purpose was to compare the response of performing 1, 3, and 5 sets on measures of performance and muscle hypertrophy. Forty-eight men, with no weight training experience, were randomly assigned to one of the 3 training groups, 1 SET, 3 SETS, 5 SETS, or control group. All training groups performed 3 resistance training sessions per week for 6 months. The 5 repetition maximum (RM) for all training groups increased in the bench press (BP), front lat pull down (LPD), shoulder press (SP), and leg press (LP) (p ≤ 0.05), with the 5 RM increases in the BP and LPD being significantly greater for 5 SETS compared with the other training groups (p ≤ 0.05). Bench press 20 RM in the 3-SET and 5-SET groups significantly increased with the increase being significantly greater than the 1-SET group and the 5-SET group increase being significantly greater than the 3-SET group (p ≤ 0.05). LP 20 RM increased in all training groups (p ≤ 0.05), with the 5-SETS group showing a significantly greater increase than the 1-SET group (p ≤ 0.05). The 3-SET and 5-SET groups significantly increased elbow flexor muscle thickness (MT) with the 5-SET increase being significantly greater than the other 2 training groups (p ≤ 0.05). The 5-SET group significantly increased elbow extensor MT with the increase being significantly greater than the other training groups (p ≤ 0.05). All training groups decreased percent body fat, increased fat-free mass, and vertical jump ability (p ≤ 0.05), with no differences between groups. The results demonstrate a dose-response for the number of sets per exercise and a superiority of multiple sets compared with a single set per exercise for strength gains, muscle endurance, and upper arm muscle hypertrophy.

Myocardial hypertrophy in the recipient with twin-to-twin transfusion syndrome

DEFF Research Database (Denmark)

Jeppesen, D.L.; Jorgensen, F.S.; Pryds, O.A.

2008-01-01

pressure measurements revealed persistent systemic hypertension. Biventricular hypertrophy was demonstrated by echocardiography. Blood pressure normalised after treatment with Nifedipine and the cardiac hypertrophy subsided over the following weeks. A potential contributing mechanism is intrauterine...

19-Hydroxyeicosatetraenoic acid and isoniazid protect against angiotensin II-induced cardiac hypertrophy

Energy Technology Data Exchange (ETDEWEB)

Elkhatali, Samya; El-Sherbeni, Ahmed A.; Elshenawy, Osama H. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Abdelhamid, Ghada [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Helwan (Egypt); El-Kadi, Ayman O.S., E-mail: aelkadi@ualberta.ca [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada)

2015-12-15

We have recently demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE formed in the heart tissue, and its formation was decreased during cardiac hypertrophy. In the current study, we examined whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy. The effect of Ang II, with and without 19-HETE (20 μM), on the development of cellular hypertrophy in cardiomyocyte RL-14 cells was assessed by real-time PCR. Also, cardiac hypertrophy was induced in Sprague–Dawley rats by Ang II, and the effect of increasing 19-HETE by isoniazid (INH; 200 mg/kg/day) was assessed by heart weight and echocardiography. Also, alterations in cardiac cytochrome P450 (CYP) and their associated arachidonic acid (AA) metabolites were determined by real-time PCR, Western blotting and liquid-chromatography–mass-spectrometry. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy in vitro, as indicated by the significant reduction in β/α-myosin heavy chain ratio. In vivo, INH improved heart dimensions, and reversed the increase in heart weight to tibia length ratio caused by Ang II. We found a significant increase in cardiac 19-HETE, as well as a significant reduction in AA and its metabolite, 20-HETE. In conclusion, 19-HETE, incubated with cardiomyocytes in vitro or induced in the heart by INH in vivo, provides cardioprotection against Ang II-induced hypertrophy. This further confirms the role of CYP, and their associated AA metabolites in the development of cardiac hypertrophy. - Highlights: • We found 19-hydroxy arachidonic acid to protect cardiomyocytes from hypertrophy. • We validated the use of isoniazid as a cardiac 19-hydroxy arachidonic acid inducer. • We found isoniazid to increase protective and inhibit toxic eicosanoides. • We found isoniazid to protect against angiotensin-induced cardiac hypertrophy. • This will help to

Health-related quality of life among children with adenoid hypertrophy in Xi'an, China.

Science.gov (United States)

Jiang, Xun; Ren, Xiaoyong; Liu, Haiqin; Tian, Jiao; Du, Chunyan; Luo, Huanan; Cheng, Ying; Shang, Lei

2015-12-01

The aim of this study was to investigate the health-related quality of life (HRQOL) in 5-7-year-old children diagnosed with adenoid hypertrophy and the impact of adenoid hypertrophy on affected families. This is a cross-sectional case-control study evaluating 5-7-year-old children with adenoid hypertrophy (n=195), 5-7-year-old healthy children (n=156), and associated caregivers (parents and/or grandparents). A Chinese version of the PedsQL™ 4.0 Generic Core Scale was used to assess childhood HRQOL, and a Chinese version of the Family Impact Module (FIM) was used to assess the impact of adenoid hypertrophy on family members. HRQOL scores were compared between the children with adenoid hypertrophy and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, and caregiver's HRQOL as independent variables were referenced to determine the factors that may influence HRQOL in children with adenoid hypertrophy. Children with adenoid hypertrophy showed significantly lower physical, emotional, social, and school functioning scores than healthy children (pchildren with adenoid hypertrophy also scored significantly lower than caregivers for healthy children on physical, emotional, social, cognitive, and communication functioning (pchildren also exhibited significantly higher levels of worry than healthy children (pchildren's age, children's relation with caregivers, caregiver's educational level, caregiver's own HRQOL, and the size of adenoid may all influence the HRQOL in children with adenoid hypertrophy (pchildren and their caregivers, and may negatively influence family functioning. In addition, caregivers' social characteristics may also significantly affect the HRQOL in children with adenoid hypertrophy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Satellite cell depletion prevents fiber hypertrophy in skeletal muscle.

Science.gov (United States)

Egner, Ingrid M; Bruusgaard, Jo C; Gundersen, Kristian

2016-08-15

The largest mammalian cells are the muscle fibers, and they have multiple nuclei to support their large cytoplasmic volumes. During hypertrophic growth, new myonuclei are recruited from satellite stem cells into the fiber syncytia, but it was recently suggested that such recruitment is not obligatory: overload hypertrophy after synergist ablation of the plantaris muscle appeared normal in transgenic mice in which most of the satellite cells were abolished. When we essentially repeated these experiments analyzing the muscles by immunohistochemistry and in vivo and ex vivo imaging, we found that overload hypertrophy was prevented in the satellite cell-deficient mice, in both the plantaris and the extensor digitorum longus muscles. We attribute the previous findings to a reliance on muscle mass as a proxy for fiber hypertrophy, and to the inclusion of a significant number of regenerating fibers in the analysis. We discuss that there is currently no model in which functional, sustainable hypertrophy has been unequivocally demonstrated in the absence of satellite cells; an exception is re-growth, which can occur using previously recruited myonuclei without addition of new myonuclei. © 2016. Published by The Company of Biologists Ltd.

Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

Directory of Open Access Journals (Sweden)

Ping-Chun Li

2012-01-01

Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

Effect of strength training on regional hypertrophy of the elbow flexor muscles.

Science.gov (United States)

Drummond, Marcos D M; Szmuchrowski, Leszek A; Goulart, Karine N O; Couto, Bruno P

2016-10-01

Muscle hypertrophy is the main structural adaptation to strength training. We investigated the chronic effects of strength training on muscle hypertrophy in different regions of the elbow flexor muscles. Eleven untrained men (21.8 ± 1.62 years) underwent magnetic resonance imaging to determine the proximal, medial, distal, and mean cross-sectional areas (CSA) of the elbow flexors. The volunteers completed 12 weeks of strength training. The training protocol consisted of 4 sets of 8-10 maximum repetitions of unilateral elbow flexion. The interval between sets was 120 s. The training frequency was 3 sessions per week. The magnetic resonance images verified the presence of significant and similar hypertrophy in the distal, medial, and proximal portions of the elbow flexor muscles. Muscle hypertrophy may be assessed using only the medial CSA. We should not expect different degrees of hypertrophy among the regions of the elbow flexor muscles. Muscle Nerve 54: 750-755, 2016. © 2016 Wiley Periodicals, Inc.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

Energy Technology Data Exchange (ETDEWEB)

Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo, E-mail: pompeo.volpe@unipd.it

2013-07-15

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

International Nuclear Information System (INIS)

Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo

2013-01-01

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α 1 -adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

Science.gov (United States)

McCarthy, John J.; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B.; Srikuea, Ratchakrit; Lawson, Benjamin A.; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S.; Esser, Karyn A.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.

2011-01-01

An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells. PMID:21828094

MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone.

Science.gov (United States)

Diniz, Gabriela Placoná; Lino, Caroline Antunes; Moreno, Camila Rodrigues; Senger, Nathalia; Barreto-Chaves, Maria Luiza Morais

2017-12-01

It is well-known that increased thyroid hormone (TH) levels induce cardiomyocyte growth. MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with increased risk of heart failure. In this study, we evaluated the miR-1 expression in TH-induced cardiac hypertrophy, as well as the potential involvement of miR-1 in cardiomyocyte hypertrophy elicited by TH in vitro. The possible role of type 1 angiotensin II receptor (AT1R) in the effect promoted by TH in miR-1 expression was also evaluated. Neonatal rat cardiac myocytes (NRCMs) were treated with T 3 for 24 hr and Wistar rats were subjected to hyperthyroidism for 14 days combined or not with AT1R blocker. Real Time RT-PCR analysis indicated that miR-1 expression was decreased in cardiac hypertrophy in response to TH in vitro and in vivo, and this effect was unchanged by AT1R blocker. In addition, HDAC4, which is target of miR-1, was increased in NRCMs after T 3 treatment. A gain-of-function study revealed that overexpression of miR-1 prevented T 3 -induced cardiomyocyte hypertrophy and reduced HADC4 mRNA levels in NRCMs. In vivo experiments confirmed the downregulation of miR-1 in cardiac tissue from hyperthyroid animals, which was accompanied by increased HDAC4 mRNA levels. In addition, HDAC inhibitor prevented T 3 -induced cardiomyocyte hypertrophy. Our data reveal a new mechanistic insight into cardiomyocyte growth in response to TH, suggesting that miR-1 plays a role in cardiomyocyte hypertrophy induced by TH potentially via targeting HADC4. © 2017 Wiley Periodicals, Inc.

Left ventricular hypertrophy in children, adolescents and young adults with sickle cell anemia

Directory of Open Access Journals (Sweden)

Gustavo Baptista de Almeida Faro

2015-10-01

Full Text Available OBJECTIVE: The aims of this study were to estimate the frequency of left ventricular hypertrophy and to identify variables associated with this condition in under 25-year-old patients with sickle cell anemia.METHODS: A cross-sectional study was performed of children, adolescents and young adults with sickle cell anemia submitted to a transthoracic Doppler echocardiography. The mass of the left ventricle was determined by the formula of Devereux et al. with correction for height, and the percentile curves of gender and age were applied. Individuals with rheumatic and congenital heart disease were excluded. The patients were divided into two groups according to the presence or absence of left ventricular hypertrophy and compared according to clinical, echocardiographic and laboratory variables.RESULTS: A total of 37.6% of the patients had left ventricular hypertrophy in this sample. There was no difference between the groups of patients with and without hypertrophy according to pathological history or clinical characteristics, except possibly for the use of hydroxyurea, more often used in the group without left ventricular hypertrophy. Patients with left ventricular hypertrophy presented larger left atria and lower hemoglobin and hematocrit levels, reticulocyte index and a higher albumin:creatinine ratio in urine.CONCLUSION: Left ventricular hypertrophy was observed in more than one-third of the young patients with sickle cell anemia with this finding being inversely correlated to the hemoglobin and hematocrit levels, and reticulocyte index and directly associated to a higher albumin/creatinine ratio. It is possible that hydroxyurea had had a protective effect on the development of left ventricular hypertrophy.

Thin-plate spline analysis of craniofacial morphology in subjects with adenoid or tonsillar hypertrophy.

Science.gov (United States)

Baroni, Michela; Ballanti, Fabiana; Polimeni, Antonella; Franchi, Lorenzo; Cozza, Paola

2011-04-01

To compare the skeletal features of subjects with adenoid hypertrophy with those of children with tonsillar hypertrophy using thin-plate spline (TPS) analysis. A group of 20 subjects (9 girls and 11 boys; mean age 8.4 ± 0.9 years) with adenoid hypertrophy (AG) was compared with a group of 20 subjects (10 girls and 10 boys; mean age 8.2 ± 1.1 years) with tonsillar hypertrophy (TG). Craniofacial morphology was analyzed on the lateral cephalograms of the subjects in both groups by means of TPS analysis. A cross-sectional comparison was performed on both size and shape differences between the two groups. AG exhibited statistically significant shape and size differences in craniofacial configuration with respect to TG. Subjects with adenoid hypertrophy showed an upward dislocation of the anterior region of the maxilla, a more downward/backward position of the anterior region of the mandibular body and an upward/backward displacement of the condylar region. Conversely, subjects with tonsillar hypertrophy showed a downward dislocation of the anterior region of the maxilla, a more upward/forward position of the anterior region of the mandibular body and a downward/forward displacement of the condylar region. Subjects with adenoid hypertrophy exhibited features suggesting a more retrognathic mandible while subjects with tonsillar hypertrophy showed features suggesting a more prognathic mandible. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Operative intercostal chest drain is not required following extrapleural or transpleural esophageal atresia repair.

Science.gov (United States)

Paramalingam, Saravanakumar; Burge, David M; Stanton, Michael P

2013-08-01

Approximately half of the United Kingdom patients undergoing esophageal atresia (OA) repair have an operative intercostal chest drain (ICD) placed (2008 British Association of Pediatric Surgeons Congenital Anomalies Surveillance Study data). We reviewed our experience of OA repairs to evaluate if an ICD placement is necessary. Patients with OA/distal tracheoesophageal fistula (TOF), treated between January 1990 and January 2010, were identified by retrospective review of a prospectively maintained electronic database and patient case notes. A total of 112 consecutive patients were identified, of whom 107 were included (73 male). Five were excluded as no case notes were available. Median birth weight was 2,597 g (range 924 to 4,245 g) and median gestational age was 38 weeks (27 to 41 weeks). Median age at discharge was 22 days (3 to 440 days) and median follow-up was 3.5 years (0 to 18 years). Patients were analyzed in two groups-group 1 (n = 73) had an extrapleural (EP) repair, of which 23 had a pleural breach and group 2 (n = 34) had a purposeful transpleural (TP) approach (surgeon preference). Eleven patients (10%) had an operative ICD, of which six patients were in group 1 and five in group 2. These 11 patients had an uncomplicated postoperative course and all operative ICD were removed within 48 hours of surgery. Of the 96 patients that did not have an operative ICD, only 2 (2%) required postoperative intervention. One patient, in group 2, had a postoperative ICD inserted for a simple pneumothorax at 12 hours and removed at 48 hours. The other patient, in group 1, had a clinically detected anastomotic leak after 48 hours and required operative repair. An operative ICD is not required following OA/distal TOF repair, whether the approach is EP or TP. ICD that were electively placed (in 10%) served no clinical purpose. Georg Thieme Verlag KG Stuttgart · New York.

[Obstructive sleep apnea-hypopnea syndrome in children: beyond adenotonsillar hypertrophy].

Science.gov (United States)

Esteller, Eduard

2015-01-01

The prevalence of obstructive sleep apnea-hypopnea syndrome in the general childhood population is 1-2% and the most common cause is adenotonsillar hypertrophy. However, beyond adenotonsillar hypertrophy, there are other highly prevalent causes of this syndrome in children. The causes are often multifactorial and include muscular hypotonia, dentofacial abnormalities, soft tissue hypertrophy of the airway, and neurological disorders). Collaboration between different specialties involved in the care of these children is essential, given the wide variability of conditions and how frequently different factors are involved in their genesis, as well as the different treatments to be applied. We carried out a wide literature review of other causes of obstructive sleep apnea-hypopnea syndrome in children, beyond adenotonsillar hypertrophy. We organised the prevalence of this syndrome in each pathology and the reasons that cause it, as well as their interactions and management, in a consistent manner. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

The metabolic and temporal basis of muscle hypertrophy in response to resistance exercise.

Science.gov (United States)

Brook, Matthew S; Wilkinson, Daniel J; Smith, Kenneth; Atherton, Philip J

2016-09-01

Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great importance for maintaining health and quality-of-life into older age, under conditions of cachectic disease and with rehabilitation. In healthy weight-bearing individuals, muscle mass is maintained by the equilibrium between muscle protein synthesis (MPS) and muscle protein breakdown; when this balance tips in favour of MPS hypertrophy occurs. Despite considerable research into pharmacological/nutraceutical interventions, resistance exercise training (RE-T) remains the most potent stimulator of MPS and hypertrophy (in the majority of individuals). However, the mechanism(s) and time course of hypertrophic responses to RE-T remain poorly understood. We would suggest that available data are very much in favour of the notion that the majority of hypertrophy occurs in the early phases of RE-T (though still controversial to some) and that, for the most part, continued gains are hard to come by. Whilst the mechanisms of muscle hypertrophy represent the culmination of mechanical, auto/paracrine and endocrine events, the measurement of MPS remains a cornerstone for understanding the control of hypertrophy - mainly because it is the underlying driving force behind skeletal muscle hypertrophy. Development of sophisticated isotopic techniques (i.e. deuterium oxide) that lend to longer term insight into the control of hypertrophy by sustained RE-T will be paramount in providing insights into the metabolic and temporal regulation of hypertrophy. Such technologies will have broad application in muscle mass intervention for both athletes and for mitigating disease/age-related cachexia and sarcopenia, alike.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

Science.gov (United States)

Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert T; Liu, Xuhui

2014-01-01

extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

Science.gov (United States)

Fernandes, T; Soci, U P R; Oliveira, E M

2011-09-01

Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

Directory of Open Access Journals (Sweden)

T. Fernandes

2011-09-01

Full Text Available Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1 receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

International Nuclear Information System (INIS)

Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Zhou, Heng; Xu, Dachun; Shan, Tichao; Zhang, Fan; Guo, Yuan; Chen, Yuguo; Wu, Dawei

2015-01-01

Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

Energy Technology Data Exchange (ETDEWEB)

Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

2015-09-01

Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy.

Science.gov (United States)

Goh, Qingnian; Millay, Douglas P

2017-02-10

Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy. This blunted hypertrophic response was associated with a reduction in Akt and p70s6k signaling and protein synthesis, suggesting a link between myonuclear accretion and activation of pro-hypertrophic pathways. Furthermore, fusion-incompetent muscle exhibited increased fibrosis after muscle overload, indicating a protective role for normal stem cell activity in reducing myofiber strain associated with hypertrophy. These findings reveal an essential contribution of myomaker-mediated stem cell fusion during physiological adult muscle hypertrophy.

Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats via adenosine monophosphate (AMP)-activated protein kinase activation and inhibition of lipogenesis-associated genes.

Science.gov (United States)

Chiu, Chen-Yuan; Chan, Im-Lam; Yang, Tsung-Han; Liu, Shing-Hwa; Chiang, Meng-Tsan

2015-03-25

This study investigated the role of chitosan in lipogenesis in high-fat diet-induced obese rats. The lipogenesis-associated genes and their upstream regulatory proteins were explored. Diet supplementation of chitosan efficiently decreased the increased weights in body, livers, and adipose tissues in high-fat diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate; attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein lipase activity in epididymal adipose tissues; and decreased hepatic enzyme activities of lipid biosynthesis. Chitosan supplementation significantly activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and attenuated high-fat diet-induced protein expressions of lipogenic transcription factors (PPAR-γ and SREBP1c) in livers and adipose tissues. Moreover, chitosan supplementation significantly inhibited the expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in livers and adipose tissues of high-fat diet-fed rats. These results demonstrate for the first time that chitosan supplementation alleviates high-fat diet-enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene inhibition.

Doege-Potter syndrome presenting with hypoinsulinemic hypoglycemia in a patient with a malignant extrapleural solitary fibrous tumor: a case report

Directory of Open Access Journals (Sweden)

Schutt Robert C

2013-01-01

Full Text Available Abstract Introduction Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. This tumor causes hypoglycemia by the secretion of a prohormone form of insulin-like growth factor II. We describe the diagnosis and management of Doege-Potter syndrome and the use of transarterial chemoembolization in a patient with a malignant extrapleural solitary fibrous tumor. Case presentation Our patient was a 64-year-old Caucasian woman who initially presented with urinary incontinence and was found to have a 14.5×9.0×9.0cm retroperitoneal solitary fibrous tumor compressing her bladder. Her tumor was surgically resected but recurred with multiple hepatic metastatic lesions. The hepatic metastases progressed despite systemic chemotherapy and treatment with doxorubicin transarterial chemoembolization. Her course was complicated by the development of recurrent fasting hypoglycemia, most likely secondary to Doege-Potter syndrome. Her hypoglycemia was managed with corticosteroid therapy and frequent scheduled nutrient intake overnight. Conclusions The rarity of hepatic solitary fibrous tumors and consequent lack of controlled trials make this report significant in that it describes the diagnostic approach to Doege-Potter syndrome, describes our experience with the use of doxorubicin transarterial chemoembolization, and presents management options for tumor-associated hypoglycemia in the case of extensive disease not amenable to surgical resection.

Myocardial uptake of thallium-201 in rat with cardiac hypertrophy

International Nuclear Information System (INIS)

Torii, Yukio; Adachi, Haruhiko; Kizu, Akira; Nakagawa, Masao; Ijichi, Hamao

1985-01-01

The thallium-201 (TL) has been used in order to diagnose myocardial infarction and ischemia. Although it is well known that TL distributes in the myocardium in proportion to the distribution of coronary blood flow, the biological property of TL in the loaded myocardium remains unclear. We studied the myocardial uptake of TL in rat with cardiac hypertrophy. Experiments were performed in 30 anesthetized rats devided into 3 groups; control group (C,N=14), hypertrophy group (H,N=6) and diltiazem group (D, 0.3 mg/kg/min. IV. N=10). Cardiac hypertrophy was produced with the banding of the ascending aorta. Myocardial blood flow (MBF) was measured by microspheres labeled with Strontium-85. Cardiac weight was increased in H, and both MBF and TL uptake were proportionally increased. MBF was negatively correlated with the extraction fraction in C (r=-0.71), in H (r=-0.66) and in D (r=-0.85), and this relationship in H was significantly different from it in C (p<0.05), but not in D. From these results, we concluded that TL uptake in H is not always dependant on MBF and affected by the altered metabolism of hypertrophied myocardium. (author)

[Impacts of physical exercise on remodeling and hypertrophy of skeletal muscle.

Science.gov (United States)

Sakashita, Yoshihiro; Uchida, Takayuki; Nikawa, Takeshi

The skeletal muscle has high sensitivity for the mechanical stress. Because it is enlarged by training, whereas it is easily withered by lack of exercise. When we exercise, skeletal muscle cells per se sense mechanical loading, and muscular remodeling and the muscular hypertrophy occur. It has been revealed that the intracellular signaling through PGC-1α participates in the remodeling of the skeletal muscle, while PGC-1α4, an isoform of PGC-1α, and the dystrophin-glycoprotein complex play important roles in muscular hypertrophy. This review describes the impact of physical exercise gives on the remodeling and hypertrophy of muscle through the signaling.

Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

Directory of Open Access Journals (Sweden)

Leonidas Apostolidis

Full Text Available To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP by magnetic resonance neurography (MRN.Twenty patients (7 female, 13 male, 58.9±10.0 years with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG, sciatic nerve normalized T2 (nT2 signal and caliber, and fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD. Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001 was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80 and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16. AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

OpenAIRE

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, ...

High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice.

Science.gov (United States)

Tsuduki, Tsuyoshi; Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu

2015-07-17

This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.

Isolated papillary muscle hypertrophy: A gap in our knowledge of hypertrophic cardiomyopathy?

Science.gov (United States)

Ferreira, Catarina; Delgado, Carlos; Vázquez, María; Trinidad, Carmen; Vilar, Manuel

2014-06-01

Increased thickness of left ventricular walls is the predominant characteristic and one of the diagnostic criteria of hypertrophic cardiomyopathy (HCM). This case illustrates an uncommon but important finding of isolated hypertrophy of the papillary muscles (PMs), observed in a young woman in whom an abnormal electrocardiogram was initially detected. During the investigation isolated PM hypertrophy was identified. The structural characteristics of the PMs have received scant attention in this setting and there is little information in the literature on this entity, whose real prevalence and clinical significance remain to be determined. The available information relates solitary PM hypertrophy with an early form or a different pattern of HCM. In this case PM hypertrophy was only detected due to the finding of an abnormal electrocardiogram, which prompted further diagnostic tests and a search for possible etiologies. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Transcription Factors in Heart: Promising Therapeutic Targets in Cardiac Hypertrophy

OpenAIRE

Kohli, Shrey; Ahuja, Suchit; Rani, Vibha

2011-01-01

Regulation of gene expression is central to cell growth, differentiation and diseases. Context specific and signal dependent regulation of gene expression is achieved to a large part by transcription factors. Cardiac transcription factors regulate heart development and are also involved in stress regulation of the adult heart, which may lead to cardiac hypertrophy. Hypertrophy of cardiac myocytes is an outcome of the imbalance between prohypertrophic factors and anti-hypertrophic factors. Thi...

High-intensity interval training has beneficial effects on cardiac remodeling through local renin-angiotensin system modulation in mice fed high-fat or high-fructose diets.

Science.gov (United States)

de Oliveira Sá, Guilherme; Dos Santos Neves, Vívian; de Oliveira Fraga, Shyrlei R; Souza-Mello, Vanessa; Barbosa-da-Silva, Sandra

2017-11-15

HIIT (high-intensity interval training) has the potential to reduce cardiometabolic risk factors, but the effects on cardiac remodeling and local RAS (renin-angiotensin system) in mice fed high-fat or high-fructose diets still need to be fully addressed. Sixty male C57BL/6 mice (12weeks old) were randomly divided into three groups, control (C), High-fat (HF), or High-fructose diet (HRU) and were monitored for eight weeks before being submitted to the HIIT. Each group was randomly assigned to 2 subgroups, one subgroup was started on a 12-week HIIT protocol (T=trained group), while the other subgroup remained non-exercised (NT=not-trained group). HIIT reduced BM and systolic blood pressure in high-fat groups, while enhanced insulin sensitivity after high-fat or high-fructose intake. Moreover, HIIT reduced left ventricular hypertrophy in HF-T and HFRU-T. Notably, HIIT modulated key factors in the local left ventricular renin-angiotensin-system (RAS): reduced protein expression of renin, ACE (Angiotensin-converting enzyme), and (Angiotensin type 2 receptor) AT2R in HF-T and HFRU-T groups but reduced (Angiotensin type 1 receptor) AT1R protein expression only in the high-fat trained group. HIIT modulated ACE2/Ang (1-7)/Mas receptor axis. ACE2 mRNA gene expression was enhanced in HF-T and HFRU-T groups, complying with elevated Mas (Mas proto-oncogene, G protein-coupled receptor) receptor mRNA gene expression after HIIT. This study shows the effectiveness of HIIT sessions in producing improvements in insulin sensitivity and mitigating LV hypertrophy, though hypertension was controlled only in the high-fat-fed submitted to HIIT protocol. Local RAS system in the heart mediates these findings and receptor MAS seems to play a pivotal role when it comes to the amelioration of cardiac structural and functional remodeling due to HIIT. Copyright © 2017 Elsevier Inc. All rights reserved.

Limited Relationship of Voltage Criteria for Electrocardiogram Left Ventricular Hypertrophy to Cardiovascular Mortality.

Science.gov (United States)

Ha, Le Dung; Elbadawi, Ayman; Froelicher, Victor F

2018-01-01

Numerous methods have been proposed for diagnosing left ventricular hypertrophy using the electrocardiogram. They have limited sensitivity for recognizing pathological hypertrophy, at least in part due to their inability to distinguish pathological from physiological hypertrophy. Our objective is to compare the major electrocardiogram-left ventricular hypertrophy criteria using cardiovascular mortality as a surrogate for pathological hypertrophy. This study was a retrospective analysis of 16,253 veterans electrocardiogram-left ventricular hypertrophy, and there were 744 cardiovascular deaths (annual cardiovascular mortality 0.25%). Receiver operating characteristic analysis demonstrated that the greatest area under the curve (AUC) for classification of cardiovascular death was obtained using the Romhilt-Estes score (0.63; 95% confidence interval, 0.61-0.65). Most of the voltage-only criteria had nondiagnostic area under the curves, with the Cornell being the best at 0.59 (95% confidence interval, 0.57-0.62). When the components of the Romhilt-Estes score were examined using step-wise Wald analysis, the voltage criteria dropped from the model. The Romhilt-Estes score ≥ 4, the Cornell, and the Peguero had the highest association with cardiovascular mortality (adjusted hazard ratios 2.2, 2.0, and 2.1, consecutively). None of the electrocardiogram leads with voltage criteria exhibited sufficient classification power for clinical use. Copyright © 2018 Elsevier Inc. All rights reserved.

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

Science.gov (United States)

Kusaka, Hiroaki; Koibuchi, Nobutaka; Hasegawa, Yu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2016-11-11

The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity.

Science.gov (United States)

Leifheit-Nestler, Maren; Wagner, Nana-Maria; Gogiraju, Rajinikanth; Didié, Michael; Konstantinides, Stavros; Hasenfuss, Gerd; Schäfer, Katrin

2013-07-11

The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels. The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepRdb/db) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepRS1138) were also analyzed. Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepRS1138 animals. LepRS1138 mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepRdb/db and LepRS1138 mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis. Our findings suggest that hearts from obese mice

Congenital hypertrophy of multiple intrinsic muscles of the foot.

Science.gov (United States)

Shiraishi, Tomohiro; Park, Susam; Niu, Atushi; Hasegawa, Hiromi

2014-12-01

Congenital hypertrophy of a single intrinsic muscle of the foot is rare, and as far as we know, only six cases have been reported. We describe a case of congenital anomaly that showed hypertrophy of multiple intrinsic muscles of the foot; the affected muscles were all the intrinsic muscles of the foot except the extensor digitorum brevis or extensor hallucis. Other tissues such as adipose tissue, nervous tissue, or osseous tissue showed no abnormalities. To reduce the volume of the foot we removed parts of the enlarged muscles.

Alterations in NO/ROS ratio and expression of Trx1 and Prdx2 in isoproterenol-induced cardiac hypertrophy

Institute of Scientific and Technical Information of China (English)

Hao Su; Marco Pistolozzi; Xingjuan Shi; Xiaoou Sun; Wen Tan

2017-01-01

The development of cardiac hypertrophy is a complicated process,which undergoes a transition from compensatory hypertrophy to heart failure,and the identification of new biomarkers and targets for this disease is greatly needed.Here we investigated the development of isoproterenol (ISO)-induced cardiac hypertrophy in an in vitro experimental model.After the induction of hypertrophy with ISO treatment in H9c2 cells,cell surface area,cell viability,cellular reactive oxygen species (ROS),and nitric oxide (NO) levels were tested.Our data showed that the cell viability,mitochondrial membrane potential,and NO/ROS balance varied during the development of cardiac hypertrophy in H9c2 cells.It was also found that the expression of thioredoxin1 (Trx1) and peroxiredoxin2 (Prdx2) was decreased during the cardiac hypertrophy of H9c2 cells.These results suggest a critical role for Trx1 and Prdx2 in the cardiac hypertrophy of H9c2 cells and in the transition from compensated hypertrophy to de-compensated hypertrophy in H9c2 cells,and our findings may have important implications for the management of this disease.

[A girl with congenital hemifacial hypertrophy

NARCIS (Netherlands)

Broeke, S.M. van den; Wolvius, E.B.; Adrichem, L.N. van; Baat, C. de

2006-01-01

A girl with congenital hemifacial hypertrophy had been observed and treated by a multidisciplinary team for craniofacial disorders in an academic medical centre since birth. At the age of 8 she was treated on account of considerable facial asymmetry and multiple intraoral problems. The two-step

Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

Science.gov (United States)

Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

2017-03-01

Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF o ), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

Oral insulin improves metabolic parameters in high fat diet fed rats

Directory of Open Access Journals (Sweden)

LEANDRO C. LIPINSKI

2017-08-01

Full Text Available ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL standard chow group; high fat diet low carbohydrates group (HFD and HFD plus daily oral 20U insulin gavage (HFD+INS. Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001, fasting glucose and triglycerides serum levels (p<0,05 an increased intestinal weight of distal ileum (P<0,05. Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05 in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.

The effect of inter-set rest intervals on resistance exercise-induced muscle hypertrophy.

Science.gov (United States)

Henselmans, Menno; Schoenfeld, Brad J

2014-12-01

Due to a scarcity of longitudinal trials directly measuring changes in muscle girth, previous recommendations for inter-set rest intervals in resistance training programs designed to stimulate muscular hypertrophy were primarily based on the post-exercise endocrinological response and other mechanisms theoretically related to muscle growth. New research regarding the effects of inter-set rest interval manipulation on resistance training-induced muscular hypertrophy is reviewed here to evaluate current practices and provide directions for future research. Of the studies measuring long-term muscle hypertrophy in groups employing different rest intervals, none have found superior muscle growth in the shorter compared with the longer rest interval group and one study has found the opposite. Rest intervals less than 1 minute can result in acute increases in serum growth hormone levels and these rest intervals also decrease the serum testosterone to cortisol ratio. Long-term adaptations may abate the post-exercise endocrinological response and the relationship between the transient change in hormonal production and chronic muscular hypertrophy is highly contentious and appears to be weak. The relationship between the rest interval-mediated effect on immune system response, muscle damage, metabolic stress, or energy production capacity and muscle hypertrophy is still ambiguous and largely theoretical. In conclusion, the literature does not support the hypothesis that training for muscle hypertrophy requires shorter rest intervals than training for strength development or that predetermined rest intervals are preferable to auto-regulated rest periods in this regard.

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

Science.gov (United States)

Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

2015-03-18

Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright �

Tissue characteristics in left ventricular hypertrophy using magnetic resonance imaging

International Nuclear Information System (INIS)

Yoshida, Shigeru; Ueno, Yuji; Arita, Mikio; Nishio, Ichiro; Masuyama, Yoshiaki

1988-01-01

For 15 normotensive patients with asymmetric septal hypertrophy (ASH), 10 hypertensive patients with concentric hypertrophy (CH), and five normal subjects (N), we examined changes in myocardial T 1 and T 2 values related to the cardiac cycle. The usefulness of those values in differentiating diseases with left ventricular hypertrophy was evaluated. Left ventricular (LV) short-axis spin echo images and inversion recovery images were obtained at endsystolic and diastolic cardiac phases, and T 1 and T 2 images were calculated. The regional wall thickness (WT) and T 1 and T 2 values were measured in the anterior septum, anterior wall, lateral wall, posterior wall and posterior septum. Myocardial T 1 and T 2 values were significantly decreased in systole (T 1 : 185.6±37.9 msec, T 2 : 24.4±6.3 msec, mean±SD) compared to those in diastole (T 1 : 249.2±56.7 msec, T 2 : 31.7±9.4 msec). In both the ASH and CH groups, significant correlations were observed between diastolic T 1 values and WT (ASH: r = 0.80, p 2 values and WT (ASH: r = 0.58, p 1 values in the ASH group (343.4±40.5 msec) were significantly higher than those of the CH group (247.3±21.4 msec), although the mean wall thickness values were similar in both groups. The T 1 /WT and T 2 /WT were significantly lower in the CH group than those in the ASH and N groups. In conclusion, myocardial T 1 and T 2 values were related not only to the cardiac cycle, but to wall thickness and to types of hypertrophy. The T 1 and T 2 values may be useful for distinguishing hypertrophic cardiomyopathy from hypertrophy due to hypertension. (author)

Association of myocardial cell necrosis with experimental cardiac hypertrophy

Energy Technology Data Exchange (ETDEWEB)

Revis, N W; Cameron, A J.V.

1979-01-01

Cardiac hypertrophy was induced in rabbits by injecting thyroxime or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

Experimental and clinical study of cardiac hypertrophy by thallium-201 myocardial scintigraphy

International Nuclear Information System (INIS)

Torii, Yukio

1983-01-01

I studied experimentally the myocardial uptake of 201 Tl in cardiac hypertrophy in rat, and clinically evaluated cardiac shape and dimension in the patients with various types of cardiac hypertrophy. Experimentally, both myocardial blood flow (MBF) and Tl uptake were increased with cardiac weight. There were negative correlations between the extraction fraction and MBF. Tl uptake in Hypertrophy is not always dependent on MBF and affected by the altered metabolism of hypertrophied myocardium. Clinical study was performed in 29 normal subjects and in 90 patients with heart disease. The measurements of left ventricular (LV) size by Tl scintigraphy were well correlated with them by echocardiography. Aortic stenosis and hypertensive heart disease showed thick wall and spherical shape. Both mitral (MR) and aortic (AR) regurgitation showed ventricular dilatation, spherical shape (in chronic MR) and ellipsoid shape (in acute MR and in AR). Decreased ventricular size but normal shape was observed in mitral stenosis and cor pulmonale. Hypertrophic cardiomyopathy showed thick wall with asymmetric septal hypertrophy, while congestive cardiomyopathy showed thin wall with marked ventricular dilatation and spherical shape. I conclude that heart disease has characteristic figures in dimension and shape which may be reflecting cardiac performance or compensating for the load to the heart, and that 201 Tl scintigraphy is useful evaluating cardiac morphology as well as in diagnosing myocardial ischemia. (J.P.N.)

Extracellular signal-regulated kinases 1/2 as regulators of cardiac hypertrophy

Directory of Open Access Journals (Sweden)

Michael eMutlak

2015-07-01

Full Text Available Cardiac hypertrophy results from increased mechanical load on the heart and through the actions of local and systemic neuro-humoral factors, cytokines and growth factors. These mechanical and neuroendocrine effectors act through stretch, G protein-coupled receptors and tyrosine kinases to induce the activation of a myriad of intracellular signaling pathways including the extracellular signal-regulated kinases 1/2 (ERK1/2. Since most stimuli that provoke myocardial hypertrophy also elicit an acute phosphorylation of the threonine-glutamate-tyrosine (TEY motif within the activation loops of ERK1 and ERK2 kinases, resulting in their activation, ERKs have long been considered promotors of cardiac hypertrophy. Several mouse models were generated in order to directly understand the causal role of ERK1/2 activation in the heart. These models include direct manipulation of ERK1/2 such as overexpression, mutagenesis or knockout models, manipulations of upstream kinases such as MEK1 and manipulations of the phosphatases that depohosphorylate ERK1/2 such as DUSP6. The emerging understanding from these studies, as will be discussed here, is more complex than originally considered. While there is little doubt that ERK1/2 activation or the lack of it modulates the hypertrophic process or the type of hypertrophy that develops, it appears that not all ERK1/2 activation events are the same. While much has been learned, some questions remain regarding the exact role of ERK1/2 in the heart, the upstream events that result in ERK1/2 activation and the downstream effector in hypertrophy.

Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis.

Science.gov (United States)

Khangura, Jaspreet; Culleton, Bruce F; Manns, Braden J; Zhang, Jianguo; Barnieh, Lianne; Walsh, Michael; Klarenbach, Scott W; Tonelli, Marcello; Sarna, Magdalena; Hemmelgarn, Brenda R

2010-06-24

Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC). Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy. A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.

High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

Science.gov (United States)

Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

2013-01-01

The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

International Nuclear Information System (INIS)

Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

2010-01-01

Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and α-smooth muscle actin (α-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

Exploring Regulatory Mechanisms of Atrial Myocyte Hypertrophy of Mitral Regurgitation through Gene Expression Profiling Analysis: Role of NFAT in Cardiac Hypertrophy.

Directory of Open Access Journals (Sweden)

Tzu-Hao Chang

Full Text Available Left atrial enlargement in mitral regurgitation (MR predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown.This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD, and 6 purchased samples from normal subjects (NC. We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that "NFAT in cardiac hypertrophy" pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1 were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC.Differentially expressed genes in the "NFAT in cardiac hypertrophy" pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.

Second statement of the working group on electrocardiographic diagnosis of left ventricular hypertrophy

DEFF Research Database (Denmark)

Bacharova, Ljuba; Estes, E Harvey; Bang, Lia E

2011-01-01

The Working Group on Electrocardiographic Diagnosis of Left Ventricular Hypertrophy, appointed by the Editor of the Journal of Electrocardiology, presents the alternative conceptual model for the ECG diagnosis of left ventricular hypertrophy (LVH). It is stressed that ECG is a record of electrica...

Breast Hypertrophy, Reduction Mammaplasty, and Body Image.

Science.gov (United States)

Fonseca, Cristiane Costa; Veiga, Daniela Francescato; Garcia, Edgard da Silva; Cabral, Isaías Vieira; de Carvalho, Monique Maçais; de Brito, Maria José Azevedo; Ferreira, Lydia Masako

2018-02-07

Body image dissatisfaction is one of the major factors that motivate patients to undergo plastic surgery. However, few studies have associated body satisfaction with reduction mammaplasty. The aim of this study was to evaluate the impact of breast hypertrophy and reduction mammaplasty on body image. Breast hypertrophy patients, with reduction mammaplasty already scheduled between June 2013 and December 2015 (mammaplasty group, MG), were prospectively evaluated through the body dysmorphic disorder examination (BDDE), body investment scale (BIS), and breast evaluation questionnaire (BEQ55) tools. Women with normal-sized breasts were also evaluated as study controls (normal-sized breast group, NSBG). All the participants were interviewed at the initial assessment and after six months. Data were analyzed before and after six months. Each group consisted of 103 women. The MG group had a significant improvement in BDDE, BIS, and BEQ55 scores six months postoperatively (P ≤ 0.001 for the three instruments), whereas the NSBG group showed no alteration in results over time (P = 0.876; P = 0.442; and P = 0.184, respectively). In the intergroup comparison it was observed that the MG group began to invest more in the body, similarly to the NSBG group, and surpassed the level of satisfaction and body image that the women of the NSBG group had after the surgery. Reduction mammaplasty promoted improvement in body image of women with breast hypertrophy. © 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Capillarization and vascular endothelial growth factor expression in hypertrophying anterior latissimus dorsi muscle of the Japanese quail.

NARCIS (Netherlands)

Degens, H.; Anderson, R.K.; Alway, S.E.

2003-01-01

Hypertrophy may increase the diffusion distances from capillaries to the interior of the muscle fibers. We hypothesized that capillary proliferation occurs during hypertrophy, which is accompanied by an up-regulation of vascular endothelial growth factor (VEGF). Hypertrophy of the left anterior

Benazepril inhibited the NF-κB and TGF-β networking on LV hypertrophy in rats.

Science.gov (United States)

Yan, Shi-Hai; Zhao, Ning-Wei; Zhu, Xuan-Xuan; Wang, Qiong; Wang, Hai-Dan; Fu, Rui; Sun, Yuan; Li, Qi-Yi

2013-05-01

Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, has been used to treat hypertension, congestive heart failure, and chronic renal failure. However, its biological activity and mechanism of action in inflammation are not fully identified. The present study was designed to determine the in vivo anti-inflammatory effects of benazepril on LV hypertrophy in rats. LV hypertrophy was produced in rats by abdominal aortic coarctation. They were then divided into the following groups: sham operation; LV hypertrophy; LV hypertrophy+benazepril (1mg/kg in a gavage, once a day for 4 weeks). Both morphological assays (hemodynamic and hemorheological measurement; LV hypertrophy assessment), and molecular assays (protein levels of Collagen type I/III, TNF-α and VCAM-1; TGF-β gene expression; NF-κB or Smad activation; intracellular ROS production) were performed. The following effects were observed in rats treated with benazepril: (1) marked improvements in hemodynamic and hemorheological parameters; (2) significant reductions in LV hypertrophy, dilatation and fibrosis; (3) significantly attenuated protein levels of Collagen type I/III, TGF-β, TNF-α and VCAM-1, NF-κB or Smad activation, as well as intracellular ROS production. These results suggest that the anti-inflammatory properties of benazepril may be ascribed to their down-regulation of both NF-κB and TGF-β signaling pathways by acting on the intracellular ROS production in rats with LV hypertrophy, thus supporting the use of benazepril as an anti-inflammatory agent. Copyright © 2013 Elsevier B.V. All rights reserved.

Regional variations in HDL metabolism in human fat cells: effect of cell size

International Nuclear Information System (INIS)

Despres, J.; Fong, B.S.; Julien, P.; Jimenez, J.; Angel, A.

1987-01-01

Abdominal obesity is related to reduced plasma high-density lipoprotein (HDL) cholesterol, and both are associated with cardiovascular disease risk. The authors have observed that plasma membranes from abdominal subcutaneous adipocytes have a greater HDL binding capacity than omental fat cell plasma membranes. The present study examined whether these binding characteristics could be due to differences in fat cell size or cholesterol concentration between the two adipose depots. Abdominal subcutaneous and deep omental fat were obtained from massively obese patients at surgery. Subcutaneous abdominal fat cells were significantly larger and their cellular cholesterol content greater than omental adipocytes. The uptake of HDL by collagenase-isolated fat cells was studied by incubating the cells for 2 h at 37 0 C with 10 μg/ml 125 I-HDL 2 or 125 I-HDL 3 . In both depots, the cellular uptake of 125 I-HDL 2 and 125 I-HDL 3 was specifically inhibited by addition of 25-fold excess unlabeled HDL and a close correlation was observed between the cellular uptake of 125 I-HDL 2 and 125 I-HDL 3 . In obese patients, the uptake of 125 I-HDL was higher in subcutaneous cells than in omental cells. The cellular 125 I-HDL uptake was significantly correlated with adipocyte size and fat cell cholesterol content but not with adipocyte cholesterol concentration. These results suggest that the higher HDL uptake observed in subcutaneous cells compared with omental cells in obesity is the result of differences in adipocyte size rather than differences in the cholesterol concentration (cholesterol-to-triglyceride ratio). The increased interaction of HDL with hypertrophied abdominal adipocytes may play an important role in determining the lipid composition of HDL in obesity

Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis

Directory of Open Access Journals (Sweden)

Walsh Michael

2010-06-01

Full Text Available Abstract Background Left ventricular (LV hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. Methods This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month. Agreement was assessed using Lin's concordance correlation coefficient (CCC and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC. Results Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80 predictive power for LV hypertrophy. Conclusions A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.

Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice.

Science.gov (United States)

Kanwar, R K; Macgibbon, A K; Black, P N; Kanwar, J R; Rowan, A; Vale, M; Krissansen, G W

2008-01-01

It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses. C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

Left ventricular hypertrophy : virtuous intentions, malign consequences

NARCIS (Netherlands)

Pokharel, S; Sharma, UC; Pinto, YM

Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca2+ homeostasis, there

Left ventricular hypertrophy: virtuous intentions, malign consequences

NARCIS (Netherlands)

Pokharel, Saraswati; Sharma, Umesh C.; Pinto, Yigal M.

2003-01-01

Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there

Dietary obacunone supplementation stimulates muscle hypertrophy, and suppresses hyperglycemia and obesity through the TGR5 and PPARγ pathway

Energy Technology Data Exchange (ETDEWEB)

Horiba, Taro, E-mail: thoriba@mail.kikkoman.co.jp [Research and Development Division, Kikkoman Corporation, Chiba (Japan); Katsukawa, Masahiro [Research and Development Division, Kikkoman Corporation, Chiba (Japan); Mita, Moeko; Sato, Ryuichiro [Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo (Japan)

2015-08-07

Obacunone is a limonoid that is predominantly found in Citrus. Although various biological activities of limonoids have been reported, little is known about the beneficial effects of obacunone on metabolic disorders. In the present study, we examined the effects of dietary obacunone supplementation on obese KKAy mice, to clarify the function of obacunone in metabolic regulation. Mice were pair-fed a normal diet either alone or supplemented with 0.1% w/w obacunone for 28 days. Compared with the control, obacunone-fed mice had lower glycosylated hemoglobin, blood glucose, and white adipose tissue weight, although there was no significant difference in body weight. Obacunone treatment also significantly increased the weight of the gastrocnemius and quadriceps muscles. Reporter gene assays revealed that obacunone stimulated the transcriptional activity of the bile acids-specific G protein-coupled receptor, TGR5, in a dose-dependent manner. In addition, obacunone inhibited adipocyte differentiation in 3T3-L1 cells and antagonized ligand-stimulated peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity. These results suggest that obacunone stimulates muscle hypertrophy and prevents obesity and hyperglycemia, and that these beneficial effects are likely to be mediated through the activation of TGR5 and inhibition of PPARγ transcriptional activity. - Highlights: • Citrus limonoid obacunone prevents hyperglycemia in obese, diabetic KKAy mice. • Obacunone reduces fat content and stimulates muscle hypertrophy in KKAy mice. • Obacunone stimulates TGR5 transcriptional activities. • Obacunone antagonizes PPARγ and inhibits lipid accumulation in adipocytes.

Dietary obacunone supplementation stimulates muscle hypertrophy, and suppresses hyperglycemia and obesity through the TGR5 and PPARγ pathway

International Nuclear Information System (INIS)

Horiba, Taro; Katsukawa, Masahiro; Mita, Moeko; Sato, Ryuichiro

2015-01-01

Obacunone is a limonoid that is predominantly found in Citrus. Although various biological activities of limonoids have been reported, little is known about the beneficial effects of obacunone on metabolic disorders. In the present study, we examined the effects of dietary obacunone supplementation on obese KKAy mice, to clarify the function of obacunone in metabolic regulation. Mice were pair-fed a normal diet either alone or supplemented with 0.1% w/w obacunone for 28 days. Compared with the control, obacunone-fed mice had lower glycosylated hemoglobin, blood glucose, and white adipose tissue weight, although there was no significant difference in body weight. Obacunone treatment also significantly increased the weight of the gastrocnemius and quadriceps muscles. Reporter gene assays revealed that obacunone stimulated the transcriptional activity of the bile acids-specific G protein-coupled receptor, TGR5, in a dose-dependent manner. In addition, obacunone inhibited adipocyte differentiation in 3T3-L1 cells and antagonized ligand-stimulated peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity. These results suggest that obacunone stimulates muscle hypertrophy and prevents obesity and hyperglycemia, and that these beneficial effects are likely to be mediated through the activation of TGR5 and inhibition of PPARγ transcriptional activity. - Highlights: • Citrus limonoid obacunone prevents hyperglycemia in obese, diabetic KKAy mice. • Obacunone reduces fat content and stimulates muscle hypertrophy in KKAy mice. • Obacunone stimulates TGR5 transcriptional activities. • Obacunone antagonizes PPARγ and inhibits lipid accumulation in adipocytes

Thyroid hormone-induced hypertrophy in mesenchymal stem cell chondrogenesis is mediated by bone morphogenetic protein-4.

Science.gov (United States)

Karl, Alexandra; Olbrich, Norman; Pfeifer, Christian; Berner, Arne; Zellner, Johannes; Kujat, Richard; Angele, Peter; Nerlich, Michael; Mueller, Michael B

2014-01-01

Chondrogenic differentiating mesenchymal stem cells (MSCs) express markers of hypertrophic growth plate chondrocytes. As hypertrophic cartilage undergoes ossification, this is a concern for the application of MSCs in articular cartilage tissue engineering. To identify mechanisms that elicit this phenomenon, we used an in vitro hypertrophy model of chondrifying MSCs for differential gene expression analysis and functional experiments with the focus on bone morphogenetic protein (BMP) signaling. Hypertrophy was induced in chondrogenic MSC pellet cultures by transforming growth factor β (TGFβ) and dexamethasone withdrawal and addition of triiodothyronine. Differential gene expression analysis of BMPs and their receptors was performed. Based on these results, the in vitro hypertrophy model was used to investigate the effect of recombinant BMP4 and the BMP inhibitor Noggin. The enhancement of hypertrophy could be shown clearly by an increased cell size, alkaline phosphatase activity, and collagen type X deposition. Upon induction of hypertrophy, BMP4 and the BMP receptor 1B were upregulated. Addition of BMP4 further enhanced hypertrophy in the absence, but not in the presence of TGFβ and dexamethasone. Thyroid hormone induced hypertrophy by upregulation of BMP4 and this induced enhancement of hypertrophy could be blocked by the BMP antagonist Noggin. BMP signaling is an important modulator of the late differentiation stages in MSC chondrogenesis and the thyroid hormone induces this pathway. As cartilage tissue engineering constructs will be exposed to this factor in vivo, this study provides important insight into the biology of MSC-based cartilage. Furthermore, the possibility to engineer hypertrophic cartilage may be helpful for critical bone defect repair.

AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload.

Science.gov (United States)

Riedl, Isabelle; Osler, Megan E; Björnholm, Marie; Egan, Brendan; Nader, Gustavo A; Chibalin, Alexander V; Zierath, Juleen R

2016-03-15

Mechanisms regulating skeletal muscle growth involve a balance between the activity of serine/threonine protein kinases, including the mammalian target of rapamycin (mTOR) and 5'-AMP-activated protein kinase (AMPK). The contribution of different AMPK subunits to the regulation of cell growth size remains inadequately characterized. Using AMPKγ3 mutant-overexpressing transgenic Tg-Prkag3(225Q) and AMPKγ3-knockout (Prkag3(-/-)) mice, we investigated the requirement for the AMPKγ3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the γ3 isoform did not impair muscle growth, control sham-operated AMPKγ3-transgenic mice displayed heavier plantaris muscles in response to overload hypertrophy and underwent smaller mass gain and lower Igf1 expression compared with wild-type littermates. The mTOR signaling pathway was upregulated with functional overload but unchanged between genetically modified animals and wild-type littermates. Differences in AMPK-related signaling pathways between transgenic, knockout, and wild-type mice did not impact muscle hypertrophy. Glycogen content was increased following overload in wild-type mice. In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPKγ3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKγ3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy. Copyright © 2016 the American Physiological Society.

Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

Science.gov (United States)

Xu, Shouyu; Liu, Xueyun; Chen, Zhenhuang; Li, Gaoquan; Chen, Qin; Zhou, Guoqing; Ma, Ruijie; Yao, Xinmiao; Huang, Xiao

2016-12-15

Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomechanical implications of skeletal muscle hypertrophy and atrophy: a musculoskeletal model

Directory of Open Access Journals (Sweden)

Andrew D. Vigotsky

2015-11-01

Full Text Available Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-sectional area (ACSA of a muscle and its MA length. In the model, the ACSAs of the biceps brachii and brachialis were altered to hypertrophy up to twice their original size and to atrophy to one-half of their original size. The change in MA length was found to be proportional to the arcsine of the square root of the change in ACSA. This change in MA length may be a small but important contributor to strength, especially in sports that require large joint moments at slow joint angular velocities, such as powerlifting. The paradoxical implications of the increase in MA are discussed, as physiological factors influencing muscle contraction velocity appear to favor a smaller MA length for high velocity movements but a larger muscle MA length for low velocity, high force movements.

VO(2peak), myocardial hypertrophy, and myocardial blood flow in endurance-trained men.

Science.gov (United States)

Laaksonen, Marko S; Heinonen, Ilkka; Luotolahti, Matti; Knuuti, Juhani; Kalliokoski, Kari K

2014-08-01

Endurance training induces cardiovascular and metabolic adaptations, leading to enhanced endurance capacity and exercise performance. Previous human studies have shown contradictory results in functional myocardial vascular adaptations to exercise training, and we hypothesized that this may be related to different degrees of hypertrophy in the trained heart. We studied the interrelationships between peak aerobic power (V˙O2peak), myocardial blood flow (MBF) at rest and during adenosine-induced vasodilation, and parameters of myocardial hypertrophy in endurance-trained (ET, n = 31) and untrained (n = 17) subjects. MBF and myocardial hypertrophy were studied using positron emission tomography and echocardiography, respectively. Both V˙O2peak (P negatively with adenosine-stimulated MBF, but when LV mass was taken into account as a partial correlate, this correlation disappeared. The present results show that increased LV mass in ET subjects explains the reduced hyperemic myocardial perfusion in this subject population and suggests that excessive LV hypertrophy has negative effect on cardiac blood flow capacity.

Unilateral hypertrophy of tensor fascia lata: a soft tissue tumor simulator

Energy Technology Data Exchange (ETDEWEB)

Ilaslan, H. [Department of Radiology, Mayo Clinic, 200 First Street, 55905, SW Rochester, MN (United States); Department of Radiology A21, Cleveland Clinic, Cleveland, OH (United States); Wenger, D.E. [Department of Radiology, Mayo Clinic, 200 First Street, 55905, SW Rochester, MN (United States); Shives, T.C. [Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN (United States); Unni, K.K. [Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN (United States)

2003-11-01

To describe the imaging findings in eight cases of unilateral tensor fascia lata (TFL) hypertrophy presenting as soft tissue masses. Imaging studies and medical charts of eight patients were reviewed retrospectively. The imaging studies included five radiographs, five computed tomography (CT) and six magnetic resonance imaging (MRI) examinations. The majority of patients (seven of eight) presented with a palpable proximal anterior thigh mass. One patient was asymptomatic and incidentally diagnosed. There were six females and two males. Ages ranged from 27 to 86 years old (mean 61). MRI and CT showed unilateral enlargement of the TFL muscle in all cases. TFL muscle hypertrophy is an uncommon clinical entity, which can simulate a soft tissue tumor. The characteristic appearance on CT or MRI allows a confident diagnosis of muscle hypertrophy to be made, avoiding unnecessary biopsy or surgical intervention. (orig.)

Unilateral hypertrophy of tensor fascia lata: a soft tissue tumor simulator

International Nuclear Information System (INIS)

Ilaslan, H.; Wenger, D.E.; Shives, T.C.; Unni, K.K.

2003-01-01

To describe the imaging findings in eight cases of unilateral tensor fascia lata (TFL) hypertrophy presenting as soft tissue masses. Imaging studies and medical charts of eight patients were reviewed retrospectively. The imaging studies included five radiographs, five computed tomography (CT) and six magnetic resonance imaging (MRI) examinations. The majority of patients (seven of eight) presented with a palpable proximal anterior thigh mass. One patient was asymptomatic and incidentally diagnosed. There were six females and two males. Ages ranged from 27 to 86 years old (mean 61). MRI and CT showed unilateral enlargement of the TFL muscle in all cases. TFL muscle hypertrophy is an uncommon clinical entity, which can simulate a soft tissue tumor. The characteristic appearance on CT or MRI allows a confident diagnosis of muscle hypertrophy to be made, avoiding unnecessary biopsy or surgical intervention. (orig.)

Repeated blood flow restriction induces muscle fiber hypertrophy.

Science.gov (United States)

Sudo, Mizuki; Ando, Soichi; Kano, Yutaka

2017-02-01

We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy. Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross-sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks. CSA was greater in the BFR+ECC group than in the CONT (P muscle fiber hypertrophy at the cellular level. Muscle Nerve 55: 274-276, 2017. © 2016 Wiley Periodicals, Inc.

GSK-3β/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy.

Directory of Open Access Journals (Sweden)

Javier Duran

Full Text Available Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis. Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results

Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

Directory of Open Access Journals (Sweden)

Xiao-Bing Ji

2015-07-01

Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring

Directory of Open Access Journals (Sweden)

Stephanie A. Segovia

2018-03-01

Full Text Available Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl, high-salt (SD; 10% kcal from fat, 4% NaCl, high-fat (HF; 45% kcal from fat, 1% NaCl or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl diets 21 days prior to mating and throughout pregnancy and lactation. Male offspring were weaned onto a standard chow diet and were culled on postnatal day 130 for plasma and tissue collection. Adipocyte histology and adipose tissue, liver, and gut gene expression were examined in adult male offspring. HF offspring had significantly greater body weight, impaired insulin sensitivity and hyperleptinemia compared to CD offspring, but these increases were blunted in HFSD offspring. HF offspring had moderate adipocyte hypertrophy and increased expression of the pre-adipocyte marker Dlk1. There was a significant effect of maternal salt with increased hepatic expression of Dgat1 and Igfb2. Gut expression of inflammatory (Il1r1, Tnfα, Il6, and Il6r and renin–angiotensin system (Agtr1a, Agtr1b markers was significantly reduced in HFSD offspring compared to HF offspring. Therefore, salt mitigates some adverse offspring outcomes associated with a maternal HF diet, which may be mediated by altered adipose tissue morphology and gut inflammatory and renin–angiotensin regulation.

SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle.

Science.gov (United States)

Koltai, Erika; Bori, Zoltán; Chabert, Clovis; Dubouchaud, Hervé; Naito, Hisashi; Machida, Shuichi; Davies, Kelvin Ja; Murlasits, Zsolt; Fry, Andrew C; Boldogh, Istvan; Radak, Zsolt

2017-06-01

Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways.

Science.gov (United States)

Cao, Zhen; Dou, Ce; Dong, Shiwu

2017-01-01

Using tissue engineering technique to repair cartilage damage caused by osteoarthritis is a promising strategy. However, the regenerated tissue usually is fibrous cartilage, which has poor mechanical characteristics compared to hyaline cartilage. Chondrocyte hypertrophy plays an important role in this process. Thus, it is very important to find out a suitable way to maintain the phenotype of chondrocytes and inhibit chondrocyte hypertrophy. Curcumin deriving from turmeric was reported with anti-inflammatory and anti-tumor pharmacological effects. However, the role of curcumin in metabolism of chondrocytes, especially in the chondrocyte hypertrophy remains unclear. Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering as seed cells. So we investigated the effect of curcumin on chondrogenesis and chondrocyte hypertrophy in MSCs through examination of cell viability, glycosaminoglycan synthesis and specific gene expression. We found curcumin had no effect on expression of chondrogenic markers including Sox9 and Col2a1 while hypertrophic markers including Runx2 and Col10a1 were down-regulated. Further exploration showed that curcumin inhibited chondrocyte hypertrophy through Indian hedgehog homolog (IHH) and Notch signalings. Our results indicated curcumin was a potential agent in modulating cartilage homeostasis and maintaining chondrocyte phenotype.

Hypertrophy of cultured bovine aortic endothelium following irradiation

International Nuclear Information System (INIS)

Rosen, E.M.; Vinter, D.W.; Goldberg, I.D.

1989-01-01

The vascular endothelium is a vital multifunctional tissue which covers the entire luminal surface of the circulatory system. Loss of continuity of the endothelial lining normally results in cell migration and proliferation to make up for cell loss and to ensure that exposure of the thrombogenic subendothelium to platelets and clotting factors is minimized. We showed that ionizing radiation (400-3000 cGy) causes dose-dependent cell loss from confluent monolayer cultures of bovine aortic endothelium, which cannot immediately be compensated by cell proliferation. Within 24 h, the remaining attached cells undergo substantial somatic hypertrophy (evidenced by increased protein content, cell volume, and attachment area) but remain diploid. If cell loss is not excessive, monolayer continuity is restored within several days. Although reduced protein degradation may contribute, most of the protein accumulation is due to synthesis of new protein. Unlike endothelium, irradiation of smooth muscle cultures causes neither cell loss nor increased protein synthesis. Hypertrophy of irradiated endothelial cells appears to be a consequence of a proliferative stimulus (cell loss) in a population of cells which is unable to divide. It can be modulated by replating irradiated cells at different densities. We suggest that endothelial hypertrophy is an early vascular homeostatic response before clonal proliferation of surviving cells or repopulation by cells from outside of the irradiated field can compensate for cell loss

Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.

Directory of Open Access Journals (Sweden)

Liming Pan

Full Text Available This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418 on cardiac hypertrophy caused by aortic banding (AB, phenylephrine (PE or angiotensin II (Ang II in vivo and in vitro.The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM or hypertrophic cardiomyopathy (HCM and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting.ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro.ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

Myocardial hypertrophy and intracardial hemodynamics in children with bicuspid aortic valve

Directory of Open Access Journals (Sweden)

А. V. Kamenshchyk

2017-08-01

Full Text Available Bicuspid aortic valve is one of the most common congenital heart diseases with low manifestation in childhood and severe consequences in adults that determines the importance in early diagnostics of myocardial changes in this anomaly. According to the literature the polymorphisms in the genes of NFATC family could result both in impaired embriogenetic valves formation and development of postnatal myocardial hypertrophy. The aim of the study was to detect the early changes of intracardial hemodynamics at aortic valve in children with bicuspid aortic valve (BAV and establish their interrelations to the signs of myocardial hypertrophy in these children. Materials and methods: Dopplerograhphic study of basic intracardiac hemodynamics parameters in 38 children with BAV and in 28 children of control group was conducted. The results were processed statistically by Student’s t-test, correlation analysis and multiple regression. Results: In the result of study the moderate concentric left ventricle myocardial hypertrophy development was detected in 62 % of children with BAV which is accompanying to significant increasing of blood flow velocity and pressure gradient at aortic valve. There were not established significant correlations between the parameters of hemodynamics at valve and left ventricle’s posterior wall depth and septum depth whereas the highest inputs of these values were obtained in the left ventricle systolic dimension and volume and less in the hypertrophic signs. Conclusions: In children with BAV the moderate concentric myocardial hypertrophy with significant changes of intracardial hemodynamics at aortic valve takes place with the highest inputs in left ventricle volumetric values The obtained data serves as a substantiation for the treatment and prevention of it further development. bicuspid aortic valve; children; heart hypertrophy; dopplerechocardiography; hemodynamics; regression analysis

Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.

Science.gov (United States)

Herbach, Nadja; Schairer, Irene; Blutke, Andreas; Kautz, Sabine; Siebert, Angela; Göke, Burkhard; Wolf, Eckhard; Wanke, Ruediger

2009-04-01

Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.

Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition.

Science.gov (United States)

Parikh, Victoria Nicole; Liu, Jing; Shang, Ching; Woods, Christopher; Chang, Alex Chia Yu; Zhao, Mingming; Charo, David N; Grunwald, Zachary; Huang, Yong; Seo, Kinya; Tsao, Philip S; Bernstein, Daniel; Ruiz-Lozano, Pilar; Quertermous, Thomas; Ashley, Euan A

2018-05-18

The G protein coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJ endo-/- ) and myocardium (APJ myo-/- ). No baseline difference was observed in LV function in APJ endo-/- , APJ myo-/- or controls (APJ endo+/+ , APJ myo+/+ ). After exposure to transaortic constriction (TAC), APJ endo-/- animals developed left ventricular failure while APJ myo-/- were protected. At the cellular level, carbon fiber stretch of freshly isolated single cardiomyocytes demonstrated decreased contractile response to stretch in APJ -/- cardiomyocytes compared to APJ +/+ cardiomyocytes. Calcium transient did not change with stretch in either APJ -/- or APJ +/+ cardiomyocytes. Application of apelin to APJ +/+ cardiomyocytes resulted in decreased calcium transient. Further, hearts of mice treated with apelin exhibited decreased phosphorylation at Troponin I (cTnI) N-terminal residues (Ser 22,23), consistent with increased calcium sensitivity. These data establish that APJ stretch transduction is mediated specifically by myocardial APJ, that APJ is necessary for stretch-induced increases in contractility, and that apelin opposes APJ's stretch-mediated hypertrophy signaling by lowering calcium transient while maintaining contractility through myofilament calcium sensitization. These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition.

Association of heart failure hospitalizations with combined electrocardiography and echocardiography criteria for left ventricular hypertrophy

DEFF Research Database (Denmark)

Gerdts, Eva; Okin, Peter M; Boman, Kurt

2012-01-01

The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain.......The value of performing echocardiography in hypertensive patients with electrocardiographic left ventricular hypertrophy (LVH) is uncertain....

Effect of prophylactic digitalization on the development of myocardial hypertrophy.

Science.gov (United States)

Cutilletta, A F; Rudnik, M; Arcilla, R A; Straube, R

1977-11-01

The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

Malondialdehyde in benign prostate hypertrophy: a useful marker?

Directory of Open Access Journals (Sweden)

Rosaria Alba Merendino

2003-01-01

Full Text Available Benign prostate hypertrophy (BPH is the most common benign tumor in men due to obstruction of the urethra and, finally, uremia. Malondialdehyde (MDA is a product derived from peroxidation of polyunsaturated fatty acids and related esters. Evaluation of MDA in serum represents a non-invasive biomarker of oxidative stress. Prostate-specific antigen (PSA is a sensitive marker for prostatic hypertrophy and cancer. We analyzed MDA serum levels to evaluate the oxidative stress in BPH. To this end, 22 BPH patients and 22 healthy donors were enrolled. Data show an increase of MDA level in BPH patients and a positive correlation between PSA and MDA levels. In conclusion, we describe a previously unknown relationship between PSA and MDA as an index of inflammation and oxidative stress in BPH.

Improved bioavailability of targeted Curcumin delivery efficiently regressed cardiac hypertrophy by modulating apoptotic load within cardiac microenvironment

International Nuclear Information System (INIS)

Ray, Aramita; Rana, Santanu; Banerjee, Durba; Mitra, Arkadeep; Datta, Ritwik; Naskar, Shaon; Sarkar, Sagartirtha

2016-01-01

Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5 mg/kg body weight compared to free Curcumin at 35 mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, β-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. - Highlights: • Cardiomyocyte targeted Curcumin/CMC-peptide increases bioavailability of the drug. �

Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

Science.gov (United States)

Tagawa, H.; Koide, M.; Sato, H.; Zile, M. R.; Carabello, B. A.; Cooper, G. 4th

1998-01-01

Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.

Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy.

Science.gov (United States)

Luckey, Stephen W; Haines, Chris D; Konhilas, John P; Luczak, Elizabeth D; Messmer-Kratzsch, Antke; Leinwand, Leslie A

2017-12-01

A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1 -/- ), and mice deficient in cyclin D2 (cyclin D2 -/- ). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2 -/- mice. Cardiac function was not impacted in the cyclin D2 -/- mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2 -/- mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise

Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study

DEFF Research Database (Denmark)

Wachtell, Kristian; Okin, Peter M; Olsen, Michael H

2007-01-01

BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertens......BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction...... risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy. Udgivelsesdato: 2007-Aug-14...

Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.

Science.gov (United States)

Khalilimeybodi, Ali; Daneshmehr, Alireza; Sharif-Kashani, Babak

2018-07-01

The chronic stimulation of β-adrenergic receptors plays a crucial role in cardiac hypertrophy and its progression to heart failure. In β-adrenergic signaling, in addition to the well-established classical pathway, Gs/AC/cAMP/PKA, activation of non-classical pathways such as Gi/PI3K/Akt/GSK3β and Gi/Ras/Raf/MEK/ERK contribute in cardiac hypertrophy. The signaling network of β-adrenergic-induced hypertrophy is very complex and not fully understood. So, we use a computational approach to investigate the dynamic response and contribution of β-adrenergic mediators in cardiac hypertrophy. The proposed computational model provides insights into the effects of β-adrenergic classical and non-classical pathways on the activity of hypertrophic transcription factors CREB and GATA4. The results illustrate that the model captures the dynamics of the main signaling mediators and reproduces the experimental observations well. The results also show that despite the low portion of β2 receptors out of total cardiac β-adrenergic receptors, their contribution in the activation of hypertrophic mediators and regulation of β-adrenergic-induced hypertrophy is noticeable and variations in β1/β2 receptors ratio greatly affect the ISO-induced hypertrophic response. The model results illustrate that GSK3β deactivation after β-adrenergic receptor stimulation has a major influence on CREB and GATA4 activation and consequent cardiac hypertrophy. Also, it is found through sensitivity analysis that PKB (Akt) activation has both pro-hypertrophic and anti-hypertrophic effects in β-adrenergic signaling.

Left ventricular hypertrophy: virtuous intentions, malign consequences.

Science.gov (United States)

Pokharel, Saraswati; Sharma, Umesh C; Pinto, Yigal M

2003-06-01

Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there are structural changes in myofilaments, disorganization of the cytoskeletal framework and increased collagen synthesis. LVH is associated with progressive left ventricular remodeling that culminates to heart failure. The modern treatment of left ventricular hypertrophy is now largely based on the hypothesis that neuroendocrine activation is important in the progression of the disease and inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Drugs specifically designed to unload the left ventricle, such as diuretics and vasodilators, appears to be less effective in reducing LV mass and improving prognosis. Thus, the evolution of treatment for LVH itself has provided much enlightenment for our understanding of the fundamental biology of the disorder.

Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

Science.gov (United States)

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization

Science.gov (United States)

Hixon, Mary L.; Muro-Cacho, Carlos; Wagner, Mark W.; Obejero-Paz, Carlos; Millie, Elise; Fujio, Yasushi; Kureishi, Yasuko; Hassold, Terry; Walsh, Kenneth; Gualberto, Antonio

2000-01-01

Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure–dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell–cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension. PMID:11032861

The characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy

International Nuclear Information System (INIS)

Isobe, Naoki; Toyama, Takuji; Hoshizaki, Hiroshi

1999-01-01

We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with 123 I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting 201 Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced 201 Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy. (author)

Classification of Hypertrophy of Labia Minora: Consideration of a Multiple Component Approach.

Science.gov (United States)

González, Pablo I

2015-11-01

Labia minora hypertrophy of unknown and under-reported incidence in the general population is considered a variant of normal anatomy. Its origin is multi-factorial including genetic, hormonal, and infectious factors, and voluntary elongation of the labiae minorae in some cultures. Consults with patients bothered by this condition have been increasing with patients complaining of poor aesthetics and symptoms such as difficulty with vaginal secretions, vulvovaginitis, chronic irritation, and superficial dyspareunia, all of which can have a negative effect on these patients' sexuality and self esteem. Surgical management of labial hypertrophy is an option for women with these physical complaints or aesthetic issues. Labia minora hypertrophy can consist of multiple components, including the clitoral hood, lateral prepuce, frenulum, and the body of the labia minora. To date, there is not a consensus in the literature with respect to the classification and definition of varying grades of hypertrophy, aside from measurement of the length in centimeters. In order to offer patients the most appropriate surgical technique, an objective and understandable classification that can be used as part of the preoperative evaluation is necessary. Such a classification should have the aim of offering patients the best cosmetic and functional results with the fewest complications.

Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

Science.gov (United States)

Moriya, Nobuki; Miyazaki, Mitsunori

2018-02-14

Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

Lumbar radiculopathy due to unilateral facet hypertrophy following lumbar disc hernia operation: a case report.

Science.gov (United States)

Kökeş, Fatih; Günaydin, Ahmet; Aciduman, Ahmet; Kalan, Mehmet; Koçak, Halit

2007-10-01

To present a radiculopathy case due to unilateral facet hypertrophy developing three years after a lumbar disc hernia operation. A fifty two-year-old female patient, who had been operated on for a left L5-S1 herniated lumbar disc three years ago, was hospitalized and re-operated with a diagnosis of unilateral facet hypertrophy. She had complaints of left leg pain and walking restrictions for the last six months. Left Straight Leg Raising test was positive at 40 degrees , left ankle dorsiflexion muscle strength was 4/5, left Extensor Hallucis Longus muscle strength was 3/5, and left Achilles reflex was hypoactive. Lumbar spinal Magnetic Resonance Imaging revealed left L5-S1 facet hypertrophy. Lumbar radiculopathy due to lumbar facet hypertrophy is a well-known neurological condition. Radicular pain develops during the late postoperative period following lumbar disc hernia operations that are often related to recurrent disc herniation or to formation of post-operative scar tissue. In addition, it can be speculated that unilateral facet hypertrophy, which may develop after a disc hernia operation, might also be one of the causes of radiculopathy.

Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2

DEFF Research Database (Denmark)

Witting, Nanna; Duno, M; Vissing, J

2013-01-01

Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic......, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest...

Evaluation of CT findings for diagnosis of pleural effusions

International Nuclear Information System (INIS)

Arenas-Jimenez, J.; Alonso-Charterina, S.; Fernandez-Latorre, F.; Gil-Sanchez, S.; Sanchez-Paya, J.; Lloret-Llorens, M.

2000-01-01

Computed tomography studies are usually used to assess patients with pleural effusions, and radiologists should be aware of the significance of different CT findings for the diagnosis of the effusion. The purpose of this study was to evaluate CT findings for etiological diagnosis of pleural effusions. Contrast-enhanced CT of the chest of 211 patients with pleural effusion of definite diagnosis were evaluated. The CT images were evaluated for the presence and extent of pleural effusion, thickening or nodules, extrapleural fat and other changes in the mediastinum or lung. The CT scans were read by two independent observers and correlation between them was evaluated. Comparison of CT findings between benign and malignant effusions, between exudates and transudates, and between empyemas and the other parapneumonic effusions were carried out. Kappa values for most CT findings were >0.85. Loculation, pleural thickening, pleural nodules, and extrapleural fat of increased density were only present in exudative effusions. Multiple pleural nodules and nodular pleural thickening were the only pleural findings limited to malignant pleural effusions. The signs were also more frequently seen in empyemas than in other parapneumonic effusions. Computed tomography findings can help to distinguish between transudates and exudates. Although there is some overlap between benign and malignant pleural effusions, pleural nodules and nodular pleural thickening were present almost exclusively in the latter. Although differences between CT findings of empyemas and the other parapneumonic effusions exist, there is no finding which can definitely differentiate between them. (orig.)

Airway evaluation by indirect laryngoscopy in patients with lingual tonsillar hypertrophy.

Science.gov (United States)

Sánchez-Morillo, Jorge; Gómez-Diago, Lorena; Rodríguez-Gimillo, Pablo; Herrera-Collado, Raúl; Puchol-Castillo, Jorge; Mompó-Romero, Luis

2013-01-01

Prevalence of the lingual tonsillar hypertrophy is unknown but it is believed that its presence is associated with the difficult airway. To investigate this, indirect laryngoscopy was performed on patients in the preoperative evaluation and this pathology was diagnosed. The relationship with difficulty of viewing the larynx, intubation and ventilation, under general anaesthesia and using direct laryngoscopy, was then studied. We performed the demographic variable checks and tests for predicting difficult intubation (mouth opening, thyromental distance, cervical flexion-extension, neck thickness and Mallampati test), in the preoperative step on 300 patients who were going to be submitted to general anaesthesia. We then performed indirect laryngoscopy on them using a 70° rigid laryngoscope to ascertain the frequency of appearance of lingual tonsillar hypertrophy. Next, under general anaesthesia, we carried out direct laryngoscopy to verify whether there was difficulty in viewing the larynx and intubation and ventilation. We then investigated the association of demographic predictors of difficult intubation, including indirect laryngoscopy, with the presence of this condition. Prevalence of lingual tonsillar hypertrophy was 2%. No relationship between the appearance of this entity and the difficulty of viewing the larynx, intubation and ventilation was found. Only indirect laryngoscopy was linked to the appearance of this pathology. Lingual tonsillar hypertrophy is a relatively frequent disorder, whose presence is not usually associated with difficult airway. Copyright © 2012 Elsevier España, S.L. All rights reserved.

The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

Directory of Open Access Journals (Sweden)

Leilei Zhong

2015-08-01

Full Text Available Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA. Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP/Transforming growth factor-β (TGFβ, Parathyroid hormone-related peptide (PTHrP, Indian hedgehog (IHH, Fibroblast growth factor (FGF, Insulin like growth factor (IGF and Hypoxia-inducible factor (HIF. This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.

Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

Science.gov (United States)

Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa

2013-01-01

Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (pmuscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.

Recognition of regional hypertrophy in hypertrophic cardiomyopathy using thallium-201 emission-computed tomography: comparison with two-dimensional echocardiography

International Nuclear Information System (INIS)

Suzuki, Y.; Kadota, K.; Nohara, R.

1984-01-01

The configuration of the hypertrophied myocardium was evaluated by thallium-201 emission-computed tomography and 2-dimensional (2-D) sector scan in 10 patients with obstructive hypertrophic cardiomyopathy (HC), 10 with nonobstructive HC with giant negative T waves and 10 with concentric left ventricular (LV) hypertrophy. Thallium-201 myocardial imaging was reconstructed into multiple 12-mm-thick slices in 3 planes. The thickness ratio of the ventricular septum and the LV posterior wall in the short-axis plane and the ratio of the ventricular septum and the apical wall in the long-axis plane were analyzed. In the patients with obstructive HC the ventricular septal wall thickness index was increased, and the ratio of septal to posterior wall thickness index (1.45 +/- 0.23) was greater than that in the patients with nonobstructive HC with giant negative T waves or in those with concentric LV hypertrophy (1.03 +/- 0.20 and 0.98 +/- 0.11, respectively; p less than 0.01 for each). In the patients with nonobstructive HC with giant negative T waves, increased apical wall thickness with apical cavity obliteration was characteristic, and the ratio of ventricular septal to apical wall thickness index (0.66 +/- 0.14) was less than that in the patients with obstructive HC or in those with concentric LV hypertrophy (1.46 +/- 0.38 and 1.04 +/- 0.09, respectively; p less than 0.001 for each). In contrast, technically satisfactory 2-D sector scanning (83%) demonstrated various configurations of the hypertrophied ventricularseptum, but could not detect apical hypertrophy in 4 of the 10 patients with nonobstructive HC with giant negative T waves whose LV cineangiograms demonstrated apical hypertrophy. Thus, thallium-201 emission-computed tomography is useful in evaluating the characteristics of LV hypertrophy and assists 2-D sector scan, especially in patients with apical hypertrophy in HC

How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+ pumps are crucial.

Science.gov (United States)

Blaustein, Mordecai P

2017-11-01

Left ventricular hypertrophy is frequently observed in hypertensive patients and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically engineered Na + pumps, however, have demonstrated that cardiac ouabain-sensitive α 2 -Na + pumps play a key role in the pathogenesis of transaortic constriction-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α 2 -Na + pumps and in mice with cardiac-selective knockout or transgenic overexpression of α 2 -Na + pumps. The latter, seemingly paradoxical, findings can be explained by comparing the numbers of available (ouabain-free) high-affinity (α 2 ) ouabain-binding sites in wild-type, knockout, and transgenic hearts. Conversely, hypertrophy was accelerated in α 2 -ouabain-resistant (R) mice in which the normally ouabain-resistant α 1 -Na + pumps were mutated to an ouabain-sensitive (S) form (α 1 S/S α 2 R/R or "SWAP" vs. wild-type or α 1 R/R α 2 S/S mice). Furthermore, transaortic constriction-induced hypertrophy in SWAP mice was prevented/reversed by immunoneutralizing circulating endogenous ouabain (EO). These findings show that EO and its receptor, ouabain-sensitive α 2 , are critical factors in pressure overload-induced cardiac hypertrophy. This complements reports linking elevated plasma EO to hypertension, cardiac hypertrophy, and failure in humans and elucidates the underappreciated role of the EO-Na + pump pathway in cardiovascular disease. Copyright © 2017 the American Physiological Society.

Ventricular premature contraction in hypertrophic cardiomyopathy and essential hypertension with left ventricular hypertrophy

International Nuclear Information System (INIS)

Kobiki, Naoki

1989-01-01

In order to investigate the relationship of different morbid states of the hypertrophied myocardium to the appearance of ventricular premature contraction (VPC), we compared the VPC findings from Holter ECG with those of UCG and stress thallium-201 myocardial SPECT scintigraphy (stress scinti) in 31 patients with hypertrophic cardiomyopathy (HCM) and 20 with essential hypertension (HT). The HCM patients consisted of 21 with asymmetric hypertrophy (ASH), 3 with symmetric hypertrophy (SH), and 7 with apical hypertrophy (APH). We recognized positive findings on the stress scinti such as fixed perfusion defect (FD) or reversible perfusion defect (RD) in 11 patients (ASH 10, APH 1) out of 31 patients with HCM (35%). Positive findings were observed in only one patient out of 20 with HT (5%). We recognized a high grade VPC (grade 4a and 4b of Lown's criteria) in 8 of 11 scinti positive patients with HCM (ASH 7, APH 1)(73%), while high grade VPC appeared in 5 (all of them are ASH) out of 20 scinti negative patients with HCM (25%). Therefore, these findings suggest that high grade VPCs in HCM occur in relation to a myocardial perfusion defect. (author)

Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block

NARCIS (Netherlands)

van Borren, Marcel M. G. J.; Vos, Marc A.; Houtman, Marien J. C.; Antoons, Gudrun; Ravesloot, Jan H.

2013-01-01

Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na+ influx in hypertrophied cAVB ventricular myocytes

Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

Directory of Open Access Journals (Sweden)

Chiaki Nagai-Okatani

Full Text Available Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

Effect of parathyroid hormone-related protein in an in vitro hypertrophy model for mesenchymal stem cell chondrogenesis.

Science.gov (United States)

Mueller, Michael B; Fischer, Maria; Zellner, Johannes; Berner, Arne; Dienstknecht, Thomas; Kujat, Richard; Prantl, Lukas; Nerlich, Michael; Tuan, Rocky S; Angele, Peter

2013-05-01

Mesenchymal stem cells (MSCs) express markers of hypertrophic chondrocytes during chondrogenic differentiation. We tested the suitability of parathyroid hormone-related protein (PTHrP), a regulator of chondrocyte hypertrophy in embryonic cartilage development, for the suppression of hypertrophy in an in vitro hypertrophy model of chondrifying MSCs. Chondrogenesis was induced in human MSCs in pellet culture for two weeks and for an additional two weeks cultures were either maintained in standard chondrogenic medium or transferred to a hypertrophy-enhancing medium. PTHrP(1-40) was added to the medium throughout the culture period at concentrations from 1 to 1,000 pM. Pellets were harvested on days one, 14 and 28 for biochemical and histological analysis. Hypertrophic medium clearly enhanced the hypertrophic phenotype, with increased cell size, and strong alkaline phosphatase (ALP) and type X collagen staining. In chondrogenic medium, 1-100 pM PTHrP(1-40) did not inhibit chondrogenic differentiation, whereas 1,000 pM PTHrP(1-40) significantly reduced chondrogenesis. ALP activity was dose-dependently reduced by PTHrP(1-40) at 10-1,000 pM in chondrogenic conditions. Under hypertrophy-enhancing conditions, PTHrP(1-40) did not inhibit the induction of the hypertrophy. At the highest concentration (1,000 pM) in the hypertrophic group, aggregates were partially dedifferentiated and differentiated areas of these aggregates maintained their hypertrophic appearance. PTHrP(1-40) treatment dose-dependently reduced ALP expression in MSC pellets cultured under standard chondrogenic conditions and is thus beneficial for the maintenance of the chondrogenic phenotype in this medium condition. When cultured under hypertrophy-enhancing conditions, PTHrP(1-40) could not diminish the induced enhancement of hypertrophy in the MSC pellets.

Novel Sulfur Metabolites of Garlic Attenuate Cardiac Hypertrophy and Remodeling through Induction of Na+/K+-ATPase Expression.

Science.gov (United States)

Khatua, Tarak N; Borkar, Roshan M; Mohammed, Soheb A; Dinda, Amit K; Srinivas, R; Banerjee, Sanjay K

2017-01-01

Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. However, the molecular basis for the beneficial effect of garlic on the heart is not known. Therefore, the objective of the present study was to (1) investigate the effect of raw garlic on isoproterenol (Iso) induced cardiac hypertrophy (2) find the active metabolites of garlic responsible for the beneficial effect. Cardiac hypertrophy was induced in rats by subcutaneous single injection of Iso 5 mg kg -1 day -1 for 15 days and the effect of garlic (250 mg/kg/day orally) was evaluated. Garlic metabolites in in vivo were identified by LC/MS study. The effect of garlic and its metabolites were evaluated against hypertrophy in H9C2 cells. Garlic normalized cardiac oxidative stress after Iso administration. Cardiac pathology and mitochondrial enzyme activities were improved in hypertrophy heart after garlic administration. Decreased Na + /K + -ATPase protein level that observed in hypertrophy heart was increased after garlic administration. We identified three garlic metabolites in rat serum. To confirm the role of garlic metabolites on cardiac hypertrophy, Na + /K + -ATPase expression and intracellular calcium levels were measured after treating H9C2 cells with raw garlic and two of its active metabolites, allyl methyl sulfide and allyl methyl sulfoxide. Raw garlic and both metabolites increased Na + /K + -ATPase protein level and decreased intracellular calcium levels and cell size in Iso treated H9C2 cells. This antihypertrophic effect of garlic and its sulfur metabolites were lost in H9C2 cells in presence of Na + /K + -ATPase inhibitor. In conclusion, garlic and its active metabolites increased Na + /K + -ATPase in rat heart, and attenuated cardiac hypertrophy and associated remodeling. Our data suggest that identified new garlic metabolites may be useful for therapeutic intervention against cardiac hypertrophy.

Effect of Thymol on Serum Antioxidant Capacity of Rats Following Myocardial Hypertrophy

Directory of Open Access Journals (Sweden)

Mohabbat Jamhiri

2017-07-01

Full Text Available Abstract Background: Oxidative stress plays an important role in the pathogenesis of hypertension- induced cardiac hypertrophy. Plants are a rich source of antioxidant compounds. Thymol is a natural monoterpen phenol which is plentiful in some plants and shows many biological effects. The aim of the present study was to assess the effects of thymol on activity of antioxidant enzyme catalase, malondialdehyde (MDA level and the activity of the inhibition of free radical DPPH (2,2-Diphenyl-1-picryl-hydrazyl, following left ventricular hypertrophy in rats. Materials and Methods: In this experimental study, rats were divided into hypertrophied group without any treatment (H group and rats pretreated with 25 and 50 mg/kg/day of thymol (Thy25+H and Thy50+H groups, respectively. Intact animals were served as control (Ctl. Animal model of left ventricular hypertrophy was induced by abdominal aortic banding. Serum catalase (CAT activity, malondialdehyde (MDA level and the activity of inhibition of free radicals DPPH were determined by the biochemical methods. Results: In Thy25+H and Thy50+H groups, the CAT activity was increased significantly in serum (p<0.01, vs. Ctl. Also, serum level of MDA was decreased significantly compared to the group H in Thy25+H and Thy50+H groups (p<0.05 and p<0.001, respectively. The effect of inhibiting DPPH free radicals was increased significantly in Thy25+H and Thy50+H groups compared to the group H (p<0.001 and p<0.05, respectively. Conclusion: The findings of this study suggest that thymol as an antioxidant causes cardioprotective effects and as well as prevents left ventricular hypertrophy via augmentation of serum antioxidant capacity.

Differential diagnosis of left ventricular hypertrophy: usefulness of multimodality imaging and tissue characterization with cardiac magnetic resonance.

Science.gov (United States)

Izgi, Cemil; Vassiliou, Vassilis; Baksi, A John; Prasad, Sanjay K

2016-11-01

Differential diagnosis of asymmetrical left ventricular hypertrophy may be challenging, particularly in patients with history of hypertension. A middle-aged man underwent an echocardiographic examination during workup for hypertension, which unexpectedly showed significant asymmetrical septal hypertrophy and raised suspicion for hypertrophic cardiomyopathy. Cardiovascular magnetic resonance confirmed the asymmetrical hypertrophy. No myocardial late gadolinium contrast enhancement was seen. However, precontrast T1 mapping revealed a low native myocardial T1 value. This was highly suggestive of Anderson-Fabry disease, which was subsequently proved with very low alpha galactosidase enzyme levels and mutation analysis. The case illustrates clinical usefulness of multimodality imaging and the novel tissue characterization techniques for assessment of left ventricular hypertrophy. © 2016, Wiley Periodicals, Inc.

Mouse models for the study of postnatal cardiac hypertrophy

Directory of Open Access Journals (Sweden)

A. Del Olmo-Turrubiarte

2015-06-01

Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

Three-dimensional CT might be a potential evaluation modality in correction of asymmetrical masseter muscle hypertrophy by botulinum toxin injection.

Science.gov (United States)

No, Yeon A; Ahn, Byeong Heon; Kim, Beom Joon; Kim, Myeung Nam; Hong, Chang Kwon

2016-01-01

For correction of this asymmetrical hypertrophy, botulinum toxin type A (BTxA) injection is one of convenient treatment modalities. Unfortunately, physical examination of masseter muscle is not enough to estimate the exact volume of muscle hypertrophy difference. Two Koreans, male and female, of bilateral masseter hypertrophy with asymmetricity were evaluated. BTxA (NABOTA(®), Daewoong, Co. Ltd., Seoul, Korea) was injected at master muscle site with total 50 U (25 U at each side) and volume change was evaluated with three-dimensional (3D) CT image analysis. Maximum reduction of masseter hypertrophy was recognized at 2-month follow-up and reduced muscle size started to restore after 3 months. Mean reduction of masseter muscle volume was 36% compared with baseline. More hypertrophied side of masseter muscle presented 42% of volume reduction at 2-month follow-up but less hypertrophied side of masseter muscle showed 30% of volume shrinkage. In conclusion, 3D CT image analysis might be the exact evaluation tool for correction of asymmetrical masseter hypertrophy by botulinum toxin injection.

Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs

Energy Technology Data Exchange (ETDEWEB)

Lundin, B.; Berntorp, E.; Pettersson, H.; Wirestam, R.; Jonsson, K.; Staahlberg, F.; Ljung, R. [Dept. of Radiology, Univ Hospital of Lund, Lund (Sweden)

2007-07-15

Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs.

Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs

International Nuclear Information System (INIS)

Lundin, B.; Berntorp, E.; Pettersson, H.; Wirestam, R.; Jonsson, K.; Staahlberg, F.; Ljung, R.

2007-01-01

Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs

Whey protein hydrolysate augments tendon and muscle hypertrophy independent of resistance exercise contraction mode

DEFF Research Database (Denmark)

Farup, Jean; Rahbek, S K; Vendelbo, M H

2014-01-01

In a comparative study, we investigated the effects of maximal eccentric or concentric resistance training combined with whey protein or placebo on muscle and tendon hypertrophy. 22 subjects were allocated into either a high-leucine whey protein hydrolysate + carbohydrate group (WHD) or a carbohy......In a comparative study, we investigated the effects of maximal eccentric or concentric resistance training combined with whey protein or placebo on muscle and tendon hypertrophy. 22 subjects were allocated into either a high-leucine whey protein hydrolysate + carbohydrate group (WHD...... or contraction mode effects. In conclusion, high-leucine whey protein hydrolysate augments muscle and tendon hypertrophy following 12 weeks of resistance training – irrespective of contraction mode....

Idiopathic masseter muscle hypertrophy.

Science.gov (United States)

Kebede, Biruktawit; Megersa, Shimalis

2011-11-01

Benign Masseteric Hypertrophy is a relatively uncommon condition that can occur unilaterally or bilaterally. Pain may be a symptom, but most frequently a clinician is consulted for cosmetic reasons. In some cases prominent Exostoses at the angle of the mandible are noted. Although it is tempting to point to Malocclusion, Bruxism, clenching, or Temporomandibular joint disorders, the etiology in the majority of cases is unclear. Diagnosis is based on awareness of the condition, clinical and radiographic findings, and exclusion of more serious Pathology such as Benign and Malignant Parotid Disease, Rhabdomyoma, and Lymphangioma. Treatment usually involves resection of a portion of the Masseter muscle with or without the underlying bone.

A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance.

Science.gov (United States)

Bosse, John D; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E Dale; Pereira, Troy J; Dolinsky, Vernon W; Symons, J David; Jalili, Thunder

2013-06-15

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature.

Macrophage microRNA-155 promotes cardiac hypertrophy and failure

NARCIS (Netherlands)

Heymans, Stephane; Corsten, Maarten F.; Verhesen, Wouter; Carai, Paolo; van Leeuwen, Rick E. W.; Custers, Kevin; Peters, Tim; Hazebroek, Mark; Stöger, Lauran; Wijnands, Erwin; Janssen, Ben J.; Creemers, Esther E.; Pinto, Yigal M.; Grimm, Dirk; Schürmann, Nina; Vigorito, Elena; Thum, Thomas; Stassen, Frank; Yin, Xiaoke; Mayr, Manuel; de Windt, Leon J.; Lutgens, Esther; Wouters, Kristiaan; de Winther, Menno P. J.; Zacchigna, Serena; Giacca, Mauro; van Bilsen, Marc; Papageorgiou, Anna-Pia; Schroen, Blanche

2013-01-01

Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this

Protection of MICU1 against myocardial hypertrophy induced by angiotensin Ⅱ

Directory of Open Access Journals (Sweden)

Yi YANG

2017-12-01

Full Text Available Objective To investigate the role of mitochondrial calcium uptake 1 (MICU1 in myocardial hypertrophy of mice and underlying mechanism. Methods The model of myocardial hypertrophy was established via incubation of mouse cardiac myocytes (MCM with 300nmol/L angiotensin Ⅱ (Ang Ⅱ for 48 hours in vitro. After that, MICU1 specific small interfering RNA (siRNA was delivered to knockdown MICU1 levels in MCM. On the other hand, adenovirus-mediated over-expression of MICU1 was transfected into MCM. Accordingly, the expressions of ANP and BNP in myocardial cells were measured by qRT- PCR. Mitochondrial membrane potential and ATP contents were detected by JC-1 assay kit and ATP assay kit, respectively. Then, Western blotting and qRT-PCR were used to detect the levels of MICU1 in myocardial cells. The mitochondrial Ca2+ contents were measured via atomic absorption flame spectroscopy. The size of myocardial cells was determined by α-actinin staining. Results Mitochondrial membrane potential and ATP contents in hypertrophic cardiomyocytes induced by AngⅡ were both decreased. Meanwhile, myocardial hypertrophy significantly increased mitochondrial Ca2+ contents but decreased MICU1 levels. With the method of genetic intervention, we found that MICU1 deficiency exacerbated mitochondrial Ca2+ overload, increased cell surface and elevated the expression of BNP. Conversely, the overexpression of MICU1 obviously decreased mitochondrial Ca2+ overload, cell surface of MCM and expressions of ANP and BNP. Conclusion MICU1 alleviates AngⅡ-induced myocardial hypertrophy via inhibiting mitochondrial Ca2+ overload. DOI: 10.11855/j.issn.0577-7402.2017.12.05

Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

Science.gov (United States)

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

2008-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

Population-specific left ventricular hypertrophy in three groups from the northeastern region of India.

Science.gov (United States)

Borah, P K; Hazarika, N C; Biswas, D; Kalita, H C; Mahanta, J

2010-01-01

People living in the hills are continuously exposed to strenuous physical activity for their day-to-day work. Besides hypertension, left ventricular hypertrophy in different populations may be related to continuous physical activity. Electrocardiogram, blood pressure and sociodemographic information of 12 252 subjects > or = 30 years of age from three different population groups living in Mizoram (hilly) and Assam (plain) were recorded. Of them, 8058 were from Mizoram and 3180 and 1014 were Indigenous Assamese and tea garden workers of Assam. Among the subjects from Mizoram the percentage of smokers (41.9%), mean (SD) BMI (21.9 [3.8]) and waist-hip ratio (0.87 [0.02]) were significantly higher than in those from other groups. Tea garden workers had a higher mean systolic blood pressure (145.2 [25.7]) and diastolic blood pressure (87.6 [13.6]). The prevalence of left ventricular hypertrophy was highest among tea garden workers (16.5%) followed by people from Mizoram (3.7%) and the indigenous Assamese (2%) people. In spite of a significantly higher prevalence of hypertension among the indigenous Assamese community than among those from Mizoram, left ventricular hypertrophy was found to be lower in the former. High prevalence of left ventricular hypertrophy among tea garden workers was possibly related to a higher prevalence of hypertension but the higher prevalence of left ventricular hypertrophy among people from Mizoram might be related to more physical activity.

Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in Burmese python (Python bivittatus).

Science.gov (United States)

Slay, Christopher E; Enok, Sanne; Hicks, James W; Wang, Tobias

2014-05-15

Physiological cardiac hypertrophy is characterized by reversible enlargement of cardiomyocytes and changes in chamber architecture, which increase stroke volume and via augmented convective oxygen transport. Cardiac hypertrophy is known to occur in response to repeated elevations of O2 demand and/or reduced O2 supply in several species of vertebrate ectotherms, including postprandial Burmese pythons (Python bivittatus). Recent data suggest postprandial cardiac hypertrophy in P. bivittatus is a facultative rather than obligatory response to digestion, though the triggers of this response are unknown. Here, we hypothesized that an O2 supply-demand mismatch stimulates postprandial cardiac enlargement in Burmese pythons. To test this hypothesis, we rendered animals anemic prior to feeding, essentially halving blood oxygen content during the postprandial period. Fed anemic animals had heart rates 126% higher than those of fasted controls, which, coupled with a 71% increase in mean arterial pressure, suggests fed anemic animals were experiencing significantly elevated cardiac work. We found significant cardiac hypertrophy in fed anemic animals, which exhibited ventricles 39% larger than those of fasted controls and 28% larger than in fed controls. These findings support our hypothesis that those animals with a greater magnitude of O2 supply-demand mismatch exhibit the largest hearts. The 'low O2 signal' stimulating postprandial cardiac hypertrophy is likely mediated by elevated ventricular wall stress associated with postprandial hemodynamics. © 2014. Published by The Company of Biologists Ltd.

Apical hypertrophy associated with rapid T wave inversion on the electrocardiogram.

Science.gov (United States)

Yamanari, H; Saito, D; Mikio, K; Nakamura, K; Nanba, T; Morita, H; Mizuo, K; Sato, T; Ohe, T

1995-01-01

A 53-year-old man who had no chest pain and no family history of heart disease demonstrated a rapid T wave change on an electrocardiogram, from a positive T wave to a giant negative T wave, within 1 year. Echocardiography showed no left ventricular hypertrophy before or after the T wave change. Cine-magnetic resonance imaging revealed focal apical hypertrophy after the appearance of the giant negative T wave. Although T wave inversions sometimes develop within a short period in patients with hypertrophic cardiomyopathy, they are rare in a patient without hypertension or chest pain.

Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

Energy Technology Data Exchange (ETDEWEB)

Baptista, Ana, E-mail: baptista-ana@hotmail.com; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio [Centro Hospitalar de Trás-os-Montes e Alto Douro, Unidade de Vila Real (Portugal)

2015-08-15

Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m{sup 2} for women or ≥ 116 g/m{sup 2} for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m{sup 2} (± 28.5; 99.2 to 228.5 g/m{sup 2}] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

International Nuclear Information System (INIS)

Baptista, Ana; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio

2015-01-01

Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m 2 for women or ≥ 116 g/m 2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m 2 (± 28.5; 99.2 to 228.5 g/m 2 ] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

Directory of Open Access Journals (Sweden)

Yao Song

Full Text Available AIMS: It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo. METHODS AND RESULTS: We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis. CONCLUSION: CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.

Unilateral hypoplasia with contralateral hypertrophy of anterior belly of digastric muscle: a case report.

Science.gov (United States)

Ochoa-Escudero, Martin; Juliano, Amy F

2016-10-01

Anomalies of the anterior belly of the digastric muscle (DM) are uncommon. We present a case of hypoplasia of the anterior belly of the left DM with hypertrophy of the anterior belly of the contralateral DM. The importance of recognizing this finding is to differentiate hypoplasia of the anterior belly of the DM from denervation atrophy, and not to confuse contralateral hypertrophy with a submental mass or lymphadenopathy. In denervation atrophy of the anterior belly of the DM, associated atrophy of the ipsilateral mylohyoid muscle is present. Hypertrophy of the anterior belly of the contralateral DM can be differentiated from a submental mass or lymphadenopathy by recognizing its isodensity on computed tomography and isointensity on magnetic resonance imaging to other muscles, without abnormal contrast enhancement.

Sparing of the dystrophin-deficient cranial sartorius muscle is associated with classical and novel hypertrophy pathways in GRMD dogs.

Science.gov (United States)

Nghiem, Peter P; Hoffman, Eric P; Mittal, Priya; Brown, Kristy J; Schatzberg, Scott J; Ghimbovschi, Svetlana; Wang, Zuyi; Kornegay, Joe N

2013-11-01

Both Duchenne and golden retriever muscular dystrophy (GRMD) are caused by dystrophin deficiency. The Duchenne muscular dystrophy sartorius muscle and orthologous GRMD cranial sartorius (CS) are relatively spared/hypertrophied. We completed hierarchical clustering studies to define molecular mechanisms contributing to this differential involvement and their role in the GRMD phenotype. GRMD dogs with larger CS muscles had more severe deficits, suggesting that selective hypertrophy could be detrimental. Serial biopsies from the hypertrophied CS and other atrophied muscles were studied in a subset of these dogs. Myostatin showed an age-dependent decrease and an inverse correlation with the degree of GRMD CS hypertrophy. Regulators of myostatin at the protein (AKT1) and miRNA (miR-539 and miR-208b targeting myostatin mRNA) levels were altered in GRMD CS, consistent with down-regulation of myostatin signaling, CS hypertrophy, and functional rescue of this muscle. mRNA and proteomic profiling was used to identify additional candidate genes associated with CS hypertrophy. The top-ranked network included α-dystroglycan and like-acetylglucosaminyltransferase. Proteomics demonstrated increases in myotrophin and spectrin that could promote hypertrophy and cytoskeletal stability, respectively. Our results suggest that multiple pathways, including decreased myostatin and up-regulated miRNAs, α-dystroglycan/like-acetylglucosaminyltransferase, spectrin, and myotrophin, contribute to hypertrophy and functional sparing of the CS. These data also underscore the muscle-specific responses to dystrophin deficiency and the potential deleterious effects of differential muscle involvement. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway.

Science.gov (United States)

Su, Hongyan; Li, Jingyuan; Chen, Tongshuai; Li, Na; Xiao, Jie; Wang, Shujian; Guo, Xiaobin; Yang, Yi; Bu, Peili

2016-11-01

Melatonin is well known for its cardioprotective effects; however, whether melatonin exerts therapeutic effects on cardiomyocyte hypertrophy remains to be investigated, as do the mechanisms underlying these effects, if they exist. Cyclophilin A (CyPA) and its corresponding receptor, CD147, which exists in a variety of cells, play crucial roles in modulating reactive oxygen species (ROS) production. In this study, we explored the role of the CyPA/CD147 signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and the protective effects exerted by melatonin against Ang II-induced injury in cultured H9C2 cells. Cyclosporine A, a specific CyPA/CD147 signaling pathway inhibitor, was used to manipulate CyPA/CD147 activity. H9C2 cells were then subjected to Ang II or CyPA treatment in either the absence or presence of melatonin. Our results indicate that Ang II induces cardiomyocyte hypertrophy through the CyPA/CD147 signaling pathway and promotes ROS production, which can be blocked by melatonin pretreatment in a concentration-dependent manner, in cultured H9C2 cells and that CyPA/CD147 signaling pathway inhibition protects against Ang II-induced cardiomyocyte hypertrophy. The protective effects of melatonin against Ang II-induced cardiomyocyte hypertrophy depend at least partially on CyPA/CD147 inhibition.

Left ventricular hypertrophy among chronic kidney disease patients ...

African Journals Online (AJOL)

Introduction: The presence of left ventricular hypertrophy (LVH) in patients with Chronic Kidney Disease (CKD) is associated with worsening cardiovascular outcomes. There is a dearth of data on LVH in Ghanaian CKD patients. Methods: This was a cross sectional study carried out at the Komfo Anokye Teaching Hospital ...

Do stress fractures induce hypertrophy of the grafted fibula? A report of three cases received free vascularized fibular graft treatment for tibial defects.

Science.gov (United States)

Qi, Yong; Sun, Hong-Tao; Fan, Yue-Guang; Li, Fei-Meng; Lin, Zhou-Sheng

2016-06-01

The presence of large segmental defects of the diaphyseal bone is challenging for orthopedic surgeons. Free vascularized fibular grafting (FVFG) is considered to be a reliable reconstructive procedure. Stress fractures are a common complication following this surgery, and hypertrophy is the main physiological change of the grafted fibula. The exact mechanism of hypertrophy is not completely known. To the best of our knowledge, no studies have examined the possible relationship between stress fractures and hypertrophy. We herein report three cases of patients underwent FVFG. Two of them developed stress fractures and significant hypertrophy, while the remaining patient developed neither stress fractures nor significant hypertrophy. This phenomenon indicates that a relationship may exist between stress fractures and hypertrophy of the grafted fibula, specifically, that the presence of a stress fracture may initiate the process of hypertrophy.

Left-liver hypertrophy after therapeutic right-liver radioembolization is substantial but less than after portal vein embolization.

Science.gov (United States)

Garlipp, Benjamin; de Baere, Thierry; Damm, Robert; Irmscher, Romy; van Buskirk, Mark; Stübs, Patrick; Deschamps, Frederic; Meyer, Frank; Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Amthauer, Holger; Lippert, Hans; Ricke, Jens; Seidensticker, Max

2014-05-01

In patients with liver malignancies potentially amenable to curative extended right hepatectomy but insufficient size of the future liver remnant (FLR), portal vein embolization (PVE) of the tumor-bearing liver is used to induce contralateral liver hypertrophy but leaves the tumor untreated. Radioembolization (RE) treats the tumor in the embolized lobe along with contralateral hypertrophy induction. We performed a matched-pair analysis to compare the capacity for hypertrophy induction of these two modalities. Patients with right-hepatic secondary liver malignancies with no or negligible left-hepatic tumor involvement who were treated by right-lobar PVE (n = 141) or RE (n = 35) at two centers were matched for criteria known to influence liver regeneration following PVE: 1) baseline FLR/Total liver volume ratio (<25 versus ≥ 25%); 2) prior platinum-containing systemic chemotherapy; 3) embolization of segments 5-8 versus 4-8; and 4) baseline platelet count (<200 versus ≥ 200 Gpt/L).The primary endpoint was relative change in FLR volume from baseline to follow-up. Twenty-six matched pairs were identified. FLR volume increase from baseline to follow-up (median 33 [24-56] days after PVE or 46 [27-79] days after RE) was significant in both groups but PVE produced significantly more FLR hypertrophy than RE (61.5 versus 29%, P < 0.001). Time between treatment and follow-up was not correlated with the degree of contralateral hypertrophy achieved in both groups. Although group differences in patient history and treatment setting were present and some bias cannot be excluded, this was minimized by the matched-pair design, as remaining group differences after matching were found to have no significant influence on contralateral hypertrophy development. PVE induces significantly more contralateral hypertrophy than RE with therapeutic (nonlobectomy) doses. However, contralateral hypertrophy induced by RE is substantial and RE minimizes the risk of tumor progression in the

123I-MIBG myocardial imaging in hypertensive patients. Abnormality progresses with left ventricular hypertrophy

International Nuclear Information System (INIS)

Mitani, Isao; Sumita, Shinichi; Takahashi, Nobukazu; Ochiai, Hisao; Ishii, Masao

1996-01-01

Twenty-seven patients with essential hypertension were prospectively studied with 123 I-labeled metaiodobenzyl-guanidine ( 123 I-MIBG) to assess the presence and location of impaired sympathetic innervation in hypertrophied myocardium. Thirteen patients had left ventricular hypertrophy on echocardiography, and 14 had normal echocardiograms. The wash-out ratio of 123 I-MIBG in these two groups did not differ significantly (35.3±6.1 and 35.4±5.1) but was higher than in control subjects (29.4±6.7). The delayed heart-to-mediastinum count ratio was lower in the patients with hypertrophy than in the patients without hypertrophy (1.93±0.28 and 2.22±0.21; p<0.05) and the control subjects (1.93±0.28 and 2.33±0.25; p<0.05). On SPECT imaging, abnormalities in segmental uptake were frequent at the posterior and postero-lateral wall in both groups, although the hypertrophic group had more significant impairment. Our results lead to the hypothesis that hypertension in more advanced stages may be associated not only with hypertrophic changes but also with more advanced regional impairment of cardiac sympathetic innervation. (author)

Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.

Science.gov (United States)

Sevilla, María A; Voces, Felipe; Carrón, Rosalía; Guerrero, Estela I; Ardanaz, Noelia; San Román, Luis; Arévalo, Miguel A; Montero, María J

2004-07-02

Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal. Copyright 2004 Elsevier Inc.

Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

Science.gov (United States)

Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

2015-04-01

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

Cycle training induces muscle hypertrophy and strength gain: strategies and mechanisms.

Science.gov (United States)

Ozaki, Hayao; Loenneke, J P; Thiebaud, R S; Abe, T

2015-03-01

Cycle training is widely performed as a major part of any exercise program seeking to improve aerobic capacity and cardiovascular health. However, the effect of cycle training on muscle size and strength gain still requires further insight, even though it is known that professional cyclists display larger muscle size compared to controls. Therefore, the purpose of this review is to discuss the effects of cycle training on muscle size and strength of the lower extremity and the possible mechanisms for increasing muscle size with cycle training. It is plausible that cycle training requires a longer period to significantly increase muscle size compared to typical resistance training due to a much slower hypertrophy rate. Cycle training induces muscle hypertrophy similarly between young and older age groups, while strength gain seems to favor older adults, which suggests that the probability for improving in muscle quality appears to be higher in older adults compared to young adults. For young adults, higher-intensity intermittent cycling may be required to achieve strength gains. It also appears that muscle hypertrophy induced by cycle training results from the positive changes in muscle protein net balance.

Early decrease in dietary protein:energy ratio by fat addition and ontogenetic changes in muscle growth mechanisms of rainbow trout: short- and long-term effects.

Science.gov (United States)

Alami-Durante, Hélène; Cluzeaud, Marianne; Duval, Carine; Maunas, Patrick; Girod-David, Virginia; Médale, Françoise

2014-09-14

As the understanding of the nutritional regulation of muscle growth mechanisms in fish is fragmentary, the present study aimed to (1) characterise ontogenetic changes in muscle growth-related genes in parallel to changes in muscle cellularity; (2) determine whether an early decrease in dietary protein:energy ratio by fat addition affects the muscle growth mechanisms of rainbow trout (Oncorhynchus mykiss) alevins; and (3) determine whether this early feeding of a high-fat (HF) diet to alevins had a long-term effect on muscle growth processes in juveniles fed a commercial diet. Developmental regulation of hyperplasia and hypertrophy was evidenced at the molecular (expression of myogenic regulatory factors, proliferating cell nuclear antigen and myosin heavy chains (MHC)) and cellular (number and diameter of white muscle fibres) levels. An early decrease in dietary protein:energy ratio by fat addition stimulated the body growth of alevins but led to a fatty phenotype, with accumulation of lipids in the anterior part, and less caudal muscle when compared at similar body weights, due to a decrease in both the white muscle hyperplasia and maximum hypertrophy of white muscle fibres. These HF diet-induced cellular changes were preceded by a very rapid down-regulation of the expression of fast-MHC. The present study also demonstrated that early dietary composition had a long-term effect on the subsequent muscle growth processes of juveniles fed a commercial diet for 3 months. When compared at similar body weights, initially HF diet-fed juveniles indeed had a lower mean diameter of white muscle fibres, a smaller number of large white muscle fibres, and lower expression levels of MyoD1 and myogenin. These findings demonstrated the strong effect of early feed composition on the muscle growth mechanisms of trout alevins and juveniles.

Region specific patella tendon hypertrophy in humans following resistance training

DEFF Research Database (Denmark)

Kongsgaard, M.; Reitelseder, S; Pedersen, T.G.

2007-01-01

AIM: To examine if cross-sectional area (CSA) differs along the length of the human patellar tendon (PT), and if there is PT hypertrophy in response to resistance training. METHODS: Twelve healthy young men underwent baseline and post-training assessments. Maximal isometric knee extension strength...... (MVC) was determined unilaterally in both legs. PT CSA was measured at the proximal-, mid- and distal PT level and quadriceps muscle CSA was measured at mid-thigh level using magnetic resonance imaging. Mechanical properties of the patellar tendons were determined using ultrasonography. Subsequently....... CONCLUSIONS: To our knowledge, this study is the first to report tendon hypertrophy following resistance training. Further, the data show that the human PT CSA varies along the length of the tendon....

Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

Directory of Open Access Journals (Sweden)

Ana Baptista

2015-01-01

Full Text Available Abstract Background: Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. Objective: To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. Methods: The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. Results: A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%. Nine (19.1% showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5, a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. Conclusion: In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5.

Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models.

Science.gov (United States)

Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

2017-03-01

Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models

Energy Technology Data Exchange (ETDEWEB)

Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu [R& D, Safety Science Research, Kao Corporation, Tochigi (Japan); Yoshinari, Kouichi [Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan); Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp [R& D, Safety Science Research, Kao Corporation, Tochigi (Japan)

2017-03-01

Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. - Highlights: • Hypertrophy (H) and hypertrophic

Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models

International Nuclear Information System (INIS)

Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

2017-01-01

Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. - Highlights: • Hypertrophy (H) and hypertrophic

Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

Science.gov (United States)

Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

2017-03-01

The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2.

Science.gov (United States)

Witting, N; Duno, M; Vissing, J

2013-01-01

Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest that this unusual phenotype is caused by translation re-initiation downstream from the mutation site. Copyright © 2012 Elsevier B.V. All rights reserved.

N-terminal pro B-type natriuretic peptide predicts mortality in patients with left ventricular hypertrophy.

Science.gov (United States)

Garcia, Santiago; Akbar, Muhammad S; Ali, Syed S; Kamdar, Forum; Tsai, Michael Y; Duprez, Daniel A

2010-09-03

Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH. Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records. Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03). NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass. Copyright © 2009 Elsevier B.V. All rights reserved.

The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage.

Directory of Open Access Journals (Sweden)

Pingping Chen-An

Full Text Available Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants.Early chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13, by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers.Compared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05, of cartilage turnover (p<0.05, and of CTR (p<0.01. Salmon, but not human, calcitonin induced cAMP release (p<0.001. Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05.T3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects.

Vascular endothelial growth factor, capillarization, and function of the rat plantaris muscle at the onset of hypertrophy.

NARCIS (Netherlands)

Degens, H.; Moore, J.A.; Alway, S.E.

2003-01-01

Capillary proliferation occurs during compensatory hypertrophy. We investigated whether the expression of vascular endothelial growth factor (VEGF) is elevated at the onset of hypertrophy when capillary proliferation is minimal, and whether muscle damage as assessed by muscle force deficits, may

Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.

Science.gov (United States)

Liang, Lei; Shou, Xi-Ling; Zhao, Hai-Kang; Ren, Gu-Qun; Wang, Jian-Bang; Wang, Xi-Hui; Ai, Wen-Ting; Maris, Jackie R; Hueckstaedt, Lindsay K; Ma, Ai-Qun; Zhang, Yingmei

2015-02-01

Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial

Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men.

Science.gov (United States)

Mitchell, Cameron J; Churchward-Venne, Tyler A; Parise, Gianni; Bellamy, Leeann; Baker, Steven K; Smith, Kenneth; Atherton, Philip J; Phillips, Stuart M

2014-01-01

Muscle hypertrophy following resistance training (RT) involves activation of myofibrillar protein synthesis (MPS) to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE) in untrained men (n = 23) and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index  = 26.4±0.9 kg•m²) underwent a primed constant infusion of L-[ring-¹³C₆] phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (Pmuscle volume and acute rates of MPS measured over 1-3 h (r = 0.02), 3-6 h (r = 0.16) or the aggregate 1-6 h post-exercise period (r = 0.10). Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05) with phosphorylation of 4E-BP1(Thr37/46) at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.

Alternative fat sources to animal fat for pigs

DEFF Research Database (Denmark)

Lauridsen, Charlotte; Christensen, Thomas Bruun; Halekoh, Ulrich

2007-01-01

% of either animal fat, palm oil mix, palm oil, vegetable oil mix, coconut oil, or rapeseed oil were tested in weaned and growing pigs. It was concluded that several vegetable fat sources (palm oil mix, palm oil, coconut oil, rapeseed oil) could be used as alternatives to animal fat in pig feed, whereas fat......The use of fats and oils in diets for pigs is of great importance due to their high energy value. As a consequence of the BSE-crisis in the European Union, the amount of animal fat available for animal feeds has been reduced, and alternative fat sources are of increasing importance. In this paper...

Bilateral idiopathic calf muscle hypertrophy: an exceptional cause of unsightly leg curvature.

Science.gov (United States)

Herlin, C; Chaput, B; Rivier, F; Doucet, J C; Bigorre, M; Captier, G

2015-04-01

The authors present the management of a young female patient who presented with longstanding bilateral calf muscle hypertrophy, with no known cause. Taking into account the patient's wishes and the fact that the hypertrophy was mainly located in the posteromedial compartment, we chose to carry out a subtotal bilateral resection of medial gastrocnemius muscles. This procedure was performed with an harmonic scalpel, permitting a excellent cosmetic result while avoiding complications or functional impairment. After a reviewing of the commonly used techniques, the authors discuss the chosen surgical approach taking into account its clinical particularity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Factors influencing left ventricular hypertrophy in children and adolescents with or without family history of premature myocardial infarction

Directory of Open Access Journals (Sweden)

Seyyed Mohsen Hosseini

2014-01-01

Result : The results showed that among the studied variables, gender, age, body mass index, and blood pressure were associated with the left ventricular hypertrophy. Conclusion: Considering the results and previous studies in this field, it was observed that left ventricular hypertrophy exists at early ages, which is very dangerous and can lead to heart diseases at early ages. Factors such as being overweight, having high blood pressure, and being male cause left ventricular hypertrophy and lead to undiagnosable heart diseases.

Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

Directory of Open Access Journals (Sweden)

Mohammad T. Elnakish

2015-01-01

Full Text Available Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models.

Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

Directory of Open Access Journals (Sweden)

McIver Lauren J

2009-12-01

Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

A case report of cardia cancer complicated with idiopathic muscular hypertrophy of the oesophagus treated with thoracoscopic surgery.

Science.gov (United States)

Ren, Jun; Hao, Yingtao; Peng, Chuanliang

2018-01-01

The incidence of idiopathic muscular hypertrophy of oesophagus (IMHE) is low, and cancer with IMHE, showing significant hypertrophy of muscular layer of middle part of the oesophagus and successfully treated with minimally invasive thoracoscopic surgery.

Hearts from mice fed a non-obesogenic high-fat diet exhibit changes in their oxidative state, calcium and mitochondria in parallel with increased susceptibility to reperfusion injury.

Science.gov (United States)

Littlejohns, Ben; Pasdois, Philippe; Duggan, Simon; Bond, Andrew R; Heesom, Kate; Jackson, Christopher L; Angelini, Gianni D; Halestrap, Andrew P; Suleiman, M-Saadeh

2014-01-01

High-fat diet with obesity-associated co-morbidities triggers cardiac remodeling and renders the heart more vulnerable to ischemia/reperfusion injury. However, the effect of high-fat diet without obesity and associated co-morbidities is presently unknown. To characterize a non-obese mouse model of high-fat diet, assess the vulnerability of hearts to reperfusion injury and to investigate cardiac cellular remodeling in relation to the mechanism(s) underlying reperfusion injury. Feeding C57BL/6J male mice high-fat diet for 20 weeks did not induce obesity, diabetes, cardiac hypertrophy, cardiac dysfunction, atherosclerosis or cardiac apoptosis. However, isolated perfused hearts from mice fed high-fat diet were more vulnerable to reperfusion injury than those from mice fed normal diet. In isolated cardiomyocytes, high-fat diet was associated with higher diastolic intracellular Ca2+ concentration and greater damage to isolated cardiomyocytes following simulated ischemia/reperfusion. High-fat diet was also associated with changes in mitochondrial morphology and expression of some related proteins but not mitochondrial respiration or reactive oxygen species turnover rates. Proteomics, western blot and high-performance liquid chromatography techniques revealed that high-fat diet led to less cardiac oxidative stress, higher catalase expression and significant changes in expression of putative components of the mitochondrial permeability transition pore (mPTP). Inhibition of the mPTP conferred relatively more cardio-protection in the high-fat fed mice compared to normal diet. This study shows for the first time that high-fat diet, independent of obesity-induced co-morbidities, triggers changes in cardiac oxidative state, calcium handling and mitochondria which are likely to be responsible for increased vulnerability to cardiac insults.

Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

Directory of Open Access Journals (Sweden)

Aline Cristina Piratello

2010-01-01

Full Text Available OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated showed an increase on mean blood pressure compared with normotensive ones (controls and denervated. Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

Community level evaluation of adenoid hypertrophy on the basis of symptom scoring and its X-ray correlation

Directory of Open Access Journals (Sweden)

Yogita Dixit

2016-01-01

Full Text Available Introduction: One of the major causes of pediatric morbidity today at the community level is infection involving the ear, nose, and throat. Maximum of these patients respond well initially on general regular medications, but then recurrent complaints are not very uncommon. One of the major causes for such recurrence is hypertrophy of adenoids, the evaluation of which requires a battery of sophisticated investigative tools and expertise which are lacking at the community level. The aim of the study is to evaluate various symptoms related to adenoid hypertrophy and its correlation to the size of the adenoid seen in the lateral view nasopharyngeal X-ray. The aim of the study was to assess various symptoms related to adenoid hypertrophy and its correlation with the size of adenoid radiologically. Methods: A total of fifty cases of pediatric age with strong clinical suspicion of adenoid hypertrophy were included in the study. Through ENT examination was done. X-ray lateral view nasopharynx was obtained. Results: Adenoid hypertrophy was graded according to symptoms score and lateral cephalometric/radiographs. Snoring was the most frequent symptom which had a linear relation with the size of the adenoid. Conclusion: There was good agreement between symptom and the X-ray findings.

Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

Science.gov (United States)

Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

2015-09-01

The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

Science.gov (United States)

Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

2010-10-01

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

Differentiation of lard, chicken fat, beef fat and mutton fat by GCMS and EA-IRMS techniques.

Science.gov (United States)

Ahmad Nizar, Nina Naquiah; Nazrim Marikkar, Jalaldeen Mohamed; Hashim, Dzulkifly Mat

2013-01-01

A study was conducted to differentiate lard, chicken fat, beef fat and mutton fat using Gas Chromatography Mass Spectrometry (GC-MS) and Elemental Analyzer-Isotope Ratio Mass Spectrometry (EA-IRMS). The comparison of overall fatty acid data showed that lard and chicken fat share common characteristics by having palmitic, oleic and linoleic acid as major fatty acids while beef and mutton fats shared common characteristics by possessing palmitic, stearic and oleic acid as major fatty acids. The direct comparisons among the fatty acid data, therefore, may not be suitable for discrimination of different animal fats. When the fatty acid distributional data was subjected to Principle Component Analysis (PCA), it was demonstrated that stearic, oleic and linoleic acids as the most discriminating parameters in the clustering of animal fats into four subclasses. The bulk carbon analysis of animal fats using EA-IRMS showed that determination of the carbon isotope ratios (δ¹³C) would be a good indicator for discriminating lard, chicken fat, beef fat and mutton fat. This would lead to a faster and more efficient method to ascertain the source of origin of fats used in food products.

A clinical study of thallium-201 scintigraphy in hypertensive patients with and without left ventricular hypertrophy

International Nuclear Information System (INIS)

Ouyang Wei; He Guorong; Liu Jinhua; Huang Yuying; Qian Xuexian

2001-01-01

Objective: Based on coronary angiography, thallium-201 myocardial scintigraphy was evaluated in hypertensive patients with and without left ventricular hypertrophy, and the causes of its perfusion abnormalities were discussed. Methods: Thallium-201 myocardial scintigraphy was performed on 85 patients with clinically suspected coronary artery disease. Coronary angiography was performed on patients with perfusion abnormalities in one month after scintigraphy. Results: The rate of 201 Tl perfusion abnormalities in hypertensive patients with hypertrophy (85.7%) was higher than normal blood pressure (39.3%, P 201 Tl perfusion abnormalities occur in hypertensive patients with hypertrophy. The perfusion abnormalities may be caused not only by coronary large vessel disease, but also by coronary microvascular disease

SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

Directory of Open Access Journals (Sweden)

Tao Shen

2014-01-01

Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy.

Science.gov (United States)

Liu, Dan; Hu, Kai; Nordbeck, Peter; Ertl, Georg; Störk, Stefan; Weidemann, Frank

2016-05-10

Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.

Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy.

Science.gov (United States)

Galán, María; Varona, Saray; Guadall, Anna; Orriols, Mar; Navas, Miquel; Aguiló, Silvia; de Diego, Alicia; Navarro, María A; García-Dorado, David; Rodríguez-Sinovas, Antonio; Martínez-González, José; Rodriguez, Cristina

2017-09-01

Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H 2 O 2 production and with cardiofibroblast reprogramming. LOX overexpression promoted an age-associated concentric remodeling of the left ventricle and impaired diastolic function. Furthermore, LOX transgenesis aggravated angiotensin II (Ang II)-induced cardiac hypertrophy and dysfunction, which triggered a greater fibrotic response that was characterized by stronger collagen deposition and cross-linking and high expression of fibrotic markers. In addition, LOX transgenesis increased the Ang II-induced myocardial inflammatory infiltrate, exacerbated expression of proinflammatory markers, and decreased that of cardioprotective factors. Mechanistically, LOX overexpression enhanced oxidative stress and potentiated the Ang II-mediated cardiac activation of p38 MAPK while reducing AMPK activation. Our findings suggest that LOX induces an age-dependent disturbance of diastolic function and aggravates Ang II-induced hypertrophy, which provides novel insights into the role of LOX in cardiac performance.-Galán, M., Varona, S., Guadall, A., Orriols, M., Navas, M., Aguiló, S., de Diego, A., Navarro, M. A., García-Dorado, D., Rodríguez-Sinovas, A., Martínez-González, J., Rodriguez, C. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy. © FASEB.

Role of IGF-I in follistatin-induced skeletal muscle hypertrophy.

Science.gov (United States)

Barbé, Caroline; Kalista, Stéphanie; Loumaye, Audrey; Ritvos, Olli; Lause, Pascale; Ferracin, Benjamin; Thissen, Jean-Paul

2015-09-15

Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth. Copyright © 2015 the American Physiological Society.

The Relationship of Carotid Arterial Stiffness and Left Ventricular Concentric Hypertrophy in Hypertension.

Science.gov (United States)

Jaroch, Joanna; Łoboz-Grudzień, Krystyna; Magda, Stefania; Florescu, Maria; Bociąga, Zbigniew; Ciobanu, Andrea O; Kruszyńska, Ewa; Dudek, Krzysztof; Vinereanu, Dragos

2016-01-01

Left ventricular hypertrophy (LVH) and geometry patterns vary in different hemodynamic profiles The concentric hypertrophy (CH) pattern has been proved to have the worst prognosis. The aim of the study was to test the hypothesis that carotid artery stiffness, as a marker of vascular damage, is associated with CH, independently of other potential determinants such as demographic factors (age, sex, BMI), clinical parameters (smoking, diabetes, creatinine level) and hemodynamic variables (blood pressure, pulse pressure [PP]). The study involved 262 subjects (89 men): 202 patients with hypertension (153 untreated, 49 on medication), aged 55.7 ± 10 years, and 60 age-matched normal controls. The subjects were examined by echocardiography and carotid ultrasound with a high-resolution echo-tracking system. Based on the left ventricular mass index (LVMI) and relative wall thickness (RWT), the patients with hypertension were divided into four patterns of LVH and geometry: normal geometry (N, n = 57), concentric remodeling (CR, n = 48), concentric hypertrophy CH (n = 62) and eccentric hypertrophy (EH, n = 35). Intima-media thickness (IMT) and the parameters of arterial stiffness were also assessed using the β stiffness index (β), Young elastic modulus (Ep), arterial compliance (AC), one-point pulse wave velocity (PWVβ) and the wave reflection augmentation index (AI). Univariate analysis showed that the following variables are significant in determining CH: β > 8.4, Ep > 136 kPa, PWVβ > 7.1 m/s, AI > 21.9%, systolic BP > 151 mm Hg, PP > 54, IMT > 0.56 and the presence of diabetes. However, by multivariate analysis only AI (OR 3.65, p = 0.003), PWVβ > 7.1 m/s (OR 2.86, p = 0.014), systolic BP (OR 3.12, p = 0037) and the presence of diabetes (OR 3.75, p = 0.007) were associated independently with the occurrence of CH. Concentric hypertrophy in hypertension is strongly associated with carotid arterial stiffness and wave reflection parameters, independently of the influence

Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

African Journals Online (AJOL)

Diabetes or hyperglycemia disrupts HIF-mediated cardiac hypertrophy adaptive regulatory mechanism [14]. In diabetic retinopathy, abnormal increase of ... detection system. Flow cytometry. After digesting with EDTA-free trypsin, the H9C2 cells were centrifuged at 1000 rpm for 5 min. After discarding the medium, the cells ...

Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage.

Science.gov (United States)

Damas, Felipe; Phillips, Stuart M; Libardi, Cleiton A; Vechin, Felipe C; Lixandrão, Manoel E; Jannig, Paulo R; Costa, Luiz A R; Bacurau, Aline V; Snijders, Tim; Parise, Gianni; Tricoli, Valmor; Roschel, Hamilton; Ugrinowitsch, Carlos

2016-09-15

Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes in myofibrillar protein synthesis (MyoPS) after an initial resistance exercise (RE) bout in the first week of RT (T1) were greater than those seen post-RE at the third (T2) and tenth week (T3) of RT, with values being similar at T2 and T3. Muscle damage (Z-band streaming) was the highest during post-RE recovery at T1, lower at T2 and minimal at T3. When muscle damage was the highest, so was the integrated MyoPS (at T1), but neither were related to hypertrophy; however, integrated MyoPS at T2 and T3 were correlated with hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent increases in MyoPS mainly after a progressive attenuation of muscle damage. Skeletal muscle hypertrophy is one of the main outcomes of resistance training (RT), but how hypertrophy is modulated and the mechanisms regulating it are still unknown. To investigate how muscle hypertrophy is modulated through RT, we measured day-to-day integrated myofibrillar protein synthesis (MyoPS) using deuterium oxide and assessed muscle damage at the beginning (T1), at 3 weeks (T2) and at 10 weeks of RT (T3). Ten young men (27 (1) years, mean (SEM)) had muscle biopsies (vastus lateralis) taken to measure integrated MyoPS and muscle damage (Z-band streaming and indirect parameters) before, and 24 h and 48 h post resistance exercise (post-RE) at T1, T2 and T3. Fibre cross-sectional area (fCSA) was evaluated using biopsies at T1, T2 and T3. Increases in fCSA were observed only at T3 (P = 0.017). Changes in MyoPS post-RE at T1, T2 and T3 were greater at T1 (P Muscle damage was the highest during post-RE recovery at T1, attenuated at T2 and further attenuated at T3. The change in MyoPS post-RE at both T2 and T3, but not at T1, was strongly correlated (r ≈ 0.9, P muscle hypertrophy. Initial Myo

Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in hypertrophy.

Directory of Open Access Journals (Sweden)

Ming Xu

2007-02-01

Full Text Available Pressure overload-induced hypertrophy is a key step leading to heart failure. The Ca(2+-induced Ca(2+ release (CICR process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca(2+ channel (LCC and ryanodine receptors (RyRs in aortic stenosis rat models of compensated (CHT and decompensated (DHT hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of "intermolecular failure." Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca(2+ release, visualized as "Ca(2+ spikes," became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca(2+ transients in CHT. These data suggested that, within a certain limit, termed the "stability margin," mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of "hidden" intermolecular failure in CHT has important clinical implications.

Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone.

Science.gov (United States)

Parr, Maria Kristina; Zhao, Piwen; Haupt, Oliver; Ngueu, Sandrine Tchoukouegno; Hengevoss, Jonas; Fritzemeier, Karl Heinrich; Piechotta, Marion; Schlörer, Nils; Muhn, Peter; Zheng, Wen-Ya; Xie, Ming-Yong; Diel, Patrick

2014-09-01

The phytoectysteroid ecdysterone (Ecdy) was reported to stimulate protein synthesis and enhance physical performance. The aim of this study was to investigate underlying molecular mechanisms particularly the role of ER beta (ERβ). In male rats, Ecdy treatment increased muscle fiber size, serum IGF-1 increased, and corticosteron and 17β-estradiol (E2) decreased. In differentiated C2C12 myoblastoma cells, treatment with Ecdy, dihydrotestosterone, IGF-1 but also E2 results in hypertrophy. Hypertrophy induced by E2 and Ecdy could be antagonized with an antiestrogen but not by an antiandrogen. In HEK293 cells transfected with ER alpha (ERα) or ERβ, Ecdy treatment transactivated a reporter gene. To elucidate the role of ERβ in Ecdy-mediated muscle hypertrophy, C2C12 myotubes were treated with ERα (ALPHA) and ERβ (BETA) selective ligands. Ecdy and BETA treatment but not ALPHA induced hypertrophy. The effect of Ecdy, E2, and BETA could be antagonized by an ERβ-selective antagonist (ANTIBETA). In summary, our results indicate that ERβ is involved in the mediation of the anabolic activity of the Ecdy. These findings provide new therapeutic perspectives for the treatment of muscle injuries, sarcopenia, and cachectic disease, but also imply that such a substance could be abused for doping purposes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

Science.gov (United States)

Marcotte, George R.; West, Daniel W.D.; Baar, Keith

2016-01-01

In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Lastly, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise. PMID:25359125

Pharmacological targeting of CDK9 in cardiac hypertrophy

Czech Academy of Sciences Publication Activity Database

Kryštof, Vladimír; Chamrád, Ivo; Jorda, Radek; Kohoutek, J.

2010-01-01

Roč. 30, č. 4 (2010), s. 646-666 ISSN 0198-6325 R&D Projects: GA ČR GA204/08/0511; GA ČR GA301/09/1832; GA ČR GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : P-TEFb * cardiac myocyte * cardiac hypertrophy Subject RIV: CE - Biochemistry Impact factor: 10.228, year: 2010

Radiofrequency Coblation Versus Intramural Bipolar Cautery for the Treatment of Inferior Turbinate Hypertrophy.

Science.gov (United States)

Shah, Anil N; Brewster, Douglas; Mitzen, Kelly; Mullin, David

2015-09-01

Compare intramural bipolar electrocautery and radiofrequency coblation in the treatment of inferior turbinate hypertrophy with regards to objective and subjective improvement in nasal obstruction, rate and type of complications, experience during the procedure, and rate of recovery. Prospective, single-blinded study. Single tertiary medical center from 2008 to 2010. Forty-one adult patients with inferior turbinate hypertrophy refractory to medical management were treated with radiofrequency coblation in one nostril and intramural bipolar cautery in the other. Subjective and objective data, including use of a Visual Analog Scale (VAS) for subjective outcomes, acoustic rhinometry, and nasal endoscopy, were then obtained from each patient comparing the 2 techniques. Radiofrequency coblation was significantly less painful than intramural bipolar cautery during the procedure (P = .03) and during the early postoperative period (P measured by acoustic rhinometry and subjective VAS outcomes. Radiofrequency coblation seems to offer an equivalent alternative to bipolar electrocautery for the treatment of inferior turbinate hypertrophy with less discomfort during the procedure and early post-operative period. © The Author(s) 2015.

Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.

Science.gov (United States)

Fan, Zhuo; Lv, Nanying; Luo, Xiao; Tan, Wen

2017-10-01

Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level. Copyright © 2017. Published by Elsevier B.V.

Four-group classification of left ventricular hypertrophy based on ventricular concentricity and dilatation identifies a low-risk subset of eccentric hypertrophy in hypertensive patients

DEFF Research Database (Denmark)

Bang, Casper N; Gerdts, Eva; Aurigemma, Gerard P

2014-01-01

BACKGROUND: Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end...

Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

International Nuclear Information System (INIS)

Kiso, Hironori; Ohba, Takayoshi; Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka; Murakami, Manabu; Ono, Kyoichi; Watanabe, Hiroyuki; Ito, Hiroshi

2013-01-01

Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression

Effect of Adenotonsillectomy on ADHD Symptoms of Children with Adenotonsillar Hypertrophy

Directory of Open Access Journals (Sweden)

Mohammad Hossein Dadgarnia

2012-08-01

Full Text Available Adenotonsillar hypertrophy and obstructive sleep disordered breathing can lead to attention deficit/hyperactivity disorder (ADHD. The purpose of this study was to evaluate effect of adenotonsillectomy on improvement of ADHD symptoms in a quasi-experimental (before and after study. The efficacy of adenotonsillectomy on improvement of ADHD symptoms of 35 children aged 5-12 years with adenotonsillar hypertrophy and ADHD was evaluated six months after surgery. Diagnosis of ADHD was based on the DSM-IV criteria in three subtypes (predominantly inattentive type, predominantly hyperactive-impulsive type and combined type. Seventeen boys (49% and eighteen girls (51% with mean (± SD age of 7.4 ± 3.8 years (range: 1-10 years were evaluated. Frequency of combined type of ADHD decreased significantly six months after adenotonsillectomy (54.3% versus 22.9%, P=0.003. ADHD inattention score (2.26 ± 1.93 versus 0.96 ± 0.45, P=0.005, hyperactivity score (4.23 ±3.57 versus 3.57 ±8, P=0.03 as well as ADHD combined score (9.66 ±2.58 versus 7.2 ±3.67, P=0.0001 improved significantly after surgery. Upper air way obstruction due to adenotonsillar hypertrophy might be an important and treatable cause of ADHD and should be considered in evaluation of affected children. Adenotonsillectomy in these children is associated with improvements in ADHD symptoms.

Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

NARCIS (Netherlands)

Hoffmann, S.; Krause, T.; van Geel, P. P.; Willenbrock, R.; Pagel, I.; Pinto, Y. M.; Buikema, H.; van Gilst, W. H.; Lindschau, C.; Paul, M.; Inagami, T.; Ganten, D.; Urata, H.

2001-01-01

Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT1 receptors. However, the role of myocardial AT1 receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

NARCIS (Netherlands)

Hoffmann, S; van Geel, PP; Willenbrock, R; Pagel, [No Value; Pinto, YM; Buikema, H; van Gilst, WH; Lindschau, C; Paul, M; Inagami, T; Ganten, D; Urata, H

2001-01-01

Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT(1) receptors. However, the role of myocardial AT(1) receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

Science.gov (United States)

Hossain, Ekhtear; Anand-Srivastava, Madhu B

2017-08-01

We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

Hypertension and left ventricular hypertrophy in liquidators of consequences of the Chernobyl nuclear accident

International Nuclear Information System (INIS)

Shal'nova, S.A.; Smolenskij, A.V.; Shamarin, V.M.; Ehktova, T.V.; Berzak, N.V.; Zemtsova, N.A.; Timofeeva, S.G.; Zhavoronkova, E.A.; Muromtseva, G.A.; Arkad'eva, M.A.; Deev, A.D.

1998-01-01

Echocardiography was used for the study of prevalence of left ventricular hypertrophy in 839 liquidators of consequences of the Chernobyl accident. Prevalence of left ventricular hypertrophy (left ventricular myocardial mass 134 g/m 2 ) was 10.3, 13.4 and 22.5 % in liquidators with normal blood pressure, borderline hypertension and hypertension, respectively. Liquidators with normal blood pressure had significantly greater left ventricular myocardial mass than normotensive men from general population while liquidators and non liquidators with hypertension had equal values of this parameter [ru

Incipient speciation driven by hypertrophied lips in Midas cichlid fishes?

Science.gov (United States)

Machado-Schiaffino, Gonzalo; Kautt, Andreas F; Torres-Dowdall, Julian; Baumgarten, Lukas; Henning, Frederico; Meyer, Axel

2017-04-01

Sympatric speciation has been debated in evolutionary biology for decades. Although it has gained in acceptance recently, still only a handful of empirical examples are seen as valid (e.g. crater lake cichlids). In this study, we disentangle the role of hypertrophied lips in the repeated adaptive radiations of Nicaraguan crater lake cichlid fish. We assessed the role of disruptive selection and assortative mating during the early stages of divergence and found a functional trade-off in feeding behaviour between thick- and thin-lipped ecotypes, suggesting that this trait is a target of disruptive selection. Thick-lipped fish perform better on nonevasive prey at the cost of a poorer performance on evasive prey. Using enclosures in the wild, we found that thick-lipped fish perform significantly better in rocky than in sandy habitats. We found almost no mixed pairs during two breeding seasons and hence significant assortative mating. Genetic differentiation between ecotypes seems to be related to the time since colonization, being subtle in L. Masaya (1600 generations ago) and absent in the younger L. Apoyeque (<600 generations ago). Genome-wide differentiation between ecotypes was higher in the old source lakes than in the young crater lakes. Our results suggest that hypertrophied lips might be promoting incipient sympatric speciation through divergent selection (ecological divergence in feeding performance) and nonrandom mating (assortative mating) in the young Nicaraguan crater lakes. Nonetheless, further manipulative experiments are needed in order to confirm the role of hypertrophied lips as the main cue for assortative mating. © 2017 John Wiley & Sons Ltd.

Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy.

Science.gov (United States)

Lee, Yun-Sil; Lehar, Adam; Sebald, Suzanne; Liu, Min; Swaggart, Kayleigh A; Talbot, C Conover; Pytel, Peter; Barton, Elisabeth R; McNally, Elizabeth M; Lee, Se-Jin

2015-10-15

Myostatin is a secreted signaling molecule that normally acts to limit muscle growth. As a result, there is extensive effort directed at developing drugs capable of targeting myostatin to treat patients with muscle loss. One potential concern with this therapeutic approach in patients with muscle degenerative diseases like muscular dystrophy is that inducing hypertrophy may increase stress on dystrophic fibers, thereby accelerating disease progression. To investigate this possibility, we examined the effect of blocking the myostatin pathway in dysferlin-deficient (Dysf(-/-)) mice, in which membrane repair is compromised, either by transgenic expression of follistatin in skeletal muscle or by systemic administration of the soluble form of the activin type IIB receptor (ACVR2B/Fc). Here, we show that myostatin inhibition by follistatin transgene expression in Dysf(-/-) mice results in early improvement in histopathology but ultimately exacerbates muscle degeneration; this effect was not observed in dystrophin-deficient (mdx) mice, suggesting that accelerated degeneration induced by follistatin transgene expression is specific to mice lacking dysferlin. Dysf(-/-) mice injected with ACVR2B/Fc showed significant increases in muscle mass and amelioration of fibrotic changes normally seen in 8-month-old Dysf(-/-) mice. Despite these potentially beneficial effects, ACVR2B/Fc treatment caused increases in serum CK levels in some Dysf(-/-) mice, indicating possible muscle damage induced by hypertrophy. These findings suggest that depending on the disease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which need to be weighed against the potential gains in muscle growth and decreased fibrosis. © The Author 2015. Published by Oxford University Press.

Pattern of left ventricular hypertrophy seen on transthoracic echo in patients with hypertensive cardiomyopathy when compared with idiopathic hypertrophic cardiomyopathy

International Nuclear Information System (INIS)

Mirza, S. J.; Radaideh, G. A.

2013-01-01

Objective: To explore the pattern of left ventricular hypertrophy caused by hypertension and to compare it with idiopathic hypertrophic cardiomyopathy. Methods: The retrospective study was conducted at the echocardiography lab of Rashid Hospital, Dubai, from January 2009 to January 2010. Cases of 11 patients with significant left ventricular hypertrophy (septum >15mm) due to underlying hypertension were analysed and compared with 11 cases of idiopathic hypertrophic cardiography (septum >15mm) to assess the two groups with similar baseline echocardiographic features. Minitab software was used for statistical analysis. Results: Although the pattern of hypertrophy in hypertensive patients was more concentric (n=5; 45%), there was also asymmetrical septal hypertrophy in 4 (36%) cases, particularly the elderly with sigmoid shape septum. There was evidence of resting mid-cavity gradient due to reduced left ventricular end-systolic diameter in 4 (36%) cases. Conclusion: Although the equation between hypertension and left ventricular hypertrophy is more concentric, but it can be associated with left ventricular outflow tract obstruction and significant mid-cavity gradients similar to that seen in idiopathic hypertrophic cardiomyopathy. (author)

beta-Adrenergic and cholinergic receptors in hypertension-induced hypertrophy

International Nuclear Information System (INIS)

Vatner, D.E.; Kirby, D.A.; Homcy, C.J.; Vatner, S.F.

1985-01-01

Perinephritic hypertension was produced in dogs by wrapping one kidney with silk and removing the contralateral kidney 1 week later. Mean arterial pressure rose from 104 +/- 3 to 156 +/- 11 mm Hg, while left ventricular free wall weight, normalized for body weight, was increased by 49%. Muscarinic, cholinergic receptor density measured with [ 3 H]-quinuclidinyl benzilate, fell in hypertensive left ventricles (181 +/- 19 fmol/mg, n = 6; p less than 0.01) as compared with that found in normal left ventricles (272 +/- 16 fmol/mg, n = 8), while receptor affinity was not changed. The beta-adrenergic receptor density, measured by binding studies with [ 3 H]-dihydroalprenolol, rose in the hypertensive left ventricles (108 +/- 10 fmol/mg, n = 7; p less than 0.01) as compared with that found in normal left ventricles (68.6 +/- 5.2 fmol/mg, n = 15), while beta-adrenergic receptor affinity decreased in the hypertensive left ventricles (10.4 +/- 1.2 nM) compared with that found in the normal left ventricles (5.0 +/- 0.7 nM). Plasma norepinephrine levels were similar in the two groups, but myocardial norepinephrine levels were depressed (p less than 0.05) in dogs with hypertension. Moderate left ventricular hypertrophy induced by long-term aortic banding in dogs resulted in elevations in beta-adrenergic receptor density (115 +/- 14 fmol/mg) and decreases in affinity (10.4 +/- 2.2 nM) similar to those observed in the dogs with left ventricular hypertrophy induced by hypertension. Thus, these results suggest that perinephritic hypertension in the dog induces divergent effects on cholinergic and beta-adrenergic receptor density. The increased beta-adrenergic receptor density and decreased affinity may be a characteristic of left ventricular hypertrophy rather than hypertension

Fatness

DEFF Research Database (Denmark)

Hansen, Anne Katrine Kleberg

In 1727, the English physician Thomas Short wrote: “I believe no Age did ever afford more instances of Corpulency than our own.” Even in the 18th century, fatness was addressed as an issue of special contemporary concern. This thesis probes concepts and perceptions of fatness in Western European...... Medicine c. 1700–1900. It has been written with particular attention to whether and how fatness has been regarded as a disease during that period in history. One purpose of the thesis is to investigate the immediate period before fatness allegedly became problematized. Another purpose has been to grasp...

Role of hypoxia-inducible factor in diabetic myocardial hypertrophy ...

African Journals Online (AJOL)

Purpose: This study was carried out to investigate the role of hypoxia-inducible factor (HIF) in diabetic cardiomyopathy in vitro. Methods: Hypoxia was induced chemically in H9C2 cells (cardiac hypertrophy model), and the cells were treated with phenylephrine (PE), deferoxamine (DFO), PE + DFO, and HIF-1α siRNA under ...

Buddleja officinalis Maximowicz extract inhibits lipid accumulation on adipocyte differentiation in 3T3-L1 cells and high-fat mice.

Science.gov (United States)

Roh, Changhyun; Park, Min-Kyoung; Shin, Hee-June; Jung, Uhee; Kim, Jin-Kyu

2012-07-23

Obesity is a global health problem. It is also known to be a risk factor for the development of metabolic disorders, type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we elucidated that Buddleja officinalis Maximowicz extract significantly inhibited lipid accumulation during 3T3-L1 adipocyte differentiation. Furthermore, Buddleja officinalis Maximowicz extract reduced the body weight gain induced through feeding a high-fat diet to C57BL/6 mice. The treatment of Buddleja officinalis Maximowicz extract significantly reduced the adipose tissue weight to 2.7/100 g of body weight in high-fat mice. When their adipose tissue morphology was investigated for histochemical staining, the distribution of cell size in the high-fat diet groups was hypertrophied compared with those from Buddleja officinalis Maximowicz extract-treated mice. In addition, in Buddleja officinalis Maximowicz extract-treated mice, a significant reduction of serum triglyceride and T-cholesterol was observed at to 21% and 17%, respectively. The discovery of bioactive compounds from diet or dietary supplementation is one of possible ways to control obesity and to prevent or reduce the risks of various obesity-related diseases. These results support that Buddleja officinalis Maximowicz extract is expected to create the therapeutic interest with respect to the treatment of obesity.

Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

Directory of Open Access Journals (Sweden)

Antônio Carlos Cicogna

1999-04-01

Full Text Available OBJECTIVE: To assess the effect of food restriction (FR on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR. METHODS: Isolated papillary muscle preparations of the left ventricle (LV of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1 reduction in the body weight and LV weight of SHR and WKY rats; 2 increase in the time to peak shortening and the time to peak developed tension (DT in the hypertrophied myocardium of the SHR; 3 diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy

Science.gov (United States)

Fry, Christopher S.; Lee, Jonah D.; Jackson, Janna R.; Kirby, Tyler J.; Stasko, Shawn A.; Liu, Honglu; Dupont-Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

2014-01-01

Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.—Fry, C. S., Lee, J. D., Jackson, J. R., Kirby, T. J., Stasko, S. A., Liu, H., Dupont-Versteegden, E. E., McCarthy, J. J., Peterson, C. A. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. PMID:24376025

Brain renin angiotensin system in cardiac hypertrophy and failure

Directory of Open Access Journals (Sweden)

Luciana eCampos

2012-01-01

Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

Science.gov (United States)

Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

2017-06-14

Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2 -knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2 -knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis -eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Effect of Berberine on PPARα/NO Activation in High Glucose- and Insulin-Induced Cardiomyocyte Hypertrophy

Directory of Open Access Journals (Sweden)

Mingfeng Wang

2013-01-01

Full Text Available Rhizoma coptidis, the root of Coptis chinensis Franch, has been used in China as a folk medicine in the treatment of diabetes for thousands of years. Berberine, one of the active ingredients of Rhizoma coptidis, has been reported to improve symptoms of diabetes and to treat experimental cardiac hypertrophy, respectively. The objective of this study was to evaluate the potential effect of berberine on cardiomyocyte hypertrophy in diabetes and its possible influence on peroxisome proliferator-activated receptor-α (PPARα/nitric oxide (NO signaling pathway. The cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L and insulin (0.1 μmol/L (HGI was characterized in rat primary cardiomyocyte by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expression were measured by western blot and real-time RT-PCR, respectively. The enzymatic activity of NO synthase (NOS was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. HGI significantly induced cardiomyocyte hypertrophy and decreased the expression of PPARα and endothelial NOS at the mRNA and protein levels, which occurred in parallel with declining NOS activity and NO concentration. The effect of HGI was inhibited by berberine (0.1 to 100 μmol/L, fenofibrate (0.3 μmol/L, or L-arginine (100 μmol/L. MK886 (0.3 μmol/L, a selective PPARα antagonist, could abolish the effects of berberine and fenofibrate. NG-nitro-L-arginine-methyl ester (100 μmol/L, a NOS inhibitor, could block the effects of L-arginine, but only partially blocked the effects of berberine. These results suggest that berberine can blunt HGI-induced cardiomyocyte hypertrophy in vitro, through the activation of the PPARα/NO signaling pathway.

Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure.

Directory of Open Access Journals (Sweden)

Fernanda P Prado

Full Text Available Hypertension causes cardiac hypertrophy, one of the most important risk factors for heart failure (HF. Despite the importance of cardiac hypertrophy as a risk factor for the development of HF, not all hypertrophied hearts will ultimately fail. Alterations of cytoskeletal and sarcolemma-associated proteins are considered markers cardiac remodeling during HF. Dystrophin provides mechanical stability to the plasma membrane through its interactions with the actin cytoskeleton and, indirectly, to extracellular matrix proteins. This study was undertaken to evaluate dystrophin and calpain-1 in the transition from compensated cardiac hypertrophy to HF. Wistar rats were subjected to abdominal aorta constriction and killed at 30, 60 and 90 days post surgery (dps. Cardiac function and blood pressure were evaluated. The hearts were collected and Western blotting and immunofluorescence performed for dystrophin, calpain-1, alpha-fodrin and calpastatin. Statistical analyses were performed and considered significant when p<0.05. After 90 dps, 70% of the animals showed hypertrophic hearts (HH and 30% hypertrophic+dilated hearts (HD. Systolic and diastolic functions were preserved at 30 and 60 dps, however, decreased in the HD group. Blood pressure, cardiomyocyte diameter and collagen content were increased at all time points. Dystrophin expression was lightly increased at 30 and 60 dps and HH group. HD group showed decreased expression of dystrophin and calpastatin and increased expression of calpain-1 and alpha-fodrin fragments. The first signals of dystrophin reduction were observed as early as 60 dps. In conclusion, some hearts present a distinct molecular pattern at an early stage of the disease; this pattern could provide an opportunity to identify these failure-prone hearts during the development of the cardiac disease. We showed that decreased expression of dystrophin and increased expression of calpains are coincident and could work as possible

Hypertrophied hearts: what of sevoflurane cardioprotection?

DEFF Research Database (Denmark)

Larsen, Jens Kjærgaard Rolighed; Smerup, Morten Holdgaard; Hasenkam, John Michael

2009-01-01

pigs (n=7-12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted......-at-risk) was reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). CONCLUSION: Sevoflurane abrogated...

Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy.

Science.gov (United States)

Kirby, Tyler J; Patel, Rooshil M; McClintock, Timothy S; Dupont-Versteegden, Esther E; Peterson, Charlotte A; McCarthy, John J

2016-03-01

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy. © 2016 Kirby et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy

International Nuclear Information System (INIS)

Shiba, Nobuyuki; Kagaya, Yutaka; Ishide, Nobumasa; Takeyama, Daiya; Yamane, Yuriko; Chida, Masanobu; Otani, Hiroki; Shirato, Kunio; Ido, Tatsuo.

1997-01-01

Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18 F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the interventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6±1.6 vs. 4.1±0.5, p<0.01) and posterolateral wall (5.9±0.7 vs. 3.8±0.5, p< 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases. (author)

The anti-inflammatory and antifibrotic effects of Coreopsis tinctoria Nutt on high-glucose-fat diet and streptozotocin-induced diabetic renal damage in rats.

Science.gov (United States)

Yao, Lan; Li, Linlin; Li, Xinxia; Li, Hui; Zhang, Yujie; Zhang, Rui; Wang, Jian; Mao, Xinmin

2015-09-07

Diabetic nephropathy is a serious complication of diabetes whose development process is associated with inflammation, renal hypertrophy, and fibrosis. Coreopsis tinctoria Nutt, traditionally used as a healthcare tea, has anti-inflammatory, anti-hyperlipidemia, and glycemic regulation activities. The aim of our study was to investigate the renal protective effect of ethyl acetate extract of C. tinctoria Nutt (AC) on high-glucose-fat diet and streptozotocin (STZ)-induced diabetic rats. A diabetic rat model was induced by high-glucose-fat diet and intraperitoneal injection of 35 mg/kg STZ. After treatment with AC at a daily dose of 150, 300 or, 600 mg/kg for 4 weeks, metabolic and renal function parameters of serum and urine were examined. Degree of renal damage, renal proinflammatory cytokines, and fibrotic protein expression were analyzed by histopathology and immunohistochemistry. Renal AMP-activated protein kinase (AMPK) and transforming growth factor (TGF)-β1/Smad signaling pathway were determined by western blotting. Diabetic rats showed obvious renal dysfunction, inflammation and fibrosis. However, AC significantly reduced levels of blood glucose, total cholesterol, triglyceride, blood urea nitrogen, serum creatinine and urinary albumin, as well as expression of kidney proinflammatory cytokines of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1. AC also ameliorated renal hypertrophy and fibrosis by reducing fibronectin and collagen IV and suppressing the TGF-β1/Smad signaling pathway. Meanwhile, AMPKα as a protective cytokine was markedly stimulated by AC. In summary, AC controls blood glucose, inhibits inflammatory and fibrotic processes, suppresses the TGF-β1/Smad signaling pathway, and activates phosphorylation of AMPKα in the kidneys, which confirms the protective effects of AC in the early stage of diabetic kidney disease.

Asymmetric septal hypertrophy of sporadic form with abnormal thallium perfusion and myocardial enzymes

International Nuclear Information System (INIS)

Nagata, Seiki; Minamikawa, Tetsuhiro; Park, Yung-Dae; Nishimura, Tsunehiko; Yutani, Chikao; Ohmori, Fumio; Sakakibara, Hiroshi; Nimura, Yasuharu

1986-01-01

Asymmetric septal hypertrophy with abnormal thallium scintigram and elevated cardiac enzymes were observed in five patients and were studied with special reference to the clinical significance of their clinicopathological features. They were not familial cardiomyopathy patients. Two of the five patients (Cases 1 and 2) exhibited the clinical features characteristic of hypertrophic cardiomyopathy without abnormal thallium perfusion and serum cardiac enzyme levels. A right endomyocardial biopsy for Case 1 disclosed myocardial fibrosis in addition to hypertrophy and disarray of myocardial fibers. The left ventricular cavities of two other patients (Cases 4 and 5) tended to be dilated with signs of impaired systolic function and asymmetric septal hypertrophy. A regional area of reduced thickness was observed in the medial portion of the left ventricular posterior wall of Case 4. The remaining case (Case 3) exhibited left ventricular dilatation and reduced left ventricular systolic function, disproportionate hypertrophy, and had clinical signs of congestive heart failure. Necropsy disclosed massive fibrosis and diffuse disarray of myocardial fibers. Some patients with familial hypertrophic cardiomyopathy progress to exhibit clinical features of dilated cardiomyopathy in the termimal stages, and have massive fibrosis of the myocardium histologically. Thallium scintigraphic abnormalities and elevated serum levels of cardiac enzymes, especially the LDH 1 isoenzyme, in patients with hypertrophic cardiomyopathy may be a meaningful indicator of such progression in its early stages. The five patients in the present study exhibited a variety of clinical and histological features which may comprise a spectrum of clinical conditions during the progression from hypertrophic cardiomyopathy to a condition like dilated cardiomyopathy, similar to that in familial patients. This progression and the factors promoting it should be studied further in the near future. (author)

Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload.

Science.gov (United States)

Kobara, Miyuki; Furumori-Yukiya, Akiko; Kitamura, Miho; Matsumura, Mihoko; Ohigashi, Makoto; Toba, Hiroe; Nakata, Tetsuo

2015-08-01

Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload-induced cardiac injury. Copyright © 2015 Elsevier Inc. All rights reserved.

S6K1 Is Required for Increasing Skeletal Muscle Force during Hypertrophy.

Science.gov (United States)

Marabita, Manuela; Baraldo, Martina; Solagna, Francesca; Ceelen, Judith Johanna Maria; Sartori, Roberta; Nolte, Hendrik; Nemazanyy, Ivan; Pyronnet, Stéphane; Kruger, Marcus; Pende, Mario; Blaauw, Bert

2016-10-04

Loss of skeletal muscle mass and force aggravates age-related sarcopenia and numerous pathologies, such as cancer and diabetes. The AKT-mTORC1 pathway plays a major role in stimulating adult muscle growth; however, the functional role of its downstream mediators in vivo is unknown. Here, we show that simultaneous inhibition of mTOR signaling to both S6K1 and 4E-BP1 is sufficient to reduce AKT-induced muscle growth and render it insensitive to the mTORC1-inhibitor rapamycin. Surprisingly, lack of mTOR signaling to 4E-BP1 only, or deletion of S6K1 alone, is not sufficient to reduce muscle hypertrophy or alter its sensitivity to rapamycin. However, we report that, while not required for muscle growth, S6K1 is essential for maintaining muscle structure and force production. Hypertrophy in the absence of S6K1 is characterized by compromised ribosome biogenesis and the formation of p62-positive protein aggregates. These findings identify S6K1 as a crucial player for maintaining muscle function during hypertrophy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation.

Science.gov (United States)

Chen, Fan; Chen, Dandan; Zhao, Xinmei; Yang, Shuai; Li, Zhe; Sanchis, Daniel; Jin, Liang; Qiang, Xizhe; Wang, Kaiye; Xu, Yitao; Zhang, Yubin; Ye, Junmei

2017-12-01

Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

NFKB activity decreased in BALB/c mice with high fat diet and fructose

Science.gov (United States)

Nur'aini, Farida Dewi; Rahayu, Sri; Rifa'i, Muhaimin

2017-05-01

Excessive consumption of fat and fructose leads to obesity due to lipid accumulation. The excessive lipid causes hypertrophy in the adipocytes which lead to cell death. Consequently, dead adipocytes will produce adipokines, which cause macrophages and lymphocytes to infiltrate into the adipose tissue, elevating pro-inflammatory cytokines, thus triggering the production of pro-inflammatory cytokines through NFκB activity. Elicited soybeans extract (ESE) with bacteria and light contain Glyceollin and Isoflavones, which inhibit the activation of NFKB and reduce plasma cholesterol levels by upregulating cholesterol metabolism. This study aimed to analyze the effect of ESE against the relative number of CD4+ NFκB+ cells in BALB/c mice spleen after administrated by high-fat diet food and fructose (HFD) for 20 weeks. Mice were given orally with ESE after administrated by HFD at dose 78 mg/kgBW (D1), 104 mg/kgBW (D2), and 130 mg/kgBW (D3) for 4 weeks. This study also used positive control (HFD mice model without ESE treatment) and normal mice. Identification of NFKB activation was conducted using Flowcytometry analytical methods. Our result indicated that ESE could decrease significantly activation of NFκB in CD4 cell compare than positive control. The optimum dose that can decrease the relative number of CD4+ NFκB+ cells is dose 3.

Intra-abdominal fat: Comparison of computed tomography fat ...

African Journals Online (AJOL)

Background: Intra-abdominal fat is an important factor in determining the metabolic syndrome/insulin resistance, and thus the risk of diabetes and ischaemic heart disease. Computed Tomography (CT) fat segmentation represents a defined method of quantifying intra-abdominal fat, with attendant radiation risks.

Exercise-Induced Muscle Damage and Hypertrophy: A Closer Look Reveals the Jury is Still Out

OpenAIRE

Schoenfeld, Brad; Contreras, Bret

2018-01-01

This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potenti...

Do metabolites that are produced during resistance exercise enhance muscle hypertrophy?

Science.gov (United States)

Dankel, Scott J; Mattocks, Kevin T; Jessee, Matthew B; Buckner, Samuel L; Mouser, J Grant; Loenneke, Jeremy P

2017-11-01

Many reviews conclude that metabolites play an important role with respect to muscle hypertrophy during resistance exercise, but their actual physiologic contribution remains unknown. Some have suggested that metabolites may work independently of muscle contraction, while others have suggested that metabolites may play a secondary role in their ability to augment muscle activation via inducing fatigue. Interestingly, the studies used as support for an anabolic role of metabolites use protocols that are not actually designed to test the importance of metabolites independent of muscle contraction. While there is some evidence in vitro that metabolites may induce muscle hypertrophy, the only study attempting to answer this question in humans found no added benefit of pooling metabolites within the muscle post-exercise. As load-induced muscle hypertrophy is thought to work via mechanotransduction (as opposed to being metabolically driven), it seems likely that metabolites simply augment muscle activation and cause the mechanotransduction cascade in a larger proportion of muscle fibers, thereby producing greater muscle growth. A sufficient time under tension also appears necessary, as measurable muscle growth is not observed after repeated maximal testing. Based on current evidence, it is our opinion that metabolites produced during resistance exercise do not have anabolic properties per se, but may be anabolic in their ability to augment muscle activation. Future studies are needed to compare protocols which produce similar levels of muscle activation, but differ in the magnitude of metabolites produced, or duration in which the exercised muscles are exposed to metabolites.

Accessory papillary muscles and papillary muscle hypertrophy are associated with sudden cardiac arrest of unknown cause.

Science.gov (United States)

Uhm, Jae-Sun; Youn, Jong-Chan; Lee, Hye-Jeong; Park, Junbeom; Park, Jin-Kyu; Shim, Chi Young; Hong, Geu-Ru; Joung, Boyoung; Pak, Hui-Nam; Lee, Moon-Hyoung

2015-10-15

The present study was performed for elucidating the associations between the morphology of the papillary muscles (PMs) and sudden cardiac arrest (SCA). We retrospectively reviewed history, laboratory data, electrocardiography, echocardiography, coronary angiography, and cardiac CT/MRI for 190 patients with SCA. The prevalence of accessory PMs and PM hypertrophy in patients with SCA of unknown cause was compared with that in patients with SCA of known causes and 98 age- and sex-matched patients without SCA. An accessory PM was defined as a PM with origins separated from the anterolateral and posteromedial PMs, or a PM that branched into two or three bellies at the base of the anterolateral or posteromedial PM. PM hypertrophy was defined as at least one of the two PMs having a diameter of ≥1.1cm. In 49 patients (age 49.9±15.9years; 38 men) the cause of SCA was unknown, whereas 141 (age 54.2±16.6years; 121 men) had a known cause. The prevalence of accessory PMs was significantly higher in the unknown-cause group than in the known-cause group (24.5% and 7.8%, respectively; p=0.002) or the no-SCA group (7.1%, p=0.003). The same was true for PM hypertrophy (unknown-cause 12.2%, known-cause 2.1%, p=0.010; no SCA group 1.0%, p=0.006). By logistic regression, accessory PM and PM hypertrophy were independently associated with sudden cardiac arrest of unknown cause. An accessory PM and PM hypertrophy are associated with SCA of unknown cause. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

Science.gov (United States)

Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

1997-08-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

Galectin-3 levels relate in children to total body fat, abdominal fat, body fat distribution, and cardiac size.

Science.gov (United States)

Dencker, Magnus; Arvidsson, Daniel; Karlsson, Magnus K; Wollmer, Per; Andersen, Lars B; Thorsson, Ola

2018-03-01

Galectin-3 has recently been proposed as a novel biomarker for cardiovascular disease in adults. The purpose of this investigation was to assess relationships between galectin-3 levels and total body fat, abdominal fat, body fat distribution, aerobic fitness, blood pressure, left ventricular mass, left atrial size, and increase in body fat over a 2-year period in a population-based sample of children. Our study included 170 children aged 8-11 years. Total fat mass and abdominal fat were measured by dual-energy x-ray absorptiometry (DXA). Body fat distribution was expressed as abdominal fat/total fat mass. Maximal oxygen uptake was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure and pulse pressure were measured. Left atrial size, left ventricular mass, and relative wall thickness were measured by echocardiography. Frozen serum samples were analyzed for galectin-3 by the Proximity Extension Assay technique. A follow-up DXA scan was performed in 152 children 2 years after the baseline exam. Partial correlations, with adjustment for sex and age, between galectin-3 versus body fat measurements indicated weak to moderate relationships. Moreover, left atrial size, left ventricular mass, and relative wall thickness and pulse pressure were also correlated with galectin-3. Neither systolic blood pressure nor maximal oxygen uptake was correlated with galectin-3. There was also a correlation between galectin-3 and increase in total body fat over 2 years, while no such correlations were found for the other fat measurements. More body fat and abdominal fat, more abdominal body fat distribution, more left ventricular mass, and increased left atrial size were all associated with higher levels of galectin-3. Increase in total body fat over 2 years was also associated with higher levels of galectin-3. What is Known: • Galectin-3 has been linked to obesity and been proposed to be a novel biomarker

Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy.

Science.gov (United States)

Reza, Musarrat Maisha; Subramaniyam, Nathiya; Sim, Chu Ming; Ge, Xiaojia; Sathiakumar, Durgalakshmi; McFarlane, Craig; Sharma, Mridula; Kambadur, Ravi

2017-10-24

Exercise induces expression of the myokine irisin, which is known to promote browning of white adipose tissue and has been shown to mediate beneficial effects following exercise. Here we show that irisin induces expression of a number of pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic differentiation and myoblast fusion via activation of IL6 signaling. Injection of irisin in mice induces significant hypertrophy and enhances grip strength of uninjured muscle. Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis. In addition, irisin injection rescues loss of skeletal muscle mass following denervation by enhancing satellite cell activation and reducing protein degradation. These data suggest that irisin functions as a pro-myogenic factor in mice.

Molecular and cellular characterization of cardiac overload-induced hypertrophy and failure

NARCIS (Netherlands)

Umar, Soban

2009-01-01

In neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects of phenylephrine (chapter 2). Ventricular failure is associated with disturbed collagen turnover.

Fat Quality Influences the Obesogenic Effect of High Fat Diets

Directory of Open Access Journals (Sweden)

Raffaella Crescenzo

2015-11-01

Full Text Available High fat and/or carbohydrate intake are associated with an elevated risk for obesity and chronic diseases such as diabetes and cardiovascular diseases. The harmful effects of a high fat diet could be different, depending on dietary fat quality. In fact, high fat diets rich in unsaturated fatty acids are considered less deleterious for human health than those rich in saturated fat. In our previous studies, we have shown that rats fed a high fat diet developed obesity and exhibited a decrease in oxidative capacity and an increase in oxidative stress in liver mitochondria. To investigate whether polyunsaturated fats could attenuate the above deleterious effects of high fat diets, energy balance and body composition were assessed after two weeks in rats fed isocaloric amounts of a high-fat diet (58.2% by energy rich either in lard or safflower/linseed oil. Hepatic functionality, plasma parameters, and oxidative status were also measured. The results show that feeding on safflower/linseed oil diet attenuates the obesogenic effect of high fat diets and ameliorates the blood lipid profile. Conversely, hepatic steatosis and mitochondrial oxidative stress appear to be negatively affected by a diet rich in unsaturated fatty acids.

Exercise quantity-dependent muscle hypertrophy in adult zebrafish (Danio rerio).

Science.gov (United States)

Hasumura, Takahiro; Meguro, Shinichi

2016-07-01

Exercise is very important for maintaining and increasing skeletal muscle mass, and is particularly important to prevent and care for sarcopenia and muscle disuse atrophy. However, the dose-response relationship between exercise quantity, duration/day, and overall duration and muscle mass is poorly understood. Therefore, we investigated the effect of exercise duration on skeletal muscle to reveal the relationship between exercise quantity and muscle hypertrophy in zebrafish forced to exercise. Adult male zebrafish were exercised 6 h/day for 4 weeks, 6 h/day for 2 weeks, or 3 h/day for 2 weeks. Flow velocity was adjusted to maximum velocity during continual swimming (initial 43 cm/s). High-speed consecutive photographs revealed that zebrafish mainly drove the caudal part. Additionally, X-ray micro computed tomography measurements indicated muscle hypertrophy of the mid-caudal half compared with the mid-cranial half part. The cross-sectional analysis of the mid-caudal half muscle revealed that skeletal muscle (red, white, or total) mass increased with increasing exercise quantity, whereas that of white muscle and total muscle increased only under the maximum exercise load condition of 6 h/day for 4 weeks. Additionally, the muscle fiver size distributions of exercised fish were larger than those from non-exercised fish. We revealed that exercise quantity, duration/day, and overall duration were correlated with skeletal muscle hypertrophy. The forced exercise model enabled us to investigate the relationship between exercise quantity and skeletal muscle mass. These results open up the possibility for further investigations on the effects of exercise on skeletal muscle in adult zebrafish.

Role of heterotrimeric G protein and calcium in cardiomyocyte hypertrophy induced by IGF-1.

Science.gov (United States)

Carrasco, Loreto; Cea, Paola; Rocco, Paola; Peña-Oyarzún, Daniel; Rivera-Mejias, Pablo; Sotomayor-Flores, Cristian; Quiroga, Clara; Criollo, Alfredo; Ibarra, Cristian; Chiong, Mario; Lavandero, Sergio

2014-04-01

In the heart, insulin-like growth factor-1 (IGF-1) is a peptide with pro-hypertrophic and anti-apoptotic actions. The pro-hypertrophic properties of IGF-1 have been attributed to the extracellular regulated kinase (ERK) pathway. Recently, we reported that IGF-1 also increases intracellular Ca(2+) levels through a pertussis toxin (PTX)-sensitive G protein. Here we investigate whether this Ca(2+) signal is involved in IGF-1-induced cardiomyocyte hypertrophy. Our results show that the IGF-1-induced increase in Ca(2+) level is abolished by the IGF-1 receptor tyrosine kinase inhibitor AG538, PTX and the peptide inhibitor of Gβγ signaling, βARKct. Increases in the activities of Ca(2+) -dependent enzymes calcineurin, calmodulin kinase II (CaMKII), and protein kinase Cα (PKCα) were observed at 5 min after IGF-1 exposure. AG538, PTX, βARKct, and the dominant negative PKCα prevented the IGF-1-dependent phosphorylation of ERK1/2. Participation of calcineurin and CaMKII in ERK phosphorylation was discounted. IGF-1-induced cardiomyocyte hypertrophy, determined by cell size and β-myosin heavy chain (β-MHC), was prevented by AG538, PTX, βARKct, dominant negative PKCα, and the MEK1/2 inhibitor PD98059. Inhibition of calcineurin with CAIN did not abolish IGF-1-induced cardiac hypertrophy. We conclude that IGF-1 induces hypertrophy in cultured cardiomyocytes by activation of the receptor tyrosine kinase activity/βγ-subunits of a PTX-sensitive G protein/Ca(2+) /PKCα/ERK pathway without the participation of calcineurin. © 2013 Wiley Periodicals, Inc.

Effect of graded levels of rapeseed oil in isonitrogenous diets on the development of the gastrointestinal tract, and utilisation of protein, fat and energy in broiler chickens

DEFF Research Database (Denmark)

Jørgensen, Henry; Zhao, Xin Quan; Theil, Peter Kappel

2008-01-01

The effect of feeding 0, 4, 8 and 16% rapeseed oil from 12-42 days of age was studied in broiler chickens on performance, digestibility of nutrients, and development of gastrointestinal tract, protein and energy metabolism. Thirty six female chickens (Ross 208) with initial body weight average 246...... periods each of five days with two 24 h measurements of gas exchange in two open-air-circuit respiration chambers inserted on the second and third day of each period. The addition of rapeseed oil increased the amount of gutfill indicating a reduced rate of passage and causing a hypertrophy...... of the gastrointestinal tract. There was a positive effect on feed utilisation as well as on digestibility especially of dietary fat together with higher utilisation of protein with addition of rapeseed oil. The partial fat digestibility of rapeseed oil estimated by regression was 91.1% and the partial metabolisability...

Serum uric acid is associated with left ventricular hypertrophy independent of serum parathyroid hormone in male cardiac patients.

Directory of Open Access Journals (Sweden)

Shu-ichi Fujita

Full Text Available BACKGROUND: Several studies have shown that serum uric acid (UA is associated with left ventricular (LV hypertrophy. Serum levels of parathyroid hormone (PTH, which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown. PURPOSE: We investigated whether the relationship between serum uric acid (UA and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients. METHODS AND RESULTS: In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65 ± 12 years who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R = 0.34, P<0.001 but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48-5.28, P = 0.002 per one standard deviation increase. CONCLUSIONS: Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.

Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men.

Directory of Open Access Journals (Sweden)

Cameron J Mitchell

Full Text Available Muscle hypertrophy following resistance training (RT involves activation of myofibrillar protein synthesis (MPS to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE in untrained men (n = 23 and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index  = 26.4±0.9 kg•m² underwent a primed constant infusion of L-[ring-¹³C₆] phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (P<0.001 above rest 60-180 min post-exercise and 184±28% (P = 0.037 180-360 min post exercise. Quadriceps volume increased 7.9±1.6% (-1.9-24.7% (P<0.001 after training. There was no correlation between changes in quadriceps muscle volume and acute rates of MPS measured over 1-3 h (r = 0.02, 3-6 h (r = 0.16 or the aggregate 1-6 h post-exercise period (r = 0.10. Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05 with phosphorylation of 4E-BP1(Thr37/46 at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.

Visualization of hypertrophied papillary muscle mimicking left ventricular mass on gated blood pool and T1-201 myocardial perfusion imaging

International Nuclear Information System (INIS)

Bunko, H.; Nakajima, K.; Tonami, N.; Asanoi, H.; Hisada, K.

1981-01-01

A sixty-year old man with acute myocardial infarction was incidentally found to have a hypertrophied anterolateral papillary muscle (ALPPM) of the left ventricle on gated blood pool (GBP) and T1-201 myocardial perfusion images. Hypertrophy of the ALPPM was visualized as a movable defect in the lateral basal area on GBP imaging throughout the cardiac cycle and on the TI-201 study as a radionuclide accumulating structure, consistent with the defect in the GBP. A combination of these findings may suggest the presence of a hypertrophied papillary muscle of the left ventricle

Premature osteoarthritis of the knee associated with cartilage hypertrophy and phalangeal dysgenesis

International Nuclear Information System (INIS)

Vital, E.M.J.; Hutton, C.W.; Hughes, P.M.

2005-01-01

A woman presented with premature knee osteoarthritis associated with marked femoral cartilage hypertrophy. She also exhibited phalangeal dysgenesis, suggesting this may be an unrecognised syndrome that may predispose to knee osteoarthritis. (orig.)

Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

Science.gov (United States)

Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

2018-05-09

Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac

Focalized contractile impairment at hypertrophied myocardium proven in consideration of wall stress in patients with hypertrophic cardiomyopathy

International Nuclear Information System (INIS)

Yamazaki, Tadashi; Suzuki, Jun-ichi; Shimamoto, Ryoichi; Tsuji, Taeko; Ohmoto, Yuki; Toyo-oka, Teruhiko; Omata, Masao; Ohtomo, Kuni; Nagai, Ryozo

2006-01-01

In hypertrophic cardiomyopathy (HCM) a hyperkinetic state is sometimes observed in spite of impaired systolic function in the hypertrophied myocardium. The aim of the present study was to determine the mechanism of this paradox. Seventeen patients with HCM and 10 normal subjects underwent cine magnetic resonance (MR) imaging to measure percent systolic wall thickening and percent fractional shortening. The ratio of systolic radial wall stress of the LV at the hypertrophied myocardium over that at the nonhypertrophied myocardium was evaluated to describe the focal advantageous condition for wall thickening. The ratio was 0.66±0.36 at the start of contraction and 0.78±0.31 at early-systole, indicating consistently smaller radial wall stress at the hypertrophied myocardium. Although the condition for contraction was favorable (a ratio less than 1.00), percent systolic wall thickening at the hypertrophied myocardium (23.0±11.8%) was smaller than that at the nonhypertrophied myocardium (70.5±32.3%). Smaller end-diastolic dimension (HCM group; 45.2±4.2 mm, reference group; 48.9±4.1 mm, P=0.04) with a statistically identical value of systolic decrease in intraventricular dimension (HCM group; 19.7±3.9 mm, reference group; 18.9±3.2 mm, P=0.60) yielded high percent fractional shortening in patients with HCM (43.5±7.6%). Although contractile impairment was proven at the hypertrophied region with low radial wall stress in the HCM group, the smaller end-diastolic dimension in this group resulted in high percent fractional shortening. (author)

Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

Science.gov (United States)

Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

2017-06-01

Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Hipertrofia benigna do músculo masseter Benign masseter muscle hypertrophy

Directory of Open Access Journals (Sweden)

Daniel Zeni Rispoli

2008-10-01

Full Text Available A hipertrofia idiopática do músculo masseter (HIM é uma patologia pouco freqüente e de causa desconhecida. Alguns autores correlacionam tal condição com hábitos de mascar gomas, disfunção da articulação temporomandibular (ATM, hipertrofias congênitas e funcionais, e distúrbios emocionais (nervosismo e ansiedade. A maioria dos pacientes queixa-se da alteração estética decorrente da assimetria facial, também chamada "face quadrada", no entanto, sintomas como trismo, protrusão e bruxismo também podem ocorrer. Os objetivos deste estudo foram: relatar um caso de HIM e descrever a sintomatologia e o tratamento realizado. O paciente relatava aumento bilateral na região do ângulo da mandíbula de evolução lenta e progressiva. Negava dor ou desconforto, porém se queixava de otalgia bilateral, trismo noturno e ansiedade. Ao exame físico, observou-se hipertrofia bilateral de masseter sem alterações inflamatórias no local. Foi indicado tratamento cirúrgico com abordagem extra-oral. Exames complementares são indicados na dúvida diagnóstica. A conduta terapêutica varia de conservadora a cirúrgica, sendo que esta depende principalmente da experiência e da habilidade do cirurgião.Idiopathic hypertrophy of the masseter muscle is a rare disorder of unknown cause. Some authors associate it with the habit of chewing gum, temporo-mandibular joint disorder, congenital and functional hypertrophies, and emotional disorders (stress and nervousness. Most patients complain of the cosmetic change caused by facial asymmetry, also called square face, however, symptoms such as trismus, protrusion and bruxism may also occur. The goals of the present investigation were: to report a case of idiopathic masseter hypertrophy, describe its symptoms and treatment. The patient reported bilateral bulging in the region of the mandible angle, of slow and progressive evolution. He did not complain of pain or discomfort, however there was bilateral

UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

Directory of Open Access Journals (Sweden)

Hongmei Lang

2018-04-01

Full Text Available Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3 plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5% or a high-salt (HS, 8% diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

Dance band on the Titanic: biomechanical signaling in cardiac hypertrophy.

Science.gov (United States)

Sussman, Mark A; McCulloch, Andrew; Borg, Thomas K

2002-11-15

Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.

Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

International Nuclear Information System (INIS)

Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

2005-01-01

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

Possibility of leg muscle hypertrophy by ambulation in older adults: a brief review

Directory of Open Access Journals (Sweden)

Ozaki H

2013-03-01

Full Text Available Hayao Ozaki,1 Jeremy P Loenneke,2 Robert S Thiebaud,2 Joel M Stager,3 Takashi Abe31Juntendo University, Inzai, Chiba, Japan; 2Department of Health and Exercise Science, University of Oklahoma, Norman, OK, USA; 3Department of Kinesiology, Indiana University, Bloomington, IN, USAAbstract: It is known that ambulatory exercises such as brisk walking and jogging are potent stimuli for improving aerobic capacity, but it is less understood whether ambulatory exercise can increase leg muscle size and function. The purpose of this brief review is to discuss whether or not ambulatory exercise elicits leg muscle hypertrophy in older adults. Daily ambulatory activity with moderate (>3 metabolic equivalents [METs], which is defined as the ratio of the work metabolic rate to the resting metabolic rate intensity estimated by accelerometer is positively correlated with lower body muscle size and function in older adults. Although there is conflicting data on the effects of short-term training, it is possible that relatively long periods of walking, jogging, or intermittent running for over half a year can increase leg muscle size among older adults. In addition, slow-walk training with a combination of leg muscle blood flow restriction elicits muscle hypertrophy only in the blood flow restricted leg muscles. Competitive marathon running and regular high intensity distance running in young and middle-aged adults may not produce leg muscle hypertrophy due to insufficient recovery from the damaging running bout, although there have been no studies that have investigated the effects of running on leg muscle morphology in older subjects. It is clear that skeletal muscle hypertrophy can occur independently of exercise mode and load.Keywords: aerobic exercise, muscle mass, aging, strength, sarcopenia

Effects of Resistance Training on Ventricular Function and Hypertrophy in a Rat Model

Science.gov (United States)

Barauna, Valério Garrone; Rosa, Kaleizu Teodoro; Irigoyen, Maria Cláudia; de Oliveira, Edilamar Menezes

2007-01-01

Objective: The purpose of this study was to follow the ventricular function and cardiac hypertrophy in rats undergoing a resistance-training program for a period of 3 months. Design: Forty animals were divided into two major groups: control (n=16) and resistance trained (n=24). From the resistance-trained group, 12 animals were resistance trained for 1 month and another 12 for 3 months. The resistance-training protocol was performed with 4 sets of 12 repetitions using 65% to 75% of one repetition maximum (maximum lifted weight with the exercise apparatus). Methods: Echocardiographic analysis was performed at the beginning of the resistance-training period and at the end of each month. The repetition maximum was measured every 2 weeks. Cardiac hypertrophy was determined by echocardiography, by the absolute weight of the cardiac chambers and by histology of the left ventricle. Results: Before resistance training, both groups had similar repetition maximums, ranging from 1.8-fold to 2-fold the body weight; however, at the end of the resistance-training period, the repetition maximum of the resistance-trained group was 6-fold greater than the body weight. The left ventricular mass as assessed by echocardiography was 8%, 12% and 16% larger in the resistance-trained group than in the control group in the first, second and third months, respectively. This hypertrophy showed a similar increase in the interventricular septum and in the free posterior wall mass. There was no reduction in the end-diastolic left ventricular internal diameter during the 3-month resistance-training period. Systolic function did not differ between the groups throughout the resistance-training period. Conclusion: Resistance training induces the development of concentric cardiac hypertrophy without ventricular dysfunction or cavity reduction. Although diastolic function was not completely investigated, we cannot exclude the possibility that resistance training results in diastolic dysfunction. PMID

Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

International Nuclear Information System (INIS)

Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

2008-01-01

Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1 , collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

Importance of Thrombocytes for the Hypertrophy Response after Portal Vein Embolization

NARCIS (Netherlands)

Sturesson, Christian; Hoekstra, Lisette; Andersson, Roland; van Gulik, Thomas M.

2015-01-01

Background/Aims: Thrombocytes have proved to be important for liver regeneration after liver resection in the experimental setting. The aim of our study is to examine the effects of thrombocytes on liver hypertrophy after portal vein embolization (PVE). Methodology: This retrospective cohort study

Temporalis muscle hypertrophy and reduced skull eccentricity in Duchenne muscular dystrophy.

Science.gov (United States)

Straathof, C S M; Doorenweerd, N; Wokke, B H A; Dumas, E M; van den Bergen, J C; van Buchem, M A; Hendriksen, J G M; Verschuuren, J J G M; Kan, H E

2014-10-01

Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship. © The Author(s) 2014.

Increased Adipocyte Size, Macrophage Infiltration, and Adverse Local Adipokine Profile in Perirenal Fat in Cushing's Syndrome.

Science.gov (United States)

Roerink, Sean H P P; Wagenmakers, Margreet A E M; Langenhuijsen, Johan F; Ballak, Dov B; Rooijackers, Hanne M M; d'Ancona, Frank C; van Dielen, François M; Smit, Jan W A; Plantinga, Theo S; Netea-Maier, Romana T; Hermus, Ad R M M

2017-08-01

To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushing's syndrome. Subcutaneous (SC) and perirenal (PR) adipose tissue of 10 patients with Cushing's syndrome was compared to adipose tissue of 10 gender-, age-, and BMI-matched controls with regard to adipocyte size determined by digital image analysis on hematoxylin and eosin stainings, macrophage infiltration determined by digital image analysis on CD68 stainings, and adipose tissue leptin and adiponectin levels using fluorescent bead immunoassays and ELISA techniques. Compared to the controls, mean adipocyte size was larger in PR adipose tissue in patients. The percentage of macrophage infiltration of the PR adipose tissue and PR adipose tissue lysate leptin levels were higher and adiponectin levels were lower in SC and PR adipose tissue lysates in patients. The adiponectin levels were also lower in the SC adipose tissue supernatants of patients. Associations were found between the severity of hypercortisolism and PR adipocyte size. Cushing's syndrome is associated with hypertrophy of PR adipocytes and a higher percentage of macrophage infiltration in PR adipose tissue. These changes are associated with an adverse local adipokine profile. © 2017 The Obesity Society.

[A swollen, painless calf caused by neurogenic muscle (pseudo)-hypertrophy

NARCIS (Netherlands)

Warrenburg, B.P.C. van de; Zwarts, M.J.; Engelen, B.G.M. van

2003-01-01

Neurogenic muscle (pseudo) hypertrophy of the calf was diagnosed in a 60-year-old man, who presented with chronic, painless and unilateral calf enlargement caused by a chronic S1 radiculopathy due to a lumbar disc hernia in the L5-S1 interspace. The differential diagnosis of a swelling of the calf

Skeletal muscle function and hypertrophy are diminished in old age.

NARCIS (Netherlands)

Degens, H.; Alway, S.E.

2003-01-01

Muscle loss occurs during aging. To investigate whether the hypertrophic response is attenuated at old age, we used male Fischer 344 (26 months old; n = 5) and Fischer 344 x Brown Norway rats (6, 9, and 33 months old; n = 8, 10, and 6, respectively). Hypertrophy of the left plantaris muscle was

The 4th Report of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy

DEFF Research Database (Denmark)

Bacharova, Ljuba; Estes, Harvey E; Schocken, Douglas D

2016-01-01

The 4th Report provides a brief review of publications focused on the electrocardiographic diagnosis of left ventricular hypertrophy published during the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis of Left Ventricular Hypertrophy. The Working Group recommended...... that ECG research and clinical attention be redirected from the estimation of LVM to the identification of electrical remodeling, to better understanding the sequence of events connecting electrical remodeling to outcomes. The need for a re-definition of terms and for a new paradigm is also stressed....

Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications.

Science.gov (United States)

Rader, Florian; Sachdev, Esha; Arsanjani, Reza; Siegel, Robert J

2015-04-01

Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis. Left ventricular hypertrophy develops in a sizeable proportion of patients before the onset of symptoms, and a growing body of literature demonstrates that regression of left ventricular hypertrophy resulting from aortic stenosis is incomplete after aortic valve replacement and associated with adverse early postoperative outcomes and worse long-term outcomes. Thus, reliance on the development of symptoms alone without consideration of structural abnormalities of the myocardium for optimal timing of aortic valve replacement potentially constitutes a missed opportunity to prevent postoperative morbidity and mortality from severe aortic stenosis, especially in the face of the quickly expanding indications of lower-risk transcatheter aortic valve replacement. The purpose of this review is to discuss the mechanisms and clinical implications of left ventricular hypertrophy in severe valvular aortic stenosis, which may eventually move to center stage as an indication for aortic valve replacement in the asymptomatic patient. Copyright © 2015 Elsevier Inc. All rights reserved.

Large asymmetric hypertrophy of rectus abdominis muscle in professional tennis players.

Directory of Open Access Journals (Sweden)

Joaquin Sanchis-Moysi

Full Text Available PURPOSE: To determine the volume and degree of asymmetry of the musculus rectus abdominis (RA in professional tennis players. METHODS: The volume of the RA was determined using magnetic resonance imaging (MRI in 8 professional male tennis players and 6 non-active male control subjects. RESULTS: Tennis players had 58% greater RA volume than controls (P = 0.01, due to hypertrophy of both the dominant (34% greater volume, P = 0.02 and non-dominant (82% greater volume, P = 0.01 sides, after accounting for age, the length of the RA muscle and body mass index (BMI as covariates. In tennis players, there was a marked asymmetry in the development of the RA, which volume was 35% greater in the non-dominant compared to the dominant side (P<0.001. In contrast, no side-to-side difference in RA volume was observed in the controls (P = 0.75. The degree of side-to-side asymmetry increased linearly from the first lumbar disc to the pubic symphysis (r = 0.97, P<0.001. CONCLUSIONS: Professional tennis is associated with marked hypertrophy of the musculus rectus abdominis, which achieves a volume that is 58% greater than in non-active controls. Rectus abdominis hypertrophy is more marked in the non-dominant than in the dominant side, particularly in the more distal regions. Our study supports the concept that humans can differentially recruit both rectus abdominis but also the upper and lower regions of each muscle. It remains to be determined if this disequilibrium raises the risk of injury.

Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

Science.gov (United States)

Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

2013-08-19

Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

Aldosterone Inhibits the Fetal Program and Increases Hypertrophy in the Heart of Hypertensive Mice

Science.gov (United States)

Azibani, Feriel; Devaux, Yvan; Coutance, Guillaume; Schlossarek, Saskia; Polidano, Evelyne; Fazal, Loubina; Merval, Regine; Carrier, Lucie; Solal, Alain Cohen; Chatziantoniou, Christos; Launay, Jean-Marie; Samuel, Jane-Lise; Delcayre, Claude

2012-01-01

Background Arterial hypertension (AH) induces cardiac hypertrophy and reactivation of “fetal” gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC) and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. Methodology/Principal Findings RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren) with cardiac hyperaldosteronism (AS mice) and systemic hypertension (Ren). AS-Ren mice had increased (x2) angiotensin II in plasma and increased (x2) aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70%) versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41%) in AS-Ren mice (P<0.05 vs Ren). The increase of ANP (x 2.5; P<0.01) mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (−75%, p<0.001) in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05), an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. Conclusions/Significance Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction of

Aldosterone inhibits the fetal program and increases hypertrophy in the heart of hypertensive mice.

Directory of Open Access Journals (Sweden)

Feriel Azibani

Full Text Available BACKGROUND: Arterial hypertension (AH induces cardiac hypertrophy and reactivation of "fetal" gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren with cardiac hyperaldosteronism (AS mice and systemic hypertension (Ren. AS-Ren mice had increased (x2 angiotensin II in plasma and increased (x2 aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70% versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41% in AS-Ren mice (P<0.05 vs Ren. The increase of ANP (x 2.5; P<0.01 mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (-75%, p<0.001 in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05, an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. CONCLUSIONS/SIGNIFICANCE: Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction

Study on thallium-201 myocardial perfusion scanning for detection of right ventricular hypertrophy in chronic pulmonary disease

International Nuclear Information System (INIS)

Kawai, Seiki

1980-01-01

Thallium-201 myocardial perfusion scanning was performed in 34 patients with chronic pulmonary disease for the purpose of detecting right ventricular hypertrophy. Thallium-201 activity ratio of left ventricle plus ventricular septum/right ventricle (TAR) was significantly correlated with hemodynamic findings such as pulmonary arterial mean pressure (r = -0.75, p 2 (p < 0.001). Assuming that TAR < 2 or TAR = 2 would indicate pulmonary hypertension, sensitivity was 95%, specificity 79%, validity score 75%, false positive 14% and false negative was 8%. TAR was compared with left to right ventricular mass ratio using Fulton's method in 6 autopsied patients in whom thallium-201 myocardial perfusion scanning were performed within three months before death. TAR closely correlated with left to right ventricular mass ratio (r = 0.978, p < 0.001). The comparison of validity of TAR with those of electrocardiographic interpretation according to WHO, Sasamoto, Roman or Milnor for the detection of right ventricular hypertrophy revealed the former was much superior to all of latters. From the results obtained, it may be inferred that TAR reflects the degree of pulmonary hypertension and anatomical right ventricular hypertrophy and is a useful non-invasive method to detect right ventricular hypertrophy in chronic pulmonary disease. (J.P.N.)

Differential CT features between malignant mesothelioma and pleural metastasis from lung cancer or extra thoracic primary tumor mimicking malignant mesothelioma

Energy Technology Data Exchange (ETDEWEB)

Lee, Sung Il; Ryu, Young Hoon; Lee, Kwang Hun; Choe, Kyu Ok; Kim, Sang Jin [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

2000-01-01

To evaluate the differential CT features found among malignant mesothelioma and pleural metastasis from lung cancer and from extra-thoracic primary tumor which on CT mimic malignant mesothelioma. Forty-four patients who on chest CT scans showed pleural thickening suggesting malignant pleural disease and in whom this condition was pathologically confirmed were included in this study. On the basis of their pathologically proven primary disease (malignant mesothelioma (n=3D14), pleural metastasis of lung cancer (n=3D18), extra thoracic primary tumor (n=3D12). They were divided into three groups. Cases of lung which on CT showed a primary lung nodule or endobronchial mass with pleural lesion, or manifested only pleural effusion, were excluded. The following eight CT features were retrospectively analyzed: (1) configuration of pleural lesion (type I, single or multiple separate nodules, type II, localized flat pleural thickening, type III, diffuse flat pleural thickening; type IV, type III with pleural nodules superimposed; type V, mass filling the hemithorax), (2) the presence of pleural effusion, (3) chest wall or rib invasion, (4) the involvement of a major fissure, (5) extra-pleural fat proliferation, (6) calcified plaque, (7) metastatic lymph nodes, (8) metastatic lung modules. In malignant mesothelioma, type IV (8/14) or II (4/14) pleural thickening was relatively frequent. Pleural metastasis of lung cancer favored type IV (8/18) or I (6/18) pleural thickening, while pleural metastasis from extrathoracic primary tumor showed a variable thickening configuration, except type V. Pleural metastasis from lung cancer and extrapleural primary tumor more frequently showed type I configuration than did malignant mesothelioma, and there were significant differences among the three groups. Fissural involvement, on the other hand, was significantly more frequent in malignant mesothelioma than in pleural metastasis from lung cancer or extrapleural primary tumor. Metastatic

Angiokeratoma circumscriptum naeviforme with soft tissue hypertrophy and deep venous malformation: A variant of Klippel-Trenaunay syndrome?

OpenAIRE

Wankhade, Vaishali; Singh, Rajesh; Sadhwani, Venus; Kodate, Purnima; Disawal, Amit

2014-01-01

Klippel-Trenaunay syndrome (KTS) is a cutaneous capillary malformation on a limb in association with soft tissue swelling with or without bony hypertrophy and atypical varicosity. The capillary malformation associated with KTS is port wine stain. Angiokeratoma circumscriptum naeviforme (ACN) is a congenital variant of angiokeratoma commonly present on the lower limb as a hyperkeratotic plaque. ACN is rarely associated with KTS. We report a case of ACN with soft tissue hypertrophy and deep ven...

Upper limb congenital muscular hypertrophy and aberrant muscle syndrome in children.

Science.gov (United States)

Dahan, Emmanuel; Chaves, Camilo; Bachy, Manon; Fitoussi, Frank

2018-01-01

Congenital muscle hypertrophy of the upper limb is a very rare condition with unknown aetiology. This descriptive observational and retrospective series included eight children followed by a multidisciplinary team from 2005 to 2017. The diagnosis was based on a cluster of clinical and radiological characteristics after elimination of differential diagnoses. Patients were categorized according to: anomalies of the wrist, anomalies of long fingers of intrinsic or extrinsic origin; and anomalies of the thumb with or without first web space contracture. Treatment begins in young children with hand orthoses to limit muscle contraction and joint malposition. The purpose of surgical treatment was to release contractures and to restore muscle balance through, in the main, finger intrinsic releases and first web releases. At the 2-year follow-up, we found that limited surgical procedures improved finger, thumb and wrist positions. We conclude that muscle hypertrophy is the main cause of deformity and that selective releases of contracted musculo-tendinous units and skin lengthening are effective. IV.

Kaempferol Attenuates Cardiac Hypertrophy via Regulation of ASK1/MAPK Signaling Pathway and Oxidative Stress.

Science.gov (United States)

Feng, Hong; Cao, Jianlei; Zhang, Guangyu; Wang, Yanggan

2017-07-01

Kaempferol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperlipidemia, and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains to be elucidated. The aim of our study was to investigate the effects of kaempferol on cardiac hypertrophy and the underlying mechanism. Mice subjected to aorta banding were treated with or without kaempferol (100 mg/kg/d, p. o.) for 6 weeks. Echocardiography was performed to evaluate cardiac function. Mice hearts were collected for pathological observation and molecular mechanism investigation. H9c2 cardiomyocytes were stimulated with or without phenylephrine for in vitro study. Kaempferol significantly attenuated cardiac hypertrophy induced by aorta banding as evidenced by decreased cardiomyocyte areas and interstitial fibrosis, accompanied with improved cardiac functions and decreased apoptosis. The ASK1/MAPK signaling pathways (JNK1/2 and p38) were markedly activated in the aorta banding mouse heart but inhibited by kaempferol treatment. In in vitro experiments, kaempferol also inhibited the activity of ASK1/JNK1/2/p38 signaling pathway and the enlargement of H9c2 cardiomyocytes. Furthermore, our study revealed that kaempferol could protect the mouse heart and H9c2 cells from pathological oxidative stress. Our investigation indicated that treatment with kaempferol protects against cardiac hypertrophy, and its cardioprotection may be partially explained by the inhibition of the ASK1/MAPK signaling pathway and the regulation of oxidative stress. Georg Thieme Verlag KG Stuttgart · New York.

Factors Influencing the Increase in Na-K-ATPase in Compensatory Renal Hypertrophy

Science.gov (United States)

Epstein, Franklin H.; Charney, Alan N.; Silva, Patricio

1978-01-01

An increase in Na-K-ATPase in kidney homogenates usually accompanies compensatory renal hypertrophy. While it may be evident in both the cortex and medulla of the kidney, it is most marked in the outer medulla and may be present only in that region. The increase in enzyme activity does not depend on an intact adrenal cortex and can be elicited in the absence of adrenal glucocorticoids. It is not seen in the form of renal hypertrophy produced by potassium depletion, in which the transport of sodium and potassium by the kidney is not increased. When present in compensatory renal growth, the enzyme change is correlated with an increase in the reabsorption of sodium, or the excretion of potassium, or both, per unit of renal tissue. It proceeds in the presence of either, but not in the absence of both. PMID:216164

Deletion of protein tyrosine phosphatase 1B rescues against myocardial anomalies in high fat diet-induced obesity: Role of AMPK-dependent autophagy.

Science.gov (United States)

Kandadi, Machender R; Panzhinskiy, Evgeniy; Roe, Nathan D; Nair, Sreejayan; Hu, Dahai; Sun, Aijun

2015-02-01

Obesity-induced cardiomyopathy may be mediated by alterations in multiple signaling cascades involved in glucose and lipid metabolism. Protein tyrosine phosphatase-1B (PTP1B) is an important negative regulator of insulin signaling. This study was designed to evaluate the role of PTP1B in high fat diet-induced cardiac contractile anomalies. Wild-type and PTP1B knockout mice were fed normal (10%) or high (45%) fat diet for 5months prior to evaluation of cardiac function. Myocardial function was assessed using echocardiography and an Ion-Optix MyoCam system. Western blot analysis was employed to evaluate levels of AMPK, mTOR, raptor, Beclin-1, p62 and LC3-II. RT-PCR technique was employed to assess genes involved in hypertrophy and lipid metabolism. Our data revealed increased LV thickness and LV chamber size as well as decreased fractional shortening following high fat diet intake, the effect was nullified by PTP1B knockout. High fat diet intake compromised cardiomyocyte contractile function as evidenced by decreased peak shortening, maximal velocity of shortening/relengthening, intracellular Ca²⁺ release as well as prolonged duration of relengthening and intracellular Ca²⁺ decay, the effects of which were alleviated by PTP1B knockout. High fat diet resulted in enlarged cardiomyocyte area and increased lipid accumulation, which were attenuated by PTP1B knockout. High fat diet intake dampened myocardial autophagy as evidenced by decreased LC3-II conversion and Beclin-1, increased p62 levels as well as decreased phosphorylation of AMPK and raptor, the effects of which were significantly alleviated by PTP1B knockout. Pharmacological inhibition of AMPK using compound C disengaged PTP1B knockout-conferred protection against fatty acid-induced cardiomyocyte contractile anomalies. Taken together, our results suggest that PTP1B knockout offers cardioprotection against high fat diet intake through activation of AMPK. This article is part of a Special Issue entitled

Carbohydrates as Fat Replacers.

Science.gov (United States)

Peng, Xingyun; Yao, Yuan

2017-02-28

The overconsumption of dietary fat contributes to various chronic diseases, which encourages attempts to develop and consume low-fat foods. Simple fat reduction causes quality losses that impede the acceptance of foods. Fat replacers are utilized to minimize the quality deterioration after fat reduction or removal to achieve low-calorie, low-fat claims. In this review, the forms of fats and their functions in contributing to food textural and sensory qualities are discussed in various food systems. The connections between fat reduction and quality loss are described in order to clarify the rationales of fat replacement. Carbohydrate fat replacers usually have low calorie density and provide gelling, thickening, stabilizing, and other texture-modifying properties. In this review, carbohydrates, including starches, maltodextrins, polydextrose, gums, and fibers, are discussed with regard to their interactions with other components in foods as well as their performances as fat replacers in various systems.

Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

Directory of Open Access Journals (Sweden)

Ori Nov

Full Text Available The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers, Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4 that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin

Effects of low level laser in the morphology of the skeletal muscle fiber during compensatory hypertrophy in plantar muscle of rats

Science.gov (United States)

Terena, Stella Maris Lins; Fernandes, Kristianne Porta Santos; Kalil, Sandra; Alves, Agnelo Neves; Mesquita Ferrari, Raquel Agnelli

2015-06-01

The hypertrophy is known as an increase the cross-sectional area of the muscle as a result of a muscular work against an overload, and it is compensatory because the overload is induced by functional elimination of synergistic muscles. The importance of study the compensatory hypertrophy is understand how this process can be influenced by the irradiation with regard to the weight and muscle cross-sectional area, to assist in the rehabilitation process and the effectiveness functional return. The aim was evaluate the effects of low-level laser irradiation on morphological aspects of muscle tissue, comparing the weight and cross-sectional area in rat skeletal muscle. Wistar rats were divided into three groups: control, hypertrophy group without irradiation (right plantar muscle) and hypertrophy group and irradiation (left plantar muscle), both analyzed after 7 and 14 days. The irradiation was performed daily immediately after the surgery. The parameters were: λ = 780nm, beam spot of 0.04 cm2, output power of 40mW, power density of 1W/cm2, energy density of 10J / cm2 and 10s exposure time with a total energy of 3.2 J. The results revealed that low level laser irradiation an increase the weight of the plantaris muscle after 7 and 14 days with a difference of 7.06% and 11.51% respectively. In conclusion, low level laser irradiation has an effect on compensatory hypertrophy to produce increased muscle weight and promoted an increase in cross-sectional area of muscle fibers in the compensatory hypertrophy model after 14 days with parameters cited above.

Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in prepubertal children

DEFF Research Database (Denmark)

Dencker, Magnus; Wollmer, Per; Karlsson, Magnus K

2012-01-01

Aim:  We analysed whether total body fat (TBF), abdominal fat and body fat distribution are associated with higher composite risk factor scores for cardiovascular disease (CVD) in young children. Methods:  Cross-sectional study of 238 children aged 8-11 years. TBF and abdominal fat mass (AFM) wer......, separately, and used as composite risk factor score. Results:  Pearson correlations between ln BF%, ln AFM and AFM/TBF versus composite risk factor score for boys were r = 0.56, r = 0.59 and r = 0.48, all p ...

Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation.

Science.gov (United States)

Kobayashi, Soushi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

2015-07-01

Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the heart; however, the function of CHP3 is unclear. Here, we aimed to identify the cardiac functions of CHP3. CHP3 was expressed in hearts at a wide range of developmental stages and was specifically detected in neonatal rat ventricular myocytes (NRVMs) but not in cardiac fibroblasts in culture. Moreover, knockdown of CHP3 expression using adenoviral-based RNA interference in NRVMs resulted in enlargement of cardiomyocyte size, concomitant with increased expression of a pathological hypertrophy marker ANP. This same treatment elevated glycogen synthase kinase (GSK3α/β) phosphorylation, which is known to inhibit GSK3 function. In contrast, CHP3 overexpression blocked the insulin-induced phosphorylation of GSK3α/β without affecting the phosphorylation of Akt, which is an upstream kinase of GSK3α/β, in HEK293 cells, and it inhibited both IGF-1-induced phosphorylation of GSK3β and cardiomyocyte hypertrophy in NRVMs. Co-immunoprecipitation experiments revealed that GSK3β interacted with CHP3. However, a Ca(2+)-binding-defective mutation of CHP3 (CHP3-D123A) also interacted with GSK3β and had the same inhibitory effect on GSK3α/β phosphorylation, suggesting that the action of CHP3 was independent of Ca(2+). These findings suggest that CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3α/β phosphorylation and subsequent enzymatic activation of GSK3α/β. Copyright © 2015 Elsevier Ltd. All rights reserved.

Secoisolariciresinol diglucoside attenuates cardiac hypertrophy and oxidative stress in monocrotaline-induced right heart dysfunction.

Science.gov (United States)

Puukila, Stephanie; Fernandes, Rafael Oliveira; Türck, Patrick; Carraro, Cristina Campos; Bonetto, Jéssica Hellen Poletto; de Lima-Seolin, Bruna Gazzi; da Rosa Araujo, Alex Sander; Belló-Klein, Adriane; Boreham, Douglas; Khaper, Neelam

2017-08-01

Pulmonary arterial hypertension (PAH) occurs when remodeling of pulmonary vessels leads to increased pulmonary vascular resistance resulting in increased pulmonary arterial pressure. Increased pulmonary arterial pressure results in right ventricle hypertrophy and eventually heart failure. Oxidative stress has been implicated in the pathogenesis of PAH and may play a role in the regulation of cellular signaling involved in cardiac response to pressure overload. Secoisolariciresinol diglucoside (SDG), a component from flaxseed, has been shown to reduce cardiac oxidative stress in various pathophysiological conditions. We investigated the potential protective effects of SDG in a monocrotaline-induced model of PAH. Five- to six-week-old male Wistar rats were given a single intraperitoneal injection of monocrotaline (60 mg/kg) and sacrificed 21 days later where heart, lung, and plasma were collected. SDG (25 mg/kg) was given via gavage as either a 21-day co-treatment or pre-treatment of 14 days before monocrotaline administration and continued for 21 days. Monocrotaline led to right ventricle hypertrophy, increased lipid peroxidation, and elevated plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). Co-treatment with SDG did not attenuate hypertrophy or ALT and AST levels but decreased reactive oxygen species (ROS) levels and catalase and superoxide dismutase activity compared to the monocrotaline-treated group. Pre-treatment with SDG decreased right ventricle hypertrophy, ROS levels, lipid peroxidation, catalase, superoxide dismutase, and glutathione peroxidase activity and plasma levels of ALT and AST when compared to the monocrotaline group. These findings indicate that pre-treatment with SDG provided better protection than co-treatment in this model of right heart dysfunction, suggesting an important role for SDG in PAH and right ventricular remodeling.

Bilateral hypertrophy of masseteric and temporalis muscles, our fifteen patients and review of literature.

Science.gov (United States)

Graziano, P; Dell'Aversana Orabona, G; Astarita, F; Ponzo, L M; Nunziata, R; Salzano, G; Maglitto, F; Solari, D; Santella, A; Cappabianca, M; Iaconetta, G; Califano, L

2016-01-01

The association of bilateral hypertrophy of temporalis and masseteric muscles is a rare clinical entity. The origin of the condition is unclear, causing cosmetic problems, pain, and functional impairment. In this paper we analyzed 15 patients treated at the Department of Maxillo-Facial Surgery of the University of Naples Federico II, from 2000 to 2013, for temporalis and/or masseteric muscle hypertrophy, and in particular, a rare case of a patient with a marked bilateral swelling of the temporalis and masseteric region, in conjunction with a review of the literature. Fourteen patients have not any kind of postoperatively problems. The last patient had been aware of the swelling for many years and complained of recurrent headaches. We adopted a new protocol fort this patients and the patient was very pleased with the treatment results, and reported a reduction in headaches and a continuation of his well-being, in addition to greater self-confidence. The last follow-up was performed three years after the first treatment, and the patient showed a complete resolution of his symptoms, and just a small increase of the swelling. The treatment of temporalis and masseteric hypertrophy with Botulin toxin could be an effective option compared to conservative treatment or surgical intervention, although the review of the literature shows that this is only a temporary treatment. In fact, surgery still remains the best option. The treatment must be repeated every 4/6 months for 2-3 consecutive years before having stable benefits. To overcome this problem, an association with a bite treatment allowed us to achieve more lasting and more stable results over time without a recurrence of symptoms between the treatments. Furthermore, this association has enabled us to obtain a more rapid reduction of the hypertrophy.

Effects of Menstrual Phase-Dependent Resistance Training Frequency on Muscular Hypertrophy and Strength.

Science.gov (United States)

Sakamaki-Sunaga, Mikako; Min, Seokki; Kamemoto, Kayoko; Okamoto, Takanobu

2016-06-01

The present study investigated how different training frequencies during menstrual phases affect muscle hypertrophy and strength. Fourteen eumenorrheic women performed 3 sets of arm curls (8-15 repetitions) until failure for 12 weeks. Depending on the menstrual cycle phase, each subject trained each arm separately after either a 3- or a 1-d·wk training protocol during the follicular phase (FP-T) and a 3- or 1-d·wk training protocol during the luteal phase (LP-T). Cross-sectional area (CSA), 1 repetition maximum, and maximum voluntary contraction significantly increased 6.2 ± 4.4, 36.4 ± 11.9, and 16.7 ± 5.6%, respectively (p ≤ 0.05 vs. before training), in the FP-T group and 7.8 ± 4.2, 31.8 ± 14.1, and 14.9 ± 12.7%, respectively (p ≤ 0.05 vs. before training), in the LP-T group. Changes in CSA between the FP-T and the LP-T groups significantly and positively correlated (r = 0.54, p ≤ 0.05). There were no major differences among the different training protocols with regard to muscle hypertrophy and strength. Therefore, we suggest that variations in female hormones induced by the menstrual cycle phases do not significantly contribute to muscle hypertrophy and strength gains during 12 weeks of resistance training.

Facts about trans fats

Science.gov (United States)

Trans fat is a type of dietary fat . Of all the fats, trans fat is the worst for your health. Too much ... from solid margarine to soft margarine. Ask what type of fats foods are cooked in when you eat out ...

Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

Science.gov (United States)

Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

2013-01-01

Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2‐mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2‐mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes.

Science.gov (United States)

Crossland, Hannah; Timmons, James A; Atherton, Philip J

2017-12-01

Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF-1-mediated myotube hypertrophy in vitro Primary skeletal myotubes were treated with IGF-1 (50 ng/ml) with or without 0.5 µM CX-5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre-rRNA expression (-64 ± 5% vs. IGF-1; P IGF-1; P IGF-1-treated myotubes. IGF-1-mediated increases in myotube diameter (1.27 ± 0.09-fold, P IGF-1 treatment did not prevent early increases in AKT (+203 ± 39% vs. CX; P IGF-1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF-1-induced myotube hypertrophy in vitro. -Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes. © The Author(s).

Acute colonic obstruction due to benign prostatic hypertrophy.

LENUS (Irish Health Repository)

Mac Giobuin, S

2012-02-01

A seventy two year old man presented to the Emergency Department with clinical features of colonic obstruction. Subsequent radiological investigations confirmed this impression and revealed the aetiology to be compression of the sigmoid colon against the sacrum by a massively distended urinary bladder. Chronic urinary retention due to benign prostatic hypertrophy is an extremely unusual cause of large bowel obstruction. Little in this patient\\'s clinical findings suggested this aetiology. We reviewed the literature in this area and highlight the benefits of CT scanning over contrast studies.

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

Directory of Open Access Journals (Sweden)

Satoshi Nakada

Full Text Available External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK, moderate (MO, middle (MI, and strong (ST overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity increased with increasing overload, with increases of 1.8-fold (MO, 2.2-fold (MI, and 2.5-fold (ST, respectively, relative to non-overloaded muscle (NL in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98. The phosphorylated form of p70S6K (a positive regulator of translational efficiency showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO, 17.4-fold (MI, and 18.2-fold (ST, respectively, relative to NL in the WK group. These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size.

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle.

Science.gov (United States)

Nakada, Satoshi; Ogasawara, Riki; Kawada, Shigeo; Maekawa, Takahiro; Ishii, Naokata

2016-01-01

External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK), moderate (MO), middle (MI), and strong (ST) overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity) increased with increasing overload, with increases of 1.8-fold (MO), 2.2-fold (MI), and 2.5-fold (ST), respectively, relative to non-overloaded muscle (NL) in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98). The phosphorylated form of p70S6K (a positive regulator of translational efficiency) showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO), 17.4-fold (MI), and 18.2-fold (ST), respectively, relative to NL in the WK group). These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size.

Pathogenesis of venous hypertrophy associated with schistosomiasis in whooper swans (Cygnus cygnus) in Japan.

Science.gov (United States)

Akagami, Masataka; Nakamura, Kikuyasu; Nishino, Hiroto; Seki, Satoko; Shimizu, Hiromi; Yamamoto, Yu

2010-03-01

Thirteen whooper swans (Cygnus cygnus) affected with schistosomiasis were examined pathologically. Venous hypertrophy, characterized by marked nodular proliferation of medial smooth muscle fibers with frequent obliteration of the vascular lumen, was observed in eight of the 13 whooper swans. Venous hypertrophy was located in the medium-sized veins of the mesentery, the serosa, and the muscular layer of the duodenum, jejunum, ileum, and cecum. In addition, vascular lesions were seen in the capsule and parenchymal interstitia of the liver, spleen, kidney, heart, aorta, air sac, and pleura. In mild lesions, segmental proliferation of medial smooth muscles was observed in the venous medium of the mesentery and serosa. Moderate lesions had a proliferation of smooth muscles in the veins with obliteration of venous lumens. In marked lesions, more severe proliferation of veins extended into the intestinal muscular layers and depressed them. Schistosome parasites were found in the venous lumens of each of the eight whooper swans with vascular lesions. Bile pigments and hemosiderin were observed in the livers of whooper swans. In addition, adult nematodes (Sarconema sp.) were localized in the myocardium of four of the eight whooper swans. The venous hypertrophy may be caused by the proliferation of medial smooth muscle fibers induced by schistosomiasis.

Pathophysiologic assessment of left ventricular hypertrophy and strain in asymptomatic patients with essential hypertension

International Nuclear Information System (INIS)

Pringle, S.D.; Macfarlane, P.W.; McKillop, J.H.; Lorimer, A.R.; Dunn, F.G.

1989-01-01

To investigate the significance of the electrocardiographic (ECG) pattern of left ventricular hypertrophy and strain, two groups of asymptomatic patients with essential hypertension were compared. The patients were similar in terms of age, smoking habit, serum cholesterol and blood pressure levels, but differed in the presence (Group I, n = 23) or absence (Group II, n = 23) of the ECG pattern of left ventricular hypertrophy and strain. Group I patients had significantly more episodes of exercise-induced ST segment depression (14 versus 4, p less than 0.05) and reversible thallium perfusion abnormalities (11 of 23 versus 3 of 23, p less than 0.05) despite similar exercise capacity and absence of chest pain. Nonsustained ventricular tachycardia was detected on 24 h ambulatory ECG monitoring in two patients in Group I, but no patient in Group II. Coronary arteriography performed in 20 Group I patients demonstrated significant coronary artery disease in 8 patients. This study has shown that there is a subgroup of hypertensive patients with ECG left ventricular hypertrophy and strain who have covert coronary artery disease. This can be detected by thallium perfusion scintigraphy, and may contribute to the increased risk known to be associated with this ECG abnormality

The callipyge mutation and other genes that affect muscle hypertrophy in sheep

Directory of Open Access Journals (Sweden)

Cockett Noelle E

2005-12-01

Full Text Available Abstract Genetic strategies to improve the profitability of sheep operations have generally focused on traits for reproduction. However, natural mutations exist in sheep that affect muscle growth and development, and the exploitation of these mutations in breeding strategies has the potential to significantly improve lamb-meat quality. The best-documented mutation for muscle development in sheep is callipyge (CLPG, which causes a postnatal muscle hypertrophy that is localized to the pelvic limbs and loin. Enhanced skeletal muscle growth is also observed in animals with the Carwell (or rib-eye muscling mutation, and a double-muscling phenotype has been documented for animals of the Texel sheep breed. However, the actual mutations responsible for these muscular hypertrophy phenotypes in sheep have yet to be identified, and further characterization of the genetic basis for these phenotypes will provide insight into the biological control of muscle growth and body composition.

GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

International Nuclear Information System (INIS)

Zhu Zhiming; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin

2005-01-01

We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, β-myosin heavy chain, and α-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway

Differential fat harvesting

Directory of Open Access Journals (Sweden)

Sebastian Torres Farr

2014-12-01

Full Text Available Aim: Volume replacement with fillers is regularly performed with the use of diverse volumetric materials to correct different structures around the face, depending on the volume enhancement required and the thickness of the soft tissue envelope. Differential fat harvesting and posterior grafting is performed to place the correct fat parcel size for each target area, expanding the potential applications of fat. Methods: Sixty patients consecutively recruited on a first come basis undergone a facial fat grafting procedure, in private practice setting between March 2012 and October 2013. Fat grafting quantity and quality was predicted for each case. Differential harvesting was performed, with 2 fat parcels size. Processing was performed through washing. Fat infiltration was carried out through small cannulas or needles depending on the treated area. Outcomes were analysed both by the physicians and the patients at 7 days, 1 month, 3 months and 6 months through a perceived satisfaction questionnaire. Parameters considered were downtime or discomfort, skin benefits, volume restoration, reabsorption rate estimated and overall improvement. Results: Full facial differential fat grafting procedure lasted an average of 1.5-2.5 h. Average downtime was 3-4 days. Follow-up was performed to a minimum of 6 months. Both patient and physician overall satisfaction rates were mostly excellent. Adverse events like lumps or irregularities were not encountered. Conclusion: Differential fat harvesting and posterior grafting is a valid alternative, to expand the repertoire of fat use, allow a more homogeneous effect, reduce the potential complications, speed up the process, improve graft survival, and to enhance overall aesthetic outcome.

High fat diet and GLP-1 drugs induce pancreatic injury in mice

Energy Technology Data Exchange (ETDEWEB)

Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron; Zhang, Jun

2014-04-15

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.

High fat diet and GLP-1 drugs induce pancreatic injury in mice

International Nuclear Information System (INIS)

Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun

2014-01-01

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment

Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

Science.gov (United States)

Fortes, Marco A. S.; Scervino, Maria V. M.; Marzuca-Nassr, Gabriel N.; Vitzel, Kaio F.; da Justa Pinheiro, Carlos H.; Curi, Rui

2017-01-01

Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus) or glycolytic (EDL) muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK), Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK) and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1), mechano-growth factor (MGF) and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group. PMID:29123487

Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

NARCIS (Netherlands)

Duarte-Salles, Talita; Fedirko, Veronika; Stepien, Magdalena; Aleksandrova, Krasimira; Bamia, Christina; Lagiou, Pagona; Laursen, Anne Sofie Dam; Hansen, Louise; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Fagherazzi, Guy; His, Mathilde; Boeing, Heiner; Katzke, Verena; Kühn, Tilman; Trichopoulou, Antonia; Valanou, Elissavet; Kritikou, Maria; Masala, Giovanna; Panico, Salvatore; Sieri, Sabina; Ricceri, Fulvio; Tumino, Rosario; Bueno-De-Mesquita, H. B.; Peeters, Petra H.; Skeie, Guri; Weiderpass, Elisabete; Ardanaz, Eva; Bonet, Catalina; Chirlaque, Maria Dolores; Dorronsoro, Miren; Quirõs, J. Ramõn; Johansson, Ingegerd; Ohlsson, Bodil; Sjöberg, Klas; Wennberg, Maria; Khaw, Kay Tee; Travis, Ruth C.; Wareham, Nick; Ferrari, Pietro; Freisling, Heinz; Romieu, Isabelle; Cross, Amanda J.; Gunter, Marc; Lu, Yunxia; Jenab, Mazda

2015-01-01

The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective

Desire to eat high- and low-fat foods following a low-fat dietary intervention.

Science.gov (United States)

Grieve, Frederick G; Vander Weg, Mark W

2003-01-01

This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. University clinic, Memphis, Tennessee. 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. A 16-week cognitive-behavioral program for obesity. Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. Analysis of variance, multiple regression, and paired t tests. The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.

Buddleja officinalis Maximowicz Extract Inhibits Lipid Accumulation on Adipocyte Differentiation in 3T3-L1 Cells and High-Fat Mice

Directory of Open Access Journals (Sweden)

Jin-Kyu Kim

2012-07-01

Full Text Available Obesity is a global health problem. It is also known to be a risk factor for the development of metabolic disorders, type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. In this study, we elucidated that Buddleja officinalis Maximowicz extract significantly inhibited lipid accumulation during 3T3-L1 adipocyte differentiation. Furthermore, Buddleja officinalis Maximowicz extract reduced the body weight gain induced through feeding a high-fat diet to C57BL/6 mice. The treatment of Buddleja officinalis Maximowicz extract significantly reduced the adipose tissue weight to 2.7/100 g of body weight in high-fat mice. When their adipose tissue morphology was investigated for histochemical staining, the distribution of cell size in the high-fat diet groups was hypertrophied compared with those from Buddleja officinalis Maximowicz extract-treated mice. In addition, in Buddleja officinalis Maximowicz extract-treated mice, a significant reduction of serum triglyceride and T-cholesterol was observed at to 21% and 17%, respectively. The discovery of bioactive compounds from diet or dietary supplementation is one of possible ways to control obesity and to prevent or reduce the risks of various obesity-related diseases. These results support that Buddleja officinalis Maximowicz extract is expected to create the therapeutic interest with respect to the treatment of obesity.

Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.

Science.gov (United States)

Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie

2017-05-01

Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.

Science.gov (United States)

Li, Chao; Vu, Kent; Hazelgrove, Krystina; Kuemmerle, John F

2015-12-01

The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. Copyright © 2015 the American Physiological Society.

HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy.

Science.gov (United States)

Huang, Chih-Yang; Lee, Fa-Lun; Peng, Shu-Fen; Lin, Kuan-Ho; Chen, Ray-Jade; Ho, Tsung-Jung; Tsai, Fu-Jen; Padma, Vijaya V; Kuo, Wei-Wen; Huang, Chih-Yang

2018-02-01

Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT 1 R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found that ANG II mediated ERK/GSK3-induced IGF-IIR protein stability by downregulating the E3 ubiquitin ligase of IGF-IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II-induced HSF1 S303 phosphorylation, resulting in IGF-IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG II-induced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF-IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF-IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients. © 2017 Wiley Periodicals, Inc.

Quercetin prevents left ventricular hypertrophy in the Apo E knockout mouse

Directory of Open Access Journals (Sweden)

Elena Ulasova

2013-01-01

Full Text Available Hypercholesterolemia is a risk factor for the development of hypertrophic cardiomyopathy. Nevertheless, there are few studies aimed at determining the effects of dietary compounds on early or mild cardiac hypertrophy associated with dyslipidemia. Here we describe left ventricular (LV hypertrophy in 12 week-old Apo E−/− hypercholesterolemic mice. The LV end diastolic posterior wall thickness and overall LV mass were significantly increased in Apo E−/− mice compared with wild type (WT controls. Fractional shortening, LV end diastolic diameter, and hemodynamic parameters were unchanged from WT mice. Oral low dose quercetin (QCN; 0.1 µmol QCN/kg body weight for 6 weeks significantly reduced total cholesterol and very low density lipoprotein in the plasma of Apo E−/− mice. QCN treatment also significantly decreased LV posterior wall thickness and LV mass in Apo E−/− mice. Myocardial geometry and function were unaffected in WT mice by QCN treatment. These data suggest that dietary polyphenolic compounds such as QCN may be effective modulators of plasma cholesterol and could prevent maladaptive myocardial remodeling.

Left ventricular hypertrophy: The relationship between the electrocardiogram and cardiovascular magnetic resonance imaging.

Science.gov (United States)

Bacharova, Ljuba; Ugander, Martin

2014-11-01

Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow-Lyon, Romhilt-Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping, extracellular volume fraction (ECV) mapping, fat/water-weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH. © 2014 Wiley Periodicals, Inc.

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

DEFF Research Database (Denmark)

Christoffersen, Tue E.H.; Aplin, Mark; Strom, Claes C.

2006-01-01

also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system......RNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle....

The compatibility of concurrent high intensity interval training and resistance training for muscular strength and hypertrophy: a systematic review and meta-analysis.

Science.gov (United States)

Sabag, Angelo; Najafi, Abdolrahman; Michael, Scott; Esgin, Tuguy; Halaki, Mark; Hackett, Daniel

2018-04-16

The purpose of this systematic review and meta-analysis is to assess the effect of concurrent high intensity interval training (HIIT) and resistance training (RT) on strength and hypertrophy. Five electronic databases were searched using terms related to HIIT, RT, and concurrent training. Effect size (ES), calculated as standardised differences in the means, were used to examine the effect of concurrent HIIT and RT compared to RT alone on muscle strength and hypertrophy. Sub-analyses were performed to assess region-specific strength and hypertrophy, HIIT modality (cycling versus running), and inter-modal rest responses. Compared to RT alone, concurrent HIIT and RT led to similar changes in muscle hypertrophy and upper body strength. Concurrent HIIT and RT resulted in a lower increase in lower body strength compared to RT alone (ES = -0.248, p = 0.049). Sub analyses showed a trend for lower body strength to be negatively affected by cycling HIIT (ES = -0.377, p = 0.074) and not running (ES = -0.176, p = 0.261). Data suggests concurrent HIIT and RT does not negatively impact hypertrophy or upper body strength, and that any possible negative effect on lower body strength may be ameliorated by incorporating running based HIIT and longer inter-modal rest periods.

Facial fat necrosis following autologous fat transfer and its management

Directory of Open Access Journals (Sweden)

Sweta Rai

2014-01-01

Full Text Available Autologous fat transfer (AFT is an increasingly popular cosmetic procedure practiced by dermatologic surgeons worldwide. As this is an office based procedure performed under local or tumescent anaesthesia with fat transferred within the same individual and limited associated down time its is considered relatively safe and risk free in the cosmetic surgery arena. We describe a case of AFT related fat necrosis causing significant facial dysmorphia and psychosocial distress. We also discuss the benefits and risks of AFT highlighting common causes of fat graft failure.

Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy

NARCIS (Netherlands)

J. Deinum (Jacob); J.M. van Gool (Jeanette); M.J.M. Kofflard (Marcel); A.H.J. Danser (Jan); F.J. ten Cate (Folkert)

2001-01-01

textabstractThe development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1

Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat with Incident Atrial Fibrillation (From the Framingham Heart Study)

Science.gov (United States)

Lee, Jane J.; Yin, Xiaoyan; Hoffmann, Udo; Fox, Caroline S.; Benjamin, Emelia J.

2016-01-01

Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third Generation Cohorts who participated in the multi-detector computed tomography sub-study examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index (BMI) was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and sex-adjusted incident AF rate per 1000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and sex-adjusted model, greater pericardial fat [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.03-1.34] and intrathoracic fat (HR 1.24, 95% CI 1.06-1.45) were associated with increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99-1.30) for pericardial fat, 1.19 (1.01-1.40) for intrathoracic fat, and 1.09 (0.93-1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of BMI, none of the associations remained significant (all p>0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. PMID:27666172

Angiokeratoma circumscriptum naeviforme with soft tissue hypertrophy and deep venous malformation: A variant of Klippel-Trenaunay syndrome?

Directory of Open Access Journals (Sweden)

Vaishali Wankhade

2014-01-01

Full Text Available Klippel-Trenaunay syndrome (KTS is a cutaneous capillary malformation on a limb in association with soft tissue swelling with or without bony hypertrophy and atypical varicosity. The capillary malformation associated with KTS is port wine stain. Angiokeratoma circumscriptum naeviforme (ACN is a congenital variant of angiokeratoma commonly present on the lower limb as a hyperkeratotic plaque. ACN is rarely associated with KTS. We report a case of ACN with soft tissue hypertrophy and deep venous malformation (possibly a variant of Klippel-Trenaunay in a 4-year-old male child.

Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure.

Science.gov (United States)

Zhang, Lei; Liu, Ming; Jiang, Hong; Yu, Ying; Yu, Peng; Tong, Rui; Wu, Jian; Zhang, Shuning; Yao, Kang; Zou, Yunzeng; Ge, Junbo

2016-03-01

Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Low morning serum cortisol levels in children with tonsillar hypertrophy and moderate-to-severe OSA.

Science.gov (United States)

Malakasioti, Georgia; Alexopoulos, Emmanouel I; Varlami, Vasiliki; Chaidas, Konstantinos; Liakos, Nikolaos; Gourgoulianis, Konstantinos; Kaditis, Athanasios G

2013-09-01

Hypertrophic tonsillar tissue in children with obstructive sleep apnea (OSA) has enhanced expression of glucocorticoid receptors, which may reflect low endogenous cortisol levels. We have evaluated the effect of the interaction between tonsillar hypertrophy and OSA severity on morning serum cortisol levels. Children with and without snoring underwent polysomnography, tonsillar size grading, and measurement of morning serum cortisol. Seventy children (2-13 years old) were recruited: 30 with moderate-to-severe OSA (apnea-hypopnea index [AHI] > 5 episodes/h), 26 with mild OSA (AHI > 1 and ≤ 5), and 14 controls (no snoring; AHI ≤ 1). Tonsillar hypertrophy was present in 56.7%, 53.8%, and 42.9% of participants in each group, respectively. Application of a general linear model demonstrated a significant effect of the interaction between severity of OSA and tonsillar hypertrophy on cortisol levels (P = 0.04), after adjustment for obesity, gender, and age. Among children with tonsillar hypertrophy, subjects with moderate-to-severe OSA (n = 17; AHI 14.7 ± 10.6), mild OSA (n = 14; AHI 2.3 ± 1.2), and control participants (n = 6; AHI 0.7 ± 0.2) were significantly different regarding cortisol levels (P = 0.02). Subjects with moderate-to-severe OSA had lower cortisol (16.9 ± 8.7 mcg/dL) than those with mild OSA (23.3 ± 4.2; P = 0.01) and those without OSA (controls) (23.6 ± 5.3 mcg/dL; P = 0.04). In contrast, children with normal-size tonsils and moderate-to-severe OSA, mild OSA, and controls did not differ in cortisol levels. Children with moderate-to-severe obstructive sleep apnea and the phenotype of hypertrophic tonsils have reduced morning serum cortisol levels and potentially decreased glucocorticoid inhibitory effects on tonsillar growth.

Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

Directory of Open Access Journals (Sweden)

Marco A. S. Fortes

2017-10-01

Full Text Available Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus or glycolytic (EDL muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK, Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1, mechano-growth factor (MGF and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group.

IGF and myostatin pathways are respectively induced during the earlier and the later stages of skeletal muscle hypertrophy induced by clenbuterol, a β₂-adrenergic agonist.

Science.gov (United States)

Abo, Tokuhisa; Iida, Ryo-Hei; Kaneko, Syuhei; Suga, Takeo; Yamada, Hiroyuki; Hamada, Yoshiki; Yamane, Akira

2012-12-01

Clenbuterol, a β₂-adrenergic agonist, increases the hypertrophy of skeletal muscle. Insulin-like growth factor (IGF) is reported to work as a potent positive regulator in the clenbuterol-induced hypertrophy of skeletal muscles. However, the precise regulatory mechanism for the hypertrophy of skeletal muscle induced by clenbuterol is unknown. Myostatin, a member of the TGFβ super family, is a negative regulator of muscle growth. The aim of the present study is to elucidate the function of myostatin and IGF in the hypertrophy of rat masseter muscle induced by clenbuterol. To investigate the function of myostatin and IGF in regulatory mechanism for the clenbuterol-induced hypertrophy of skeletal muscles, we analysed the expression of myostatin and phosphorylation levels of myostatin and IGF signaling components in the masseter muscle of rat to which clenbuterol was orally administered for 21 days. Hypertrophy of the rat masseter muscle was induced between 3 and 14 days of oral administration of clenbuterol and was terminated at 21 days. The expression of myostatin and the phosphorylation of smad2/3 were elevated at 21 days. The phosphorylation of IGF receptor 1 (IGFR1) and akt1 was elevated at 3 and 7 days. These results suggest that myostatin functions as a negative regulator in the later stages in the hypertrophy of rat masseter muscle induced by clenbuterol, whereas IGF works as a positive regulator in the earlier stages. Copyright © 2012 John Wiley & Sons, Ltd.

Fat Taste Sensitivity Is Associated with Short-Term and Habitual Fat Intake

Directory of Open Access Journals (Sweden)

Andrew Costanzo

2017-07-01

Full Text Available Evidence suggests individuals less sensitive to fat taste (high fat taste thresholds (FTT may be overweight or obese and consume greater amounts of dietary fat than more sensitive individuals. The aims of this study were to assess associations between FTT, anthropometric measurements, fat intake, and liking of fatty foods. FTT was assessed in 69 Australian females (mean age 41.3 (15.6 (SD years and mean body mass index 26.3 (5.7 kg/m2 by a 3-alternate forced choice methodology and transformed to an ordinal scale (FT rank. Food liking was assessed by hedonic ratings of high-fat and reduced-fat foods, and a 24-h food recall and food frequency questionnaire was completed. Linear mixed regression models were fitted. FT rank was associated with dietary % energy from fat ( β ^ = 0.110 [95% CI: 0.003, 0.216], % energy from carbohydrate ( β ^ = −0.112 [−0.188, −0.035], and frequency of consumption of foods per day from food groups: high-fat dairy ( β ^ = 1.091 [0.106, 2.242], meat & meat alternatives ( β ^ = 0.669 [0.168, 1.170], and grain & cereals ( β ^ = 0.771 [0.212, 1.329] (adjusted for energy and age. There were no associations between FT rank and anthropometric measurements or hedonic ratings. Therefore, fat taste sensitivity appears to be associated with short-term fat intake, but not body size in this group of females.

Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

Directory of Open Access Journals (Sweden)

Walker LeeAnn

2002-01-01

Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.

Science.gov (United States)

von Frankenberg, Anize D; Marina, Anna; Song, Xiaoling; Callahan, Holly S; Kratz, Mario; Utzschneider, Kristina M

2017-02-01

We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: -0.37 ± 0.15 mmol/min, mean ± SE, p vs. HFD: -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = -0.77; p fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. NCT00930371.

Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

DEFF Research Database (Denmark)

Paul, David S; Grevengoed, Trisha J; Pascual, Florencia

2014-01-01

In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1(H-/-)), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy...... and B-type natriuretic peptide. mTOR activation of the related Acsl3 gene, usually associated with pathologic hypertrophy, was also attenuated in the Acsl1(H-/-) hearts, indicating that alternative pathways of fatty acid activation did not compensate for the loss of Acsl1. Compared to controls, Acsl1(H......-/-) hearts exhibited an 8-fold higher uptake of 2-deoxy[1-(14)C]glucose and a 35% lower uptake of the fatty acid analog 2-bromo[1-(14)C]palmitate. These data indicate that Acsl1-deficiency causes diastolic dysfunction and that mTOR activation is linked to the development of cardiac hypertrophy in Acsl1(H...

The impact of surgical treatment on the self-esteem of patients with breast hypertrophy, hypomastia, or breast asymmetry.

Science.gov (United States)

Neto, Miguel Sabino; Abla, Luiz Eduardo Felipe; Lemos, Ana Lucia; Garcia, Élvio Bueno; Enout, Mariana Junqueira Reis; Cabral, Nádia Canale; Ferreira, Lydia Masako

2012-02-01

Currently, the concept of health includes not only the absence of disease but also a complete state of physical, psychological, and social well-being with increased emphasis on the importance of self-esteem. This study aimed to evaluate the impact of surgical treatment on the self-esteem of patients with breast asymmetry, breast hypertrophy, or hypomastia. The Rosenberg Self-Esteem UNIFESP-EPM Scale was administered preoperatively and in the early and late postoperative periods to assess self-esteem. The sample comprised three groups of patients: the breast asymmetry group (n=35), the breast hypertrophy group (n=50), and the hypomastia group (n=40). Surgical treatment had a positive and similar impact on the self-esteem of the patients in the three study groups. Correction of breast asymmetry, breast hypertrophy, and hypomastia improved the patient's self-esteem. All three groups reported a similar increase in self-esteem (decrease in total scores) after breast reconstruction.

Quantitative measurement of radiofrequency volumetric tissue reduction by multidetector CT in patients with inferior turbinate hypertrophy.

Science.gov (United States)

Bahadir, Osman; Kosucu, Polat

2012-12-01

To objectively assess the efficacy of radiofrequency thermal ablation of inferior turbinate hypertrophy. Thirty-five patients with nasal obstruction secondary to inferior turbinate hypertrophy were prospectively enrolled. Radiofrequency energy was delivered to four sites in each inferior turbinate. Patients were evaluated before and 8 weeks after intervention. Subjective evaluation of nasal obstruction was performed using a visual analogue scale (VAS), and objective evaluation of the turbinate volume reduction was calculated using multidetector CT. Volumetric measurements of the preoperative inferior turbinate were compared with postoperative values on both sides. The great majority of patients (91.4%) exhibited subjective postoperative improvement. Mean obstruction (VAS) improved significantly from 7.45±1.48 to 3.54±1.96. Significant turbinate volume reduction was achieved by the surgery on both right and left sides [(preoperative vs. postoperative, right: 6.55±1.62cm(3) vs. 5.10±1.47cm(3), (PRadiofrequency is a safe and effective surgical procedure in reducing turbinate volume in patients with inferior turbinate hypertrophy. Multidetector CT is an objective method of assessment in detecting radiofrequency turbinate volume reduction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Intra-abdominal fat: Comparison of computed tomography fat segmentation and bioimpedance spectroscopy.

Science.gov (United States)

Finch, Peter

2017-06-01

Intra-abdominal fat is an important factor in determining the metabolic syndrome/insulin resistance, and thus the risk of diabetes and ischaemic heart disease. Computed Tomography (CT) fat segmentation represents a defined method of quantifying intra-abdominal fat, with attendant radiation risks. Bioimpedance spectroscopy may offer a method of assessment without any risks to the patients. A comparison is made of these two methods. This was a preliminary study of the utility of multifrequency bioimpedance spectroscopy of the mid abdomen as a measure of intra-abdominal fat, by comparison with fat segmentation of an abdominal CT scan in the -30 to -190 HU range. There was a significant (P abdominal fat and mid-upper arm circumference, as well as the bioimpedance parameter, the R/S ratio. Multivariate analysis showed that these were the only independant variables and allowed the derivation of a formula to estimate intra-abdominal fat: IAF = 0.02 × MAC - 0.757 × R/S + 0.036. Circumabdominal bioimpedance spectroscopy may prove a useful method of assessing intra-abdominal fat, and may be suitable for use in studies to enhance other measures of body composition, such as mid-upper arm circumference.

Loss of NHE1 activity leads to reduced oxidative stress in heart and mitigates high-fat diet-induced myocardial stress.

Science.gov (United States)

Prasad, Vikram; Lorenz, John N; Miller, Marian L; Vairamani, Kanimozhi; Nieman, Michelle L; Wang, Yigang; Shull, Gary E

2013-12-01

Acute inhibition of the NHE1 Na(+)/H(+) exchanger protects against ischemia-reperfusion injury and chronic inhibition attenuates development of cardiac hypertrophy and failure. To determine the cardiac effects of chronic inhibition of NHE1 under non-pathological conditions we used NHE1-null mice as a model of long-term NHE1 inhibition. Cardiovascular performance was relatively normal in Nhe1(-/-) mice although cardiac contractility and relaxation were slightly improved in mutant mice of the FVB/N background. GSH levels and GSH:GSSG ratios were elevated in Nhe1(-/-) hearts indicating an enhanced redox potential. Consistent with a reduced need for antioxidant protection, expression of heat shock proteins Hsp60 and Hsp25 was lower in Nhe1(-/-) hearts. Similarly, expression of mitochondrial superoxide dismutase 2 was reduced, with no increase in expression of other ROS scavenging enzymes. GLUT1 levels were increased in Nhe1(-/-) hearts, the number of lipid droplets in myocytes was reduced, and PDK4 expression was refractory to high-fat diet-induced upregulation observed in wild-type hearts. High-fat diet-induced stress was attenuated in Nhe1(-/-) hearts, as indicated by smaller increases in phosphorylation of Hsp25 and α-B crystallin, and there was better preservation of insulin sensitivity, as evidenced by PKB/Akt phosphorylation. Plasma glucose and insulin levels were lower and high-fat diet-induced hepatic lipid accumulation was reduced in Nhe1(-/-) mice, demonstrating extracardiac effects of NHE1 ablation. These data indicate that long-term ablation of NHE1 activity increases the redox potential, mitigates high-fat diet-induced myocardial stress and fatty liver disease, leads to better preservation of insulin sensitivity, and may alter both cardiac and systemic metabolic substrate handling in mice. © 2013 Elsevier Ltd. All rights reserved.

The Functional Role of Calcineurin in Hypertrophy, Regeneration, and Disorders of Skeletal Muscle

Directory of Open Access Journals (Sweden)

Kunihiro Sakuma

2010-01-01

Full Text Available Skeletal muscle uses calcium as a second messenger to respond and adapt to environmental stimuli. Elevations in intracellular calcium levels activate calcineurin, a serine/threonine phosphatase, resulting in the expression of a set of genes involved in the maintenance, growth, and remodeling of skeletal muscle. In this review, we discuss the effects of calcineurin activity on hypertrophy, regeneration, and disorders of skeletal muscle. Calcineurin is a potent regulator of muscle remodeling, enhancing the differentiation through upregulation of myogenin or MEF2A and downregulation of the Id1 family and myostatin. Foxo may also be a downstream candidate for a calcineurin signaling molecule during muscle regeneration. The strategy of controlling the amount of calcineurin may be effective for the treatment of muscular disorders such as DMD, UCMD, and LGMD. Activation of calcineurin produces muscular hypertrophy of the slow-twitch soleus muscle but not fast-twitch muscles.

Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKD.

Science.gov (United States)

Schneider, Markus P; Raff, Ulrike; Kopp, Christoph; Scheppach, Johannes B; Toncar, Sebastian; Wanner, Christoph; Schlieper, Georg; Saritas, Turgay; Floege, Jürgen; Schmid, Matthias; Birukov, Anna; Dahlmann, Anke; Linz, Peter; Janka, Rolf; Uder, Michael; Schmieder, Roland E; Titze, Jens M; Eckardt, Kai-Uwe

2017-06-01

The pathogenesis of left ventricular hypertrophy in patients with CKD is incompletely understood. Sodium intake, which is usually assessed by measuring urinary sodium excretion, has been inconsistently linked with left ventricular hypertrophy. However, tissues such as skin and muscle may store sodium. Using 23 sodium-magnetic resonance imaging, a technique recently developed for the assessment of tissue sodium content in humans, we determined skin sodium content at the level of the calf in 99 patients with mild to moderate CKD (42 women; median [range] age, 65 [23-78] years). We also assessed total body overhydration (bioimpedance spectroscopy), 24-hour BP, and left ventricular mass (cardiac magnetic resonance imaging). Skin sodium content, but not total body overhydration, correlated with systolic BP ( r =0.33, P =0.002). Moreover, skin sodium content correlated more strongly than total body overhydration did with left ventricular mass ( r =0.56, P skin sodium content is a strong explanatory variable for left ventricular mass, unaffected by BP and total body overhydration. In conclusion, we found skin sodium content to be closely linked to left ventricular mass in patients with CKD. Interventions that reduce skin sodium content might improve cardiovascular outcomes in these patients. Copyright © 2017 by the American Society of Nephrology.

FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

DEFF Research Database (Denmark)

Kring, Sofia I I; Holst, Claus; Zimmermann, Esther

2008-01-01

A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already...

Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort.

Science.gov (United States)

Duarte-Salles, Talita; Fedirko, Veronika; Stepien, Magdalena; Aleksandrova, Krasimira; Bamia, Christina; Lagiou, Pagona; Laursen, Anne Sofie Dam; Hansen, Louise; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; His, Mathilde; Boeing, Heiner; Katzke, Verena; Kühn, Tilman; Trichopoulou, Antonia; Valanou, Elissavet; Kritikou, Maria; Masala, Giovanna; Panico, Salvatore; Sieri, Sabina; Ricceri, Fulvio; Tumino, Rosario; Bueno-de-Mesquita, H B As; Peeters, Petra H; Hjartåker, Anette; Skeie, Guri; Weiderpass, Elisabete; Ardanaz, Eva; Bonet, Catalina; Chirlaque, Maria-Dolores; Dorronsoro, Miren; Quirós, J Ramón; Johansson, Ingegerd; Ohlsson, Bodil; Sjöberg, Klas; Wennberg, Maria; Khaw, Kay-Tee; Travis, Ruth C; Wareham, Nick; Ferrari, Pietro; Freisling, Heinz; Romieu, Isabelle; Cross, Amanda J; Gunter, Marc; Lu, Yunxia; Jenab, Mazda

2015-12-01

The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk. © 2015 UICC.

Fat and fat-free mass at birth

DEFF Research Database (Denmark)

Andersen, Gregers Stig; Girma, Tsinuel; Wells, Jonathan CK

2011-01-01

LBW increases the risk of a number of noncommunicable diseases in adulthood. However, birth weight (BW) cannot describe variability in infant body composition (BC). Variability in fat mass (FM) and fat-free mass (FFM) at birth may be particularly important in low-income countries because they und......LBW increases the risk of a number of noncommunicable diseases in adulthood. However, birth weight (BW) cannot describe variability in infant body composition (BC). Variability in fat mass (FM) and fat-free mass (FFM) at birth may be particularly important in low-income countries because...... they undergo nutritional transition. There is a need for data on birth BC and its predictors from low-income countries in transition. We assessed absolute FM and FFM at birth and examined the role of gender, parity, GA, and LBW as predictors of birth BC. FM and FFM were assessed within 48 h of birth on 350...... Ethiopian newborns using air displacement plethysmography (ADP). Female gender and being an infant of primi- or secundiparous mothers predicted lower BW and lower birth FFM but not FM, compared with male gender and infants of multiparous mothers, respectively. There was a positive linear relationship...

Neural specialization for hovering in hummingbirds: hypertrophy of the pretectal nucleus Lentiformis mesencephali.

Science.gov (United States)

Iwaniuk, Andrew N; Wylie, Douglas R W

2007-01-10

Hummingbirds possess an array of morphological and physiological specializations that allow them hover such that they maintain a stable position in space for extended periods. Among birds, this sustained hovering is unique to hummingbirds, but possible neural specializations underlying this behavior have not been investigated. The optokinetic response (OKR) is one of several behaviors that facilitates stabilization. In birds, the OKR is generated by the nucleus of the basal optic root (nBOR) and pretectal nucleus lentiformis mesencephali (LM). Because stabilization during hovering is dependent on the OKR, we predicted that nBOR and LM would be significantly enlarged in hummingbirds. We examined the relative size of nBOR, LM, and other visual nuclei of 37 species of birds from 13 orders, including nine hummingbird species. Also included were three species that hover for short periods of time (transient hoverers; a kingfisher, a kestrel, and a nectarivorous songbird). Our results demonstrate that, relative to brain volume, LM is significantly hypertrophied in hummingbirds compared with other birds. In the transient hoverers, there is a moderate enlargement of the LM, but not to the extent found in the hummingbirds. The same degree of hypertrophy is not, however, present in nBOR or the other visual nuclei measured: nucleus geniculatus lateralis, pars ventralis, and optic tectum. This selective hypertrophy of LM and not other visual nuclei suggests that the direction-selective optokinetic neurons in LM are critical for sustained hovering flight because of their prominent role in the OKR and gaze stabilization. (c) 2006 Wiley-Liss, Inc.

Muscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy

OpenAIRE

Mitchell, Cameron J.; Churchward-Venne, Tyler A.; Bellamy, Leeann; Parise, Gianni; Baker, Steven K.; Phillips, Stuart M.

2013-01-01

PURPOSE: To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH), insulin like grow factor 1 (IGF-1) and interleukin 6 (IL-6)], or intramuscular [skeletal muscle androgen receptor (AR) protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. METHODS: Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk....

Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

Science.gov (United States)

2014-01-01

Background Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats. Methods Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days. Results Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4. Conclusions Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats. PMID:24521405

Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

Science.gov (United States)

Zhang, M-J; Gu, Y; Wang, H; Zhu, P-F; Liu, X-Y; Wu, J

2016-01-01

Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

Body fat and fat-free mass and all-cause mortality

DEFF Research Database (Denmark)

Bigaard, Janne; Frederiksen, Kirsten; Tjønneland, Anne

2004-01-01

OBJECTIVE: To investigate whether the association between BMI and all-cause mortality could be disentangled into opposite effects of body fat and fat-free mass (FFM). RESEARCH METHODS AND PROCEDURES: All-cause mortality was studied in the Danish follow-up study "Diet, Cancer and Health" with 27...... fat mass divided by height squared), FFM index (FFM divided by height squared), and mortality. All analyses were adjusted for smoking habits. RESULTS: Men and women showed similar associations. J-shaped associations were found between body fat mass index and mortality adjusted for FFM and smoking....... The mortality rate ratios in the upper part of body fat mass were 1.12 per kg/m2 (95% confidence interval: 1.07, 1.18) in men and 1.06 per kg/m2 (95% confidence interval: 1.02, 1.10) in women. Reversed J-shaped associations were found between FFM index and mortality with a tendency to level off for high values...

Role of cyclic AMP sensor Epac1 in masseter muscle hypertrophy and myosin heavy chain transition induced by β2-adrenoceptor stimulation.

Science.gov (United States)

Ohnuki, Yoshiki; Umeki, Daisuke; Mototani, Yasumasa; Jin, Huiling; Cai, Wenqian; Shiozawa, Kouichi; Suita, Kenji; Saeki, Yasutake; Fujita, Takayuki; Ishikawa, Yoshihiro; Okumura, Satoshi

2014-12-15

The predominant isoform of β-adrenoceptor (β-AR) in skeletal muscle is β2-AR and that in the cardiac muscle is β1-AR. We have reported that Epac1 (exchange protein directly activated by cAMP 1), a new protein kinase A-independent cAMP sensor, does not affect cardiac hypertrophy in response to pressure overload or chronic isoproterenol (isoprenaline) infusion. However, the role of Epac1 in skeletal muscle hypertrophy remains poorly understood. We thus examined the effect of disruption of Epac1, the major Epac isoform in skeletal muscle, on masseter muscle hypertrophy induced by chronic β2-AR stimulation with clenbuterol (CB) in Epac1-null mice (Epac1KO). The masseter muscle weight/tibial length ratio was similar in wild-type (WT) and Epac1KO at baseline and was significantly increased in WT after CB infusion, but this increase was suppressed in Epac1KO. CB treatment significantly increased the proportion of myosin heavy chain (MHC) IIb at the expense of that of MHC IId/x in both WT and Epac1KO, indicating that Epac1 did not mediate the CB-induced MHC isoform transition towards the faster isoform. The mechanism of suppression of CB-mediated hypertrophy in Epac1KO is considered to involve decreased activation of Akt signalling. In addition, CB-induced histone deacetylase 4 (HDAC4) phosphorylation on serine 246 mediated by calmodulin kinase II (CaMKII), which plays a role in skeletal muscle hypertrophy, was suppressed in Epac1KO. Our findings suggest that Epac1 plays a role in β2-AR-mediated masseter muscle hypertrophy, probably through activation of both Akt signalling and CaMKII/HDAC4 signalling. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Fat utilization during exercise

DEFF Research Database (Denmark)

Helge, Jørn Wulff; Watt, Peter W.; Richter, Erik

2001-01-01

1. This study was carried out to test the hypothesis that the greater fat oxidation observed during exercise after adaptation to a high-fat diet is due to an increased uptake of fat originating from the bloodstream. 2. Of 13 male untrained subjects, seven consumed a fat-rich diet (62 % fat, 21...... % carbohydrate) and six consumed a carbohydrate-rich diet (20 % fat, 65 % carbohydrate). After 7 weeks of training and diet, 60 min of bicycle exercise was performed at 68 +/- 1 % of maximum oxygen uptake. During exercise [1-(13)C]palmitate was infused, arterial and venous femoral blood samples were collected......, and blood flow was determined by the thermodilution technique. Muscle biopsy samples were taken from the vastus lateralis muscle before and after exercise. 3. During exercise, the respiratory exchange ratio was significantly lower in subjects consuming the fat-rich diet (0.86 +/- 0.01, mean +/- S.E.M.) than...

[Molecular mechanisms of skeletal muscle hypertrophy].

Science.gov (United States)

Astratenkova, I V; Rogozkin, V A

2014-06-01

Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

[Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy].

Science.gov (United States)

Wang, Hegui; Huang, Ting; Wang, Zheng; Ge, Nannan; Ke, Yongsheng

2018-04-28

To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.
 Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (Pguinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.
 Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation 
of IKs.

Recurrent parotid swelling secondary to masseter muscle hypertrophy: a multidisciplinary diagnostic and therapeutic approach.

Science.gov (United States)

Capaccio, Pasquale; Gaffuri, Michele; Pignataro, Lorenzo; Assandri, Fausto; Pereira, Pollyanna; Farronato, Giampietro

2016-11-01

To present a patient with an atypical recurrent parotid swelling due to masseter muscle hypertrophy and the diagnostic/therapeutic assessment to treat this condition. A patient referring recurrent right facial swelling underwent a complete multidisciplinary assessment of the parotid region that revealed masseter muscle hypertrophy, confirmed by means of clinical (otolaryngological and gnathological evaluation), radiological (utrasonography, dynamic magnetic resonance imaging, and cone beam computed tomography), instrumental (electromyography to evaluate the right masseter muscle function and kinesiography to evaluate maximum right deflection - MaxRDefl and maximum opening - MaxMO) and sialendoscopy assessment where T0 indicates the pre-treatment values. All electromyographic and kinesiographic parameters were evaluated six months after the orthodontic application of a neuromuscular orthosis at T1. At T1, the effectiveness of the orthodontic therapy was demonstrated by the complete resolution of symptoms, and instrumental results documented more efficient muscle activity at rest and during clenching and a better mandibular position. At EMG T1, the resting and post-TENS values were, respectively, 1.2 and 1.8 microV. At kinesiography, MaxRDefl increased from 10.2 (T0) to 10.5 mm (T1); maxMO increased from 41.2 (T0) to 48 mm (T1). The proposed multidisciplinary assessment based on otolaryngological, gnathological, and radiological evaluation may be useful in the case of recurrent parotid swelling secondary to masseter muscle hypertrophy to plan an appropriate management with a removable neuromuscular orthosis.

Chronic low-level arsenite exposure through drinking water increases blood pressure and promotes concentric left ventricular hypertrophy in female mice.

Science.gov (United States)

Sanchez-Soria, Pablo; Broka, Derrick; Monks, Sarah L; Camenisch, Todd D

2012-04-01

Cardiovascular disease is the leading cause of death in the United States and worldwide. High incidence of cardiovascular diseases has been linked to populations with elevated arsenic content in their drinking water. Although this correlation has been established in many epidemiological studies, a lack of experimental models to study mechanisms of arsenic-related cardiovascular pathogenesis has limited our understanding of how arsenic exposure predisposes for development of hypertension and increased cardiovascular mortality. Our studies show that mice chronically exposed to drinking water containing 100 parts per billion (ppb) sodium arsenite for 22 weeks show an increase in both systolic and diastolic blood pressure. Echocardiographic analyses as well as histological assessment show concentric left ventricular hypertrophy, a primary cardiac manifestation of chronic hypertension. Live imaging by echocardiography shows a 43% increase in left ventricular mass in arsenic-treated animals. Relative wall thickness (RWT) was calculated showing that all the arsenic-exposed animals show an RWT greater than 0.45, indicating concentric hypertrophy. Importantly, left ventricular hypertrophy, although often associated with chronic hypertension, is an independent risk factor for cardiovascular-related mortalities. These results suggest that chronic low-level arsenite exposure promotes the development of hypertension and the comorbidity of concentric hypertrophy.

Comparison of fat maintenance in the face with centrifuge versus filtered and washed fat.

Science.gov (United States)

Asilian, Ali; Siadat, Amir Hossein; Iraji, Razieh

2014-06-01

Autogenous fat injection of the face is a viable and lasting remedy for soft tissue loss and has become a mainstay in facial rejuvenation. Fat transfer as either a stand-alone technique or as an adjunct to other filler technique and lifting depending on patient needs. Although soft tissue augmentation with autologous fat transfer has been increasingly used by esthetic surgeon, but there is no agreement concerning the best way of processing the harvested fat before injection. This study compared the clinical results obtained using simple filtered and washed fat via metal sieve with those achieved by means of pure centrifuged fat. A prospective single-blind analysis on 32 healthy patients undergoing nasolabial fold fat transplantation from 2009 to 2011 (simple sampling). Patients assigned in two groups randomly. The face of half (16 subjects) was injected with centrifuged, another half with simple filtered and washed fat to evaluate the effect of preparation methods on fat graft viability. Objective method was used to evaluate the results, involving the evaluation of postoperative photographs (in month 1, 6 and 12) by an esthetic surgeon (according to the nasolabial scale). Subjective method was a self-assessment obtained from patients about general level of satisfaction and improvement of skin texture, statistical analysis were performed by means of the Wilcoxon and Mann-Whitney test. Acquired data were analyzed using SPSS version 15 and a value of P > 0.05 was considered as significant. There was no significant difference in the survival of grafted fat between the Group 1 (fat-processing with centrifuge at 3400 rpm for 1-min) and Group 2 (washing the fat in the sieve). Our data suggest that the centrifuge of the fat does not enhance survival of grafted fat (P > 0.05).

Impact of fasting glucose on electrocardiographic left ventricular hypertrophy in an elderly general population

DEFF Research Database (Denmark)

Diederichsen, Søren Z; Pareek, Manan; Nielsen, Mette L

2015-01-01

OBJECTIVE: To evaluate relationships between fasting plasma glucose (FPG), other cardiovascular risk markers and left ventricular hypertrophy (LVH) as detected by electrocardiography. METHODS: Subjects were selected randomly from groups defined by FPG. Traditional risk markers were assessed. LVH...

Masseter Muscle Hypertrophy and Pericardial Effusion in Kocher-Debre-Semelaigne Syndrome Child

Directory of Open Access Journals (Sweden)

Taksande AM

2015-10-01

Full Text Available Muscular pseudohypertrophy associated with severe congenital hypothyroidism has been described as Kocher Debre Semelaigne syndrome, which is a rare disorder. We report a case of 9year old female child with hypothyroidism, limb muscular pseudo-hypertrophy with involvement of masseter muscle along with pericardial effusion in Kocher-Debré-Semelaigne syndrome.

PANCREATIC HYPERTROPHY IN RATS CAUSED BY CHICKPEA (Cicer arietinum L. PROTEIN INTAKE

Directory of Open Access Journals (Sweden)

O. L. TAVANO

2008-10-01

Full Text Available

The objectives of this work were demonstrate the occurrence of pancreatic hypertrophy in rats, caused by chickpea protein intake, and the possible relation to the presence of trypsin inhibitors in the protein samples. The principal protein fractions of chickpea were isolated, the effect of heating was also tested (121°C/15 min. The heated chickpea diets did not cause significant pancreatic hypertrophy in rats, in relation to the casein control group. Only unheated chickpea flour and albumin diets caused pancreatic weight increases correlating to the presence of trypsin inhibitors in these samples. Apart from the trypsin inhibitor activity the other chickpea protein components appear not to exert any alteration in pancreatic weight.

Electrocardiographic left ventricular hypertrophy without echocardiographic abnormalities evaluated by myocardial perfusion and fatty acid metabolic imaging

International Nuclear Information System (INIS)

Narita, Michihiro; Kurihara, Tadashi

2000-01-01

The pathophysiologic process in patients with electrocardiographic left ventricular hypertrophy with ST, T changes but without echocardiographic abnormalities was investigated by myocardial perfusion imaging and fatty acid metabolic imaging. Exercise stress 99m Tc-methoxy-isobutyl isonitrile (MIBI) imaging and rest 123 I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) imaging were performed in 59 patients with electrocardiographic hypertrophy including 29 without apparent cause including hypertension and echocardiographic hypertrophy, and 30 with essential hypertension. Coronary angiography was performed in 6 patients without hypertension and 4 with hypertension and biopsy specimens were obtained from the left ventricular apex from 6 patients without hypertension. Myocardial perfusion and 123 I-BMIPP images were classified into 3 types: normal, increased accumulation of the isotope at the left ventricular apex (high uptake) and defect. Transient perfusion abnormality and apical defect observed by 123 I-BMIPP imaging were more frequent in patients without hypertension than in patients with hypertension (32% vs. 17%, p=0.04671 in perfusion; 62% vs. 30%, p=0.0236 in 123 I-BMIPP). Eighteen normotensive patients with apical defect by 123 I-BMIPP imaging included 3 of 10 patients with normal perfusion at exercise, 6 of 10 patients with high uptake and 9 of 9 patients with perfusion defect. The defect size revealed by 123 I-BMIPP imaging was greater than that of the perfusion abnormality. Coronary stenoses were not observed and myocardial specimens showed myocardial disarray with hypertrophy. Moreover, 9 patients with hypertension and apical defects by 123 I-BMIPP showed 3 different types of perfusion. Many patients without hypertension show a pathologic process similar to hypertrophic cardiomyopathy. Perfusion and 123 I-BMIPP imaging are useful for the identification of these patients. (author)

[Effectiveness of the GlideScope video laryngoscope in a case of unexpected difficult airway due to lingual tonsil hypertrophy].

Science.gov (United States)

Cruz, P; Alarcón, L; Del Castillo, T; Cabrerizo, P; Díaz, S

2015-05-01

Lingual tonsil hypertrophy can cause varying degrees of airway obstruction and is considered a risk factor for difficult mask ventilation and tracheal intubation. We report a case of unexpected difficult airway in a patient with unknown lingual tonsil hypertrophy that was solved with the use of the GlideScope video laryngoscope. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy.

Science.gov (United States)

Fry, Christopher S; Kirby, Tyler J; Kosmac, Kate; McCarthy, John J; Peterson, Charlotte A

2017-01-05

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation. Copyright © 2017 Elsevier Inc. All rights reserved.

The relationship of enuresis nocturna and adenoid hypertrophy

Directory of Open Access Journals (Sweden)

Muhsin Balaban

2016-07-01

Full Text Available Objectives: This study was organized to assess the relationship of enuresis nocturna (EN and upper airway obstruction (UAO in children. Material and Methods: This study was multi-centrically and prospectively designed including 79 children who presented to a urology clinic with symptoms of EN between January 2013 and February 2014. Sixty-four age-matched children with no history of urological complaints were randomly recruited from children admitted to a pediatric clinic as a control group. All children and parents were asked to fill out a dysfunctional elimination syndrome (DES questionnaire and children were examined by an ear, nose and throat (ENT specialist to evaluate the UAO. Descriptive statistics, chisquare and Mann-Whitney-U tests were used to compare variables. Results: The mean ages of the 79 children (48 male, 31 female in the study group and the 64 children (41 male, 23 female in the control group were 10.14+/-3.38 and 9.17+/- 2.85, respectively. Family history of the study showed that 19% of the children’s mothers, 10% of the children’s fathers and 37% of the children’s siblings had experienced EN. There was a significant difference between the study and the control groups in terms of urge to urinate, bladder emptying, bowel symptoms and psychological stress. There was also a significant difference between rates of tonsillar hypertrophy and nasopharynx obstruction in the EN group (p = 0.009. Conclusion: In this study we found that half of the children with EN had tonsillar hypertrophy, which was significantly higher than in the control group. Further studies are needed to clarify the exact relationship between UAO and EN.

Fat heaps

DEFF Research Database (Denmark)

Elmasry, Amr Ahmed Abd Elmoneim; Katajainen, Jyrki

This report is an electronic appendix to our paper \\Fat heaps without regular counters". In that paper we described a new variant of fat heaps that is conceptually simpler and easier to implement than the original version. We also compared the practical performance of this data structure...

CASE REPORT Macrodystrophia lipomatosa – MR imaging of a rare ...

African Journals Online (AJOL)

This rare congenital abnormality occurs most frequently in the .... 1st, 2nd and 3rd digits owing to gross hypertrophy of fat and soft tissue in a striated pattern. ... a part of generalised hamartomatous disorder featuring fat in the soft tissues and ...

Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Czech Academy of Sciences Publication Activity Database

McDermott-Roe, Ch.; Ye, J.; Ahmed, R.; Sun, X. M.; Serafín, A.; Ware, J.; Bottolo, L.; Muckett, P.; Caňas, X.; Zhang, J.; Rowe, G. C.; Buchan, R.; Lu, H.; Braithwaite, A.; Mancini, M.; Hauton, D.; Martí, R.; García-Arumí, E.; Hubner, N.; Jacob, H.; Serikawa, T.; Zídek, Václav; Papoušek, František; Kolář, František; Cardona, M.; Ruiz-Meana, M.; García-Dorado, D.; Comella, J. X.; Felkin, L. E.; Barton, P. J. R.; Arany, Z.; Pravenec, Michal; Petretto, E.; Sanchis, D.; Cook, S.A.

2011-01-01

Roč. 478, č. 7367 (2011), s. 114-118 ISSN 0028-0836 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA301/08/0166 Institutional research plan: CEZ:AV0Z50110509 Keywords : left ventricular hypertrophy * endonuclease G * mitochondrial dysfunction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 36.280, year: 2011

The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

NARCIS (Netherlands)

Zhong, Leilei; Huang, X; Karperien, Hermanus Bernardus Johannes; Post, Janine Nicole

2015-01-01

Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the

Basic models modeling resistance training: an update for basic scientists interested in study skeletal muscle hypertrophy.

Science.gov (United States)

Cholewa, Jason; Guimarães-Ferreira, Lucas; da Silva Teixeira, Tamiris; Naimo, Marshall Alan; Zhi, Xia; de Sá, Rafaele Bis Dal Ponte; Lodetti, Alice; Cardozo, Mayara Quadros; Zanchi, Nelo Eidy

2014-09-01

Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints. © 2013 Wiley Periodicals, Inc.

Korean mistletoe (Viscum album coloratum) extract regulates gene expression related to muscle atrophy and muscle hypertrophy.

Science.gov (United States)

Jeong, Juseong; Park, Choon-Ho; Kim, Inbo; Kim, Young-Ho; Yoon, Jae-Min; Kim, Kwang-Soo; Kim, Jong-Bae

2017-01-21

Korean mistletoe (Viscum album coloratum) is a semi-parasitic plant that grows on various trees and has a diverse range of effects on biological functions, being implicated in having anti-tumor, immunostimulatory, anti-diabetic, and anti-obesity properties. Recently, we also reported that Korean mistletoe extract (KME) improves endurance exercise in mice, suggesting its beneficial roles in enhancing the capacity of skeletal muscle. We examined the expression pattern of several genes concerned with muscle physiology in C2C12 myotubes cells to identify whether KME inhibits muscle atrophy or promotes muscle hypertrophy. We also investigated these effects of KME in denervated mice model. Interestingly, KME induced the mRNA expression of SREBP-1c, PGC-1α, and GLUT4, known positive regulators of muscle hypertrophy, in C2C12 cells. On the contrary, KME reduced the expression of Atrogin-1, which is directly involved in the induction of muscle atrophy. In animal models, KME mitigated the decrease of muscle weight in denervated mice. The expression of Atrogin-1 was also diminished in those mice. Moreover, KME enhanced the grip strength and muscle weight in long-term feeding mice. Our results suggest that KME has beneficial effects on muscle atrophy and muscle hypertrophy.

Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats.

Science.gov (United States)

Zhu, Zeng-Yan; Gao, Tian; Huang, Yan; Xue, Jie; Xie, Mei-Lin

2016-04-01

Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4.

IGF-II is up-regulated and myofibres are hypertrophied in regenerating soleus of mice lacking FGF6

International Nuclear Information System (INIS)

Armand, Anne-Sophie; Lecolle, Sylvie; Launay, Thierry; Pariset, Claude; Fiore, Frederic; Della Gaspera, Bruno; Birnbaum, Daniel; Chanoine, Christophe; Charbonnier, Frederic

2004-01-01

Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the use of FGF6(-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remains largely unclear. Using FGF6(-/-) mice, we first analysed the morphology of the regenerated soleus following cardiotoxin injection and showed hypertrophied myofibres in soleus of the mutant mice as compared to wild-type mice. Secondly, to examine the function of the IGF family in the hypertrophy process, we used semiquantitative and real-time RT-PCR assays and Western blots to monitor the expression of the insulin-like growth factors (IGF-I and IGF-II), their receptors [type I IGF receptor (IGF1R) and IGF-II receptor (IGF2R)], and of a binding protein IGFBP-5 in regenerating soleus muscles of FGF6(-/-) knockout mice vs. wild-type mice. In the mutant, both IGF-II and IGF2R, but not IGF-I and IGF1R, were strongly up-regulated, whereas IGFBP5 was down-regulated, strongly suggesting that, in the absence of FGF6, the mechanisms leading to myofibre hypertrophy were mediated specifically by an IGF-II/IGF2R signalling pathway distinct from the classic mechanism involving IGF-I and IGF1R previously described for skeletal muscle hypertrophy. The potential regulating role of IGFBP5 on IGF-II expression is also discussed. This report shows for the first time a specific role for FGF6 in the regulation of myofibre size during a process of in vivo myogenesis

Compensatory hypertrophy of the teres minor muscle after large rotator cuff tear model in adult male rat.

Science.gov (United States)

Ichinose, Tsuyoshi; Yamamoto, Atsushi; Kobayashi, Tsutomu; Shitara, Hitoshi; Shimoyama, Daisuke; Iizuka, Haku; Koibuchi, Noriyuki; Takagishi, Kenji

2016-02-01

Rotator cuff tear (RCT) is a common musculoskeletal disorder in the elderly. The large RCT is often irreparable due to the retraction and degeneration of the rotator cuff muscle. The integrity of the teres minor (TM) muscle is thought to affect postoperative functional recovery in some surgical treatments. Hypertrophy of the TM is found in some patients with large RCTs; however, the process underlying this hypertrophy is still unclear. The objective of this study was to determine if compensatory hypertrophy of the TM muscle occurs in a large RCT rat model. Twelve Wistar rats underwent transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons in the left shoulder. The rats were euthanized 4 weeks after the surgery, and the cuff muscles were collected and weighed. The cross-sectional area and the involvement of Akt/mammalian target of rapamycin (mTOR) signaling were examined in the remaining TM muscle. The weight and cross-sectional area of the TM muscle was higher in the operated-on side than in the control side. The phosphorylated Akt/Akt protein ratio was not significantly different between these sides. The phosphorylated-mTOR/mTOR protein ratio was significantly higher on the operated-on side. Transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons activates mTOR signaling in the TM muscle, which results in muscle hypertrophy. The Akt-signaling pathway may not be involved in this process. Nevertheless, activation of mTOR signaling in the TM muscle after RCT may be an effective therapeutic target of a large RCT. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

Science.gov (United States)

Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

2012-01-01

African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats

NARCIS (Netherlands)

Tian, Xiao-Li; Pinto, Yigal Martin; Costerousse, Olivier; Franz, Wolfgang M.; Lippoldt, Andrea; Hoffmann, Sigrid; Unger, Thomas; Paul, Martin

2004-01-01

Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains

Appearance of high signal intensity and gadolinium-DTPA contrast enhancement in hypertrophied myocardium by magnetic resonance imaging

International Nuclear Information System (INIS)

Nishimura, Tsunehiko; Yamada, Naoaki; Nagata, Seiki

1989-01-01

This study was undertaken to examine the potential role of magnetic resonance imaging (MRI) for evaluating myocardial tissue characterization in hypertrophic cardiomyopathy (HCM). ECG-gated MRI images were acquired in 32 HCM patients and 30 patients with hypertensive heart disease (HHD), using a 1.5 T superconducting magnet system. The thickened areas were depicted as high signal intensities in the septum of 12 HCM patients (38%) and the endocardium of 5 HHD patients (17%). Echocardiography revealed that MRI appearance of high signal intensity was associated with more thickened myocardial wall. For evaluable 16 patients receiving i.v. injection of Gd-DTPA in a dose of 0.1 mM/kg, enhancement effects were observed in 10 patients (63%). High signal intensity appearing in the hypertrophied myocardium, as well as contrast enhancement, may not be characteristic of HCM, but reflect the likelihood of myocardial degeneration associated with the hypertrophied myocardium. Although MRI may not be capable of differentiating tissue characterization in HCM from that in HHD, it may provide different information about tissue characterization in the hypertrophied myocardium from that obtained by other techniques. (N.K.)

Muscular hypertrophy and atrophy in normal rats provoked by the administration of normal and denervated muscle extracts.

Science.gov (United States)

Agüera, Eduardo; Castilla, Salvador; Luque, Evelio; Jimena, Ignacio; Leiva-Cepas, Fernando; Ruz-Caracuel, Ignacio; Peña, José

2016-12-01

This study was conducted to determine the effects of extracts obtained from both normal and denervated muscles on different muscle types. Wistar rats were used and were divided into a control group and four experimental groups. Each experimental group was treated intraperitoneally during 10 consecutive days with a different extract. These extracts were obtained from normal soleus muscle, denervated soleus, normal extensor digitorum longus, and denervated extensor digitorum longus. Following treatment, the soleus and extensor digitorum longus muscles were obtained for study under optic and transmission electron microscope; morphometric parameters and myogenic responses were also analyzed. The results demonstrated that the treatment with normal soleus muscle and denervated soleus muscle extracts provoked hypertrophy and increased myogenic activity. In contrast, treatment with extracts from the normal and denervated EDL had a different effect depending on the muscle analyzed. In the soleus muscle it provoked hypertrophy of type I fibers and increased myogenic activity, while in the extensor digitorum longus atrophy of the type II fibers was observed without changes in myogenic activity. This suggests that the muscular responses of atrophy and hypertrophy may depend on different factors related to the muscle type which could be related to innervation.

Influence of hypertensive left ventricular hypertrophy on detection of ischemic area with exercise thallium-201 myocardial scintigraphy

International Nuclear Information System (INIS)

Toyama, Takuji; Nishimura, Tsunehiko; Uehara, Toshiisa

1992-01-01

Sixty-four patients with single left anterior descending artery disease having effort angina (group A: 40 patients with hypertrophic hypertension, group B: 10 patients with hypertrophic hypertension, group C: 14 patients with non-hypertrophic hypertension) were assessed to determine the influence of hypertensive left ventricular (LV) hypertrophy on detection of ischemic area. The criterion of hypertrophy by two-dimensional echocardiography was >12 mm in the wall thickness of interventricular septal or posterior wall. Population in Group B might show low detectability in ischemic area by 201 Tl myocardial scintigraphy (positive thallium rate 60%, defect score 2.7±3.6), and high lung thallium uptake and high frequence of ECG positive among three groups. In semiquantitative analysis, the washout rate of the posterolateral wall and %RD (delayed %uptake-initial %uptake) of the septal wall in patients with Group B were lowest among three groups. However, the washout rate in the septal wall against the posterior wall, and the initial %uptake and the delayed %uptake of the septal wall were not significantly different among three groups. We could conclude that the decreased washout rate in nonischemic area with hypertensive LV hypertrophy might make the ischemic area masked. (author)

Enzymatically modified isoquercitrin supplementation intensifies plantaris muscle fiber hypertrophy in functionally overloaded mice.

Science.gov (United States)

Kohara, Akiko; Machida, Masanao; Setoguchi, Yuko; Ito, Ryouichi; Sugitani, Masanori; Maruki-Uchida, Hiroko; Inagaki, Hiroyuki; Ito, Tatsuhiko; Omi, Naomi; Takemasa, Tohru

2017-01-01

Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.

Detection of non-milk fat in milk fat by gas chromatography and linear discriminant analysis.

Science.gov (United States)

Gutiérrez, R; Vega, S; Díaz, G; Sánchez, J; Coronado, M; Ramírez, A; Pérez, J; González, M; Schettino, B

2009-05-01

Gas chromatography was utilized to determine triacylglycerol profiles in milk and non-milk fat. The values of triacylglycerol were subjected to linear discriminant analysis to detect and quantify non-milk fat in milk fat. Two groups of milk fat were analyzed: A) raw milk fat from the central region of Mexico (n = 216) and B) ultrapasteurized milk fat from 3 industries (n = 36), as well as pork lard (n = 2), bovine tallow (n = 2), fish oil (n = 2), peanut (n = 2), corn (n = 2), olive (n = 2), and soy (n = 2). The samples of raw milk fat were adulterated with non-milk fats in proportions of 0, 5, 10, 15, and 20% to form 5 groups. The first function obtained from the linear discriminant analysis allowed the correct classification of 94.4% of the samples with levels <10% of adulteration. The triacylglycerol values of the ultrapasteurized milk fats were evaluated with the discriminant function, demonstrating that one industry added non-milk fat to its product in 80% of the samples analyzed.

The left atrium, atrial fibrillation, and the risk of stroke in hypertensive patients with left ventricular hypertrophy

DEFF Research Database (Denmark)

Wachtell, K.; Devereux, R.B.; Lyle, P.A.

2008-01-01

was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV......The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study provided extensive data on predisposing factors, consequences, and prevention of atrial fibrillation (AF) in patients with hypertension and left ventricular (LV) hypertrophy. Randomized losartan-based treatment...... hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease Udgivelsesdato: 2008/12...

Deep intronic mutation and pseudo exon activation as a novel muscular hypertrophy modifier in cattle.

Directory of Open Access Journals (Sweden)

Claire Bouyer

Full Text Available Myostatin is essential for proper regulation of myogenesis, and inactivation of Myostatin results in muscle hypertrophy. Here, we identified an unexpected mutation in the myostatin gene which is almost fixed in Blonde d'Aquitaine cattle. In skeletal muscle, the mutant allele was highly expressed leading to an abnormal transcript consisting of a 41-bp inclusion and premature termination codons and to residual levels of a correctly spliced transcript. This expression pattern, caused by a leaky intronic mutation with regard to spliceosome activity and its apparent stability with regard to surveillance mechanisms, could contribute to the moderate muscle hypertrophy in this cattle breed. This finding is of importance for genetic counseling for meat quantity and quality in livestock production and possibly to manipulate myostatin pre-mRNA in human muscle diseases.

Effects of contraction mode and stimulation frequency on electrical stimulation-induced skeletal muscle hypertrophy.

Science.gov (United States)

Ashida, Yuki; Himori, Koichi; Tatebayashi, Daisuke; Yamada, Ryotaro; Ogasawara, Riki; Yamada, Takashi

2018-02-01

We compared the skeletal muscle hypertrophy resulting from isometric (Iso) or eccentric (Ecc) electrical stimulation (ES) training with different stimulation frequencies. Male Wistar rats were assigned to the Iso and Ecc groups. These were divided into three further subgroups that were stimulated at 10 Hz (Iso-10 and Ecc-10), 30 Hz (Iso-30 and Ecc-30), or 100 Hz (Iso-100 and Ecc-100). In experiment 1, the left plantarflexor muscles were stimulated every other day for 3 wk. In experiment 2, mammalian target of rapamycin complex 1 (mTORC1) signaling was investigated 6 h after one bout of ES. The contralateral right muscle served as a control (non-ES). Ecc contractions comprised forced dorsiflexion combined with ES. The peak torque and torque-time integral during ES were higher in the Ecc group than that in the Iso group in all stimulation frequencies examined. The gastrocnemius muscle weight normalized to body weight in ES side was increased compared with the non-ES side by 6, 7, and 17% in the Ecc-30, Iso-100, and Ecc-100 groups, respectively, with a greater gain in Ecc-100 than the Ecc-30 and Iso-100 groups. The p70S6K (Thr389) phosphorylation level was higher in the Ecc-30 and -100 than in the Iso-30 and -100 groups, respectively. The peak torque and torque-time integral were highly correlated with the magnitude of increase in muscle mass and the phosphorylation of p70S6K. These data suggest that ES-induced muscle hypertrophy and mTORC1 activity are determined by loading intensity and volume during muscle contraction independent of the contraction mode. NEW & NOTEWORTHY Eccentric contraction and high-frequency stimulation (HFS) are regarded as an effective way to increase muscle mass by electrical stimulation (ES) training. However, little is known about whether muscle hypertrophy is affected by contraction mode and stimulation frequency in ES training. Here, we provide the evidence that muscle hypertrophy and mammalian target of rapamycin complex 1 activity are

Low-fat vs. high-fat bedtime snacks in children and adolescents with type 1 diabetes.

Science.gov (United States)

Wilson, Darrell; Chase, H Peter; Kollman, Craig; Xing, Dongyuan; Caswell, Kimberly; Tansey, Michael; Fox, Larry; Weinzimer, Stuart; Beck, Roy; Ruedy, Katrina; Tamborlane, William

2008-07-28

The purpose of this study was to determine whether, in a group of children with type 1 diabetes using insulin pump, a prebedtime snack with a relatively high fat content provides greater protection from nocturnal hypoglycemia than a snack containing the same amount of carbohydrate and protein but a lower fat content. Ten subjects, aged 6 to carbohydrate-low-fat (30 g CHO, 2.5 g protein, and 1.3 g fat; 138 kcal) snack or a carbohydrate-high-fat (30 g CHO, 2 g protein, and 20 g fat; 320 kcal) snack. Subjects used their usual evening snack algorithm to determine the size (in 15-g carbohydrate increments) and insulin dosage. Average glucose on 128 valid study nights before snack was similar in both groups. The proportion of nights with hypoglycemia (a sensor or meter glucose value fat vs. 20% low fat), as was the proportion of nights with hyperglycemia (a glucose >or=200 mg/dL and at least 50 mg/dL above baseline, 35% high fat vs. 30% low fat). There were no statistical differences between the high- and low-fat snacks on the frequency of hyperglycemia or hypoglycemia. This study highlights the feasibility of web-based research in patients' home environment.

Psoriasis is associated with subsequent atrial fibrillation in hypertensive patients with left ventricular hypertrophy

DEFF Research Database (Denmark)

Bang, Casper N; Okin, Peter M; Køber, Lars

2014-01-01

BACKGROUND: Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation. The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: The predictive value...... or developed psoriasis and new-onset atrial fibrillation occurred in 506 patients (7.1%) during a mean follow-up of 4.7 ± 1.1 years. At baseline, the psoriasis patients were younger (65 ± 7 vs. 67 ± 7 years) and had less left ventricle hypertrophy by ECG Sokolow-Lyon voltage (27.6 ± 9.7 vs. 30.1 ± 10.4 mm...... of baseline or incident psoriasis for new-onset atrial fibrillation was evaluated in 7099 hypertensive patients with electrocardiographic LVH with no history of atrial fibrillation or other cardiovascular disease, in sinus rhythm on their baseline electrocardiogram. RESULTS: A total of 154 patients (2.2%) had...

Body fat, abdominal fat and body fat distribution related to VO(2PEAK) in young children

DEFF Research Database (Denmark)

Dencker, Magnus; Wollmer, Per; Karlsson, Magnus K

2011-01-01

as a percentage of body mass (BF%) and body fat distribution as AFM/TBF. VO(2PEAK) was assessed by indirect calorimetry during maximal exercise test. Results. Significant relationships existed between body fat measurements and VO(2PEAK) in both boys and girls, with Pearson correlation coefficients for absolute...

Relationships between rodent white adipose fat pads and human white adipose fat depots

Directory of Open Access Journals (Sweden)

Daniella E. Chusyd

2016-04-01

Full Text Available The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of white adipose tissue. Thus, further research is warranted to more carefully define the strengths and limitations of rodent white adipose tissue as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat.

Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

Science.gov (United States)

Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

2016-01-01

Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet.

Science.gov (United States)

Kabisch, Stefan; Bäther, Sabrina; Dambeck, Ulrike; Kemper, Margrit; Gerbracht, Christiana; Honsek, Caroline; Sachno, Anna; Pfeiffer, Andreas F H

2018-01-31

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder all over the world, mainly being associated with a sedentary lifestyle, adiposity, and nutrient imbalance. The increasing prevalence of NAFLD accommodates similar developments for type 2 diabetes and diabetes-related comorbidities and complications. Therefore, early detection of NAFLD is an utmost necessity. Potentially helpful tools for the prediction of NAFLD are liver fat indices. The fatty liver index (FLI) and the NAFLD-liver fat score (NAFLD-LFS) have been recently introduced for this aim. However, both indices have been shown to correlate with liver fat status, but there is neither sufficient data on the longitudinal representation of liver fat change, nor proof of a diet-independent correlation between actual liver fat change and change of index values. While few data sets on low-fat diets have been published recently, low-carb diets have not been yet assessed in this context. We aim to provide such data from a highly effective short-term intervention to reduce liver fat, comparing a low-fat and a low-carb diet in subjects with prediabetes. Anthropometric measurements, magnetic resonance (MR)-based intrahepatic lipid (IHL) content, and several serum markers for liver damage have been collected in 140 subjects, completing the diet phase in this trial. Area-under-the-responder-operator-curves (AUROC) calculations as well as cross-sectional and longitudinal Spearman correlations were used. Both FLI and NAFLD-LFS predict liver fat with moderate accuracy at baseline (AUROC 0.775-0.786). These results are supported by correlation analyses. Changes in liver fat, achieved by the dietary intervention, correlate moderately with changes in FLI and NAFLD-LFS in the low-fat diet, but not in the low-carb diet. A correlation analysis between change of actual IHL content and change of single elements of the liver fat indices revealed diet-specific moderate to strong correlations between ΔIHL and

Estrogen deprivation aggravates cardiac hypertrophy in nonobese Type 2 diabetic Goto-Kakizaki (GK) rats.

Science.gov (United States)

Apaijai, Nattayaporn; Charoenphandhu, Narattaphol; Ittichaichareon, Jitjiroj; Suntornsaratoon, Panan; Krishnamra, Nateetip; Aeimlapa, Ratchaneevan; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2017-10-31

Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) ( n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats. © 2017 The Author(s).

TISSUE POLYPEPTIDE-SPECIFIC ANTIGEN - A DISCRIMINATIVE PARAMETER BETWEEN PROSTATE-CANCER AND BENIGN PROSTATIC HYPERTROPHY

NARCIS (Netherlands)

MARRINK, J; OOSTEROM, R; BONFRER, HMG; SCHRODER, FH; MENSINK, HJA

1993-01-01

The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer

Hypertrophy in port-wine stains: Prevalence and patient characteristics in a large patient cohort

NARCIS (Netherlands)

van Drooge, Anne Margreet; Beek, Johan F.; van der Veen, J. P. Wietze; van der Horst, Chantal M. A. M.; Wolkerstorfer, Albert

2012-01-01

Background: Port-wine stains (PWS) may thicken and darken with age. Little is known about the pathogenesis and epidemiology of PWS hypertrophy because of the lack of large studies. Objective: We sought to assess the prevalence and characteristics of patients with hypertrophic PWS. Methods: Medical

Exercise intensity and muscle hypertrophy in blood flow-restricted limbs and non-restricted muscles: a brief review.

Science.gov (United States)

Abe, Takashi; Loenneke, Jeremy P; Fahs, Christopher A; Rossow, Lindy M; Thiebaud, Robert S; Bemben, Michael G

2012-07-01

Although evidence for high-intensity resistance training-induced muscle hypertrophy has accumulated over the last several decades, the basic concept of the training can be traced back to ancient Greece: Milo of Croton lifted a bull-calf daily until it was fully grown, which would be known today as progressive overload. Now, in the 21st century, different types of training are being tested and studied, such as low-intensity exercise combined with arterial as well as venous blood flow restriction (BFR) to/from the working muscles. Because BFR training requires the use of a cuff that is placed at the proximal ends of the arms and/or legs, the BFR is only applicable to limb muscles. Consequently, most previous BFR training studies have focused on the physiological adaptations of BFR limb muscles. Muscle adaptations in non-BFR muscles of the hip and trunk are lesser known. Recent studies that have reported both limb and trunk muscle adaptations following BFR exercise training suggest that low-intensity (20-30% of 1RM) resistance training combined with BFR elicits muscle hypertrophy in both BFR limb and non-BFR muscles. However, the combination of leg muscle BFR with walk training elicits muscle hypertrophy only in the BFR leg muscles. In contrast to resistance exercise with BFR, the exercise intensity may be too low during BFR walk training to cause muscle hypertrophy in the non-BFR gluteus maximus and other trunk muscles. Other mechanisms including hypoxia, local and systemic growth factors and muscle cell swelling may also potentially affect the hypertrophic response of non-BFR muscles to BFR resistance exercise. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Correlation between adenoidal nasopharyngeal ratio and symptoms of enlarged adenoids in children with adenoidal hypertrophy

Directory of Open Access Journals (Sweden)

Taiwo Olugbemiga Adedeji

2016-01-01

Full Text Available Background: Adenoid hypertrophy is one of the most common health problems affecting the paediatric population. This study aims to correlate adenoidal nasopharyngeal ratio (ANR with symptoms of enlarged adenoids in children with enlarged adenoids. Materials and Methods: It was a year, cross-sectional, hospital-based study conducted at Lautech Teaching Hospital, Osogbo. ANR was determined by dividing adenoidal depth with nasopharyngeal depth on the plain lateral radiographs. Results: A total of 90 consecutive children consisting of 61 males and 29 females were included in the study with M:F ratio of 2.1:1. Their ages ranged from 8 months to 11 years. All the patients presented with nasal obstruction, mouth breathing and noisy breathing. Majority (64.5% had severe obstructions with preponderance among children of 3-5 years (39.9%. Linear regression analysis showed significant association between age and ANR (t = 10.447, P < 0.001. There was high significant association (P < 0.05 between presenting symptoms and degree of nasopharyngeal airway obstruction; for snoring (r = 0.251, P = 0.000, sleep apnoea (r = 0.594, P = 0.000, nasal discharge (r = 0.314, P = 0.001, excessive daytime sleepiness (r = 0.219, P = 0.019 and failure to thrive (r = 0.240, P = 0.011. Conclusion: Lateral X-ray of the nasopharynx is an effective tool to evaluate children with suspected adenoid hypertrophy. It correlates well with patients′ symptoms and provides objective measures of adenoid hypertrophy.

The effect of exercise hypertrophy and disuse atrophy on muscle contractile properties: a mechanomyographic analysis.

Science.gov (United States)

Than, Christian; Tosovic, Danijel; Seidl, Laura; Mark Brown, J

2016-12-01

To determine whether mechanomyographic (MMG) determined contractile properties of the biceps brachii change during exercise-induced hypertrophy and subsequent disuse atrophy. Healthy subjects (mean ± SD, 23.7 ± 2.6 years, BMI 21.8 ± 2.4, n = 19) performed unilateral biceps curls (9 sets × 12 repetitions, 5 sessions per week) for 8 weeks (hypertrophic phase) before ceasing exercise (atrophic phase) for the following 8 weeks (non-dominant limb; treatment, dominant limb; control). MMG measures of muscle contractile properties (contraction time; T c , maximum displacement; D max , contraction velocity; V c ), electromyographic (EMG) measures of muscle fatigue (median power frequency; MPF), strength measures (maximum voluntary contraction; MVC) and measures of muscle thickness (ultrasound) were obtained. Two-way repeated measures ANOVA showed significant differences (P muscle thickness was greater than control, reflecting gross hypertrophy. MMG variables Dmax (weeks 2, 7) and Vc (weeks 7, 8) declined. During the atrophic phase, MVC (weeks 9-12) and muscle thickness (weeks 9, 10) initially remained high before declining to control levels, reflecting gross atrophy. MMG variables D max (weeks 9, 14) and V c (weeks 9, 14, 15) also declined during the atrophic phase. No change in T c was found throughout the hypertrophic or atrophic phases. MMG detects changes in contractile properties during stages of exercise-induced hypertrophy and disuse atrophy suggesting its applicability as a clinical tool in musculoskeletal rehabilitation.

Heterogeneity of capillary spacing in the hypertrophied plantaris muscle from young-adult and old rats.

NARCIS (Netherlands)

Degens, H.; Morse, C.I.; Hopman, M.T.E.

2009-01-01

Heterogeneity of capillary spacing may affect tissue oxygenation. The determinants of heterogeneity of capillary spacing are, however, unknown. To investigate whether 1) impaired angiogenesis and increased heterogeneity of capillary spacing delays development of hypertrophy during aging and 2)

"Heart rate-dependent" electrocardiographic diagnosis of left ventricular hypertrophy.

Science.gov (United States)

Madias, John E

2013-05-01

A case is presented revealing the common phenomenon of heart rate-dependent diagnosis of electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH), which consists of satisfaction of LVH criteria only at faster rates whereas ECGs with a slow heart rate do not satisfy such criteria. The mechanism of the phenomenon has been attributed to the tachycardia-mediated underfilling of the left ventricle bringing the electrical "centroid" of the heart closer to the recording electrodes, which results in augmentation of the amplitude of QRS complexes, particularly in leads V2-V4. ©2012, The Author. Journal compilation ©2012 Wiley Periodicals, Inc.

Fat ViP MRI: Virtual Phantom Magnetic Resonance Imaging of water-fat systems.

Science.gov (United States)

Salvati, Roberto; Hitti, Eric; Bellanger, Jean-Jacques; Saint-Jalmes, Hervé; Gambarota, Giulio

2016-06-01

Virtual Phantom Magnetic Resonance Imaging (ViP MRI) is a method to generate reference signals on MR images, using external radiofrequency (RF) signals. The aim of this study was to assess the feasibility of ViP MRI to generate complex-data images of phantoms mimicking water-fat systems. Various numerical phantoms with a given fat fraction, T2* and field map were designed. The k-space of numerical phantoms was converted into RF signals to generate virtual phantoms. MRI experiments were performed at 4.7T using a multi-gradient-echo sequence on virtual and physical phantoms. The data acquisition of virtual and physical phantoms was simultaneous. Decomposition of the water and fat signals was performed using a complex-based water-fat separation algorithm. Overall, a good agreement was observed between the fat fraction, T2* and phase map values of the virtual and numerical phantoms. In particular, fat fractions of 10.5±0.1 (vs 10% of the numerical phantom), 20.3±0.1 (vs 20%) and 30.4±0.1 (vs 30%) were obtained in virtual phantoms. The ViP MRI method allows for generating imaging phantoms that i) mimic water-fat systems and ii) can be analyzed with water-fat separation algorithms based on complex data. Copyright © 2016 Elsevier Inc. All rights reserved.

EXPERIMENT ON EFFECTS OF LOE-PROTEIN DIET SUPPLEMENTED WITH α-KETOACIDS ON HYPERTROPHY OF DIABETIC GLOMERULUS AND ITS RELATIONSHIP WITH THE LEVEL OF CYCLIN KINASE INHIBITOR P27

OpenAIRE

Zhou, Yi; Yuan, Weijie; Dong, Ting; Wang, Ling

2012-01-01

Low-protein diet supplemented with α-keto acids was reported to have renoprotective roles in diabetic nephropathy via inhibiting glomerular hypertrophy, however, the mechanism has not yet been fully clarified. the cyclin kinase inhibitor p27 play an important role in hypertrophy of diabetic glomerulus, The objective of the present study was to investigate the relationship between the cyclin kinase inhibitor p27 and the effect of low-protein diet supplemented with α-keto acids on hypertrophy o...

Protect Your Heart: Choose Healthy Fats

Science.gov (United States)

... peanut butter and peanut oil Polyunsaturated fat: Polyunsaturated fat, another type of unsaturated fat, protects your heart. Sources of ... paste • safflower oil • walnuts • salad dressings Omega-3 fats: This type of fat helps prevent clogging of the arteries. ...

Effects of a Modified German Volume Training Program on Muscular Hypertrophy and Strength.

Science.gov (United States)

Amirthalingam, Theban; Mavros, Yorgi; Wilson, Guy C; Clarke, Jillian L; Mitchell, Lachlan; Hackett, Daniel A

2017-11-01

Amirthalingam, T, Mavros, Y, Wilson, GC, Clarke, JL, Mitchell, L, and Hackett, DA. Effects of a modified German volume training program on muscular hypertrophy and strength. J Strength Cond Res 31(11): 3109-3119, 2017-German Volume Training (GVT), or the 10 sets method, has been used for decades by weightlifters to increase muscle mass. To date, no study has directly examined the training adaptations after GVT. The purpose of this study was to investigate the effect of a modified GVT intervention on muscular hypertrophy and strength. Nineteen healthy men were randomly assign to 6 weeks of 10 or 5 sets of 10 repetitions for specific compound resistance exercises included in a split routine performed 3 times per week. Total and regional lean body mass, muscle thickness, and muscle strength were measured before and after the training program. Across groups, there were significant increases in lean body mass measures, however, greater increases in trunk (p = 0.043; effect size [ES] = -0.21) and arm (p = 0.083; ES = -0.25) lean body mass favored the 5-SET group. No significant increases were found for leg lean body mass or measures of muscle thickness across groups. Significant increases were found across groups for muscular strength, with greater increases in the 5-SET group for bench press (p = 0.014; ES = -0.43) and lat pull-down (p = 0.003; ES = -0.54). It seems that the modified GVT program is no more effective than performing 5 sets per exercise for increasing muscle hypertrophy and strength. To maximize hypertrophic training effects, it is recommended that 4-6 sets per exercise be performed, as it seems gains will plateau beyond this set range and may even regress due to overtraining.

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Directory of Open Access Journals (Sweden)

Gabriele G. Schiattarella

2018-05-01

Full Text Available Left ventricular hypertrophy (LVH is a major contributor to the development of heart failure (HF. Alterations in cyclic adenosine monophosphate (cAMP-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA anchor proteins (AKAPs, tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-, Akap1 heterozygous (Akap1+/-, and their wild-type (wt littermates underwent transverse aortic constriction (TAC or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2 knockout mice (Siah2-/-. Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

Science.gov (United States)

Schiattarella, Gabriele G; Boccella, Nicola; Paolillo, Roberta; Cattaneo, Fabio; Trimarco, Valentina; Franzone, Anna; D'Apice, Stefania; Giugliano, Giuseppe; Rinaldi, Laura; Borzacchiello, Domenica; Gentile, Alessandra; Lombardi, Assunta; Feliciello, Antonio; Esposito, Giovanni; Perrino, Cinzia

2018-01-01

Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 ( Akap1 -/- ), Akap1 heterozygous ( Akap1 +/- ), and their wild-type ( wt ) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1 -/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 ( Siah2 ) knockout mice ( Siah2 -/- ). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

Normal range of hepatic fat fraction on dual- and triple-echo fat quantification MR in children.

Science.gov (United States)

Shin, Hyun Joo; Kim, Hyun Gi; Kim, Myung-Joon; Koh, Hong; Kim, Ha Yan; Roh, Yun Ho; Lee, Mi-Jung

2015-01-01

To evaluate hepatic fat fraction on dual- and triple-echo gradient-recalled echo MRI sequences in healthy children. We retrospectively reviewed the records of children in a medical check-up clinic from May 2012 to November 2013. We excluded children with abnormal laboratory findings or those who were overweight. Hepatic fat fraction was measured on dual- and triple-echo sequences using 3T MRI. We compared fat fractions using the Wilcoxon signed rank test and the Bland-Altman 95% limits of agreement. The correlation between fat fractions and clinical and laboratory findings was evaluated using Spearman's correlation test, and the cut-off values of fat fractions for diagnosing fatty liver were obtained from reference intervals. In 54 children (M:F = 26:28; 5-15 years; mean 9 years), the dual fat fraction (0.1-8.0%; median 1.6%) was not different from the triple fat fraction (0.4-6.5%; median 2.7%) (p = 0.010). The dual- and triple-echo fat fractions showed good agreement using a Bland-Altman plot (-0.6 ± 2.8%). Eight children (14.8%) on dual-echo sequences and six (11.1%) on triple-echo sequences had greater than 5% fat fraction. From these children, six out of eight children on dual-echo sequences and four out of six children on triple-echo sequences had a 5-6% hepatic fat fraction. When using a cut-off value of a 6% fat fraction derived from a reference interval, only 3.7% of children were diagnosed with fatty liver. There was no significant correlation between clinical and laboratory findings with dual and triple-echo fat fractions. Dual fat fraction was not different from triple fat fraction. We suggest a cut-off value of a 6% fat fraction is more appropriate for diagnosing fatty liver on both dual- and triple-echo sequences in children.

Studies in Fat Grafting: Part II. Effects of Injection Mechanics on Material Properties of Fat

Science.gov (United States)

Atashroo, David; Raphel, Jordan; Chung, Michael T.; Paik, Kevin J.; Parisi-Amon, Andreina; McArdle, Adrian; Senarath-Yapa, Kshemendra; Zielins, Elizabeth R.; Tevlin, Ruth; Duldulao, Chris; Walmsley, Graham G.; Hu, Michael S.; Momeni, Arash; Domecus, Brian; Rimsa, Joe R.; Greenberg, Lauren; Gurtner, Geoffrey C.; Longaker, Michael T.; Wan, Derrick C.

2014-01-01

Background While fat grafting can address many soft tissue deficits, results remain inconsistent. In this study, we compared physical properties of fat following injection using an automated, low shear device or the modified Coleman technique. Methods Lipoaspirate was obtained from nine patients and processed for injection using either a modified Coleman technique or with an automated, low shear device. Fat was passed through a 2 mm cannula and compared to minimally processed fat. A rheometer was used to measure the storage modulus and shear rate at which tissues began to lose their solid-like properties. Viscosity was also measured and gross properties of treatment groups were qualitatively evaluated with a glass slide test. Results Fat injected through an automated, low shear device closely matched physical properties of minimally processed fat. The storage modulus (G′) of fat for the device group was greater than the modified Coleman group and the onset of breakdown was delayed. Similarly, viscosity measurement of fat from the automated device closely matched minimally processed fat and was greater than the modified Coleman group. Conclusions The physical properties of lipoaspirate processed using an automated, low shear device with a 2 mm cannula preserved the intactness of fat more than the modified Coleman technique. Our rheological data demonstrate less damage using an automated device compared to modified Coleman technique and potentially support its use for improved fat graft integrity. PMID:25028817

Changes in myonuclear domain size do not precede muscle hypertrophy during prolonged resistance-type exercise training.

Science.gov (United States)

Snijders, T; Smeets, J S J; van Kranenburg, J; Kies, A K; van Loon, L J C; Verdijk, L B

2016-02-01

Muscle fibre hypertrophy is accompanied by an increase in myonuclear number, an increase in myonuclear domain size or both. It has been suggested that increases in myonuclear domain size precede myonuclear accretion and subsequent muscle fibre hypertrophy during prolonged exercise training. In this study, we assessed the changes in muscle fibre size, myonuclear and satellite cell content throughout 12 weeks of resistance-type exercise training in young men. Twenty-two young men (23 ± 1 year) were assigned to a progressive, 12-weeks resistance-type exercise training programme (3 sessions per week). Muscle biopsies from the vastus lateralis muscle were taken before and after 2, 4, 8 and 12 weeks of exercise training. Muscle fibre size, myonuclear content, myonuclear domain size and satellite cell content were assessed by immunohistochemistry. Type I and type II muscle fibre size increased gradually throughout the 12 weeks of training (type I: 18 ± 5%, type II: 41 ± 6%, P muscle fibres. No changes in type I and type II myonuclear domain size were observed at any time point throughout the intervention. Satellite cell content increased significantly over time in both type I and type II muscle fibres (P muscle fibre hypertrophy during prolonged resistance-type exercise training in vivo in humans. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

An elderly-onset limb girdle muscular dystrophy type 1B (LGMD1B) with pseudo-hypertrophy of paraspinal muscles.

Science.gov (United States)

Furuta, Mitsuru; Sumi-Akamaru, Hisae; Takahashi, Masanori P; Hayashi, Yukiko K; Nishino, Ichizo; Mochizuki, Hideki

2016-09-01

Mutations in LMNA, encoding A-type lamins, lead to diverse disorders, collectively called "laminopathies," which affect the striated muscle, cardiac muscle, adipose tissue, skin, peripheral nerve, and premature aging. We describe a patient with limb-girdle muscular dystrophy type 1B (LGMD1B) carrying a heterozygous p.Arg377His mutation in LMNA, in whom skeletal muscle symptom onset was at the age of 65 years. Her weakness started at the erector spinae muscles, which showed marked pseudo-hypertrophy even at the age of 72 years. Her first episode of syncope was at 44 years; however, aberrant cardiac conduction was not revealed until 60 years. The p.Arg377His mutation has been previously reported in several familial LMNA-associated myopathies, most of which showed muscle weakness before the 6th decade. This is the first report of pseudo-hypertrophy of paravertebral muscles in LMNA-associated myopathies. The pseudo-hypertrophy of paravertebral muscles and the elderly-onset of muscle weakness make this case unique and reportable. Copyright © 2016 Elsevier B.V. All rights reserved.

Combination of Complex-Based and Magnitude-Based Multiecho Water-Fat Separation for Accurate Quantification of Fat-Fraction

Science.gov (United States)

Yu, Huanzhou; Shimakawa, Ann; Hines, Catherine D. G.; McKenzie, Charles A.; Hamilton, Gavin; Sirlin, Claude B.; Brittain, Jean H.; Reeder, Scott B.

2011-01-01

Multipoint water–fat separation techniques rely on different water–fat phase shifts generated at multiple echo times to decompose water and fat. Therefore, these methods require complex source images and allow unambiguous separation of water and fat signals. However, complex-based water–fat separation methods are sensitive to phase errors in the source images, which may lead to clinically important errors. An alternative approach to quantify fat is through “magnitude-based” methods that acquire multiecho magnitude images. Magnitude-based methods are insensitive to phase errors, but cannot estimate fat-fraction greater than 50%. In this work, we introduce a water–fat separation approach that combines the strengths of both complex and magnitude reconstruction algorithms. A magnitude-based reconstruction is applied after complex-based water–fat separation to removes the effect of phase errors. The results from the two reconstructions are then combined. We demonstrate that using this hybrid method, 0–100% fat-fraction can be estimated with improved accuracy at low fat-fractions. PMID:21695724

Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-δ

International Nuclear Information System (INIS)

Yan Zhencheng; Liu Daoyan; Zhang Lili; Shen Chenyi; Ma Qunli; Cao Tingbing; Wang Lijuan; Nie Hai; Zidek, Walter; Tepel, Martin; Zhu Zhiming

2007-01-01

Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-δ (PPAR-δ)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p < 0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p < 0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-δ. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-δ. Furthermore, selective silencing of PPAR-δ by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00 ± 0.06 (n = 3) to 1.91 ± 0.06 (n = 3; p < 0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-δ significantly reduced CB1 expression to 0.39 ± 0.03 (n = 3; p < 0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-δ. Both CB1 and PPAR-δ are intimately involved in therapeutic interventions against a most important cardiovascular risk factor

A Fat strange Repeller

Institute of Scientific and Technical Information of China (English)

申影; 何阅; 姜玉梅; 何大韧

2004-01-01

This article reports an observation on a fat strange repeller, which appears after a characteristic crisis observed in a kicked rotor subjected to a piecewise continuous force field. The discontinuity border in the definition range of the two-dimensional mapping, which describes the system, oscillates as the discrete time develops. At a threshold of a control parameter a fat chaotic attractor suddenly transfers to a fat transient set. The strange repeller, which appears after the crisis, is also a fat fractal. This is the reason why super-transience happens

Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy.

Science.gov (United States)

Jeong, Da-Un; Choi, Je-Yong; Kim, Dae-Won

2017-01-01

Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fat body, fat pad and adipose tissues in invertebrates and vertebrates: the nexus

Science.gov (United States)

2014-01-01

The fat body in invertebrates was shown to participate in energy storage and homeostasis, apart from its other roles in immune mediation and protein synthesis to mention a few. Thus, sharing similar characteristics with the liver and adipose tissues in vertebrates. However, vertebrate adipose tissue or fat has been incriminated in the pathophysiology of metabolic disorders due to its role in production of pro-inflammatory cytokines. This has not been reported in the insect fat body. The link between the fat body and adipose tissue was examined in this review with the aim of determining the principal factors responsible for resistance to inflammation in the insect fat body. This could be the missing link in the prevention of metabolic disorders in vertebrates, occasioned by obesity. PMID:24758278

Muscle hypertrophy: a narrative review on training principles for increasing muscle mass

OpenAIRE

Howe, Louis; Read, Paul; Waldron, Mark

2017-01-01

Developing muscle cross-sectional area has the potential to enhance performance for many athletes. Because emerging evidence challenges traditional beliefs regarding the prescription of hypertrophy-focused training programs, this review provides an overview of the current literature relating, specifically, to programming variables. Evidence-based recommendations are provided for the design of effective resistance-training programs, with the goal of increasing an athlete's skeletal muscle mass.

PPARalpha siRNA-treated expression profiles uncover the causal sufficiency network for compound-induced liver hypertrophy.

Directory of Open Access Journals (Sweden)

Xudong Dai

2007-03-01

Full Text Available Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs against the gene for peroxisome proliferator-activated receptor alpha (Ppara, our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARalpha-induced liver hypertrophy is supported by their ability to predict non-PPARalpha-induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005. Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug

Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

Science.gov (United States)

Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

2015-10-01

Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

Associations of Infant Subcutaneous Fat Mass with Total and Abdominal Fat Mass at School-Age: The Generation R Study.

Science.gov (United States)

Santos, Susana; Gaillard, Romy; Oliveira, Andreia; Barros, Henrique; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Hofman, Albert; Jaddoe, Vincent W V

2016-09-01

Skinfold thickness enables the measurement of overall and regional subcutaneous fatness in infancy and may be associated with total and abdominal body fat in later childhood. We examined the associations of subcutaneous fat in infancy with total and abdominal fat at school-age. In a population-based prospective cohort study among 821 children, we calculated total subcutaneous fat (sum of biceps, triceps, suprailiacal, and subscapular skinfold thicknesses) and central-to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thicknesses/total subcutaneous fat) at 1.5 and 24 months. At 6 years, we measured fat mass index (total fat/height(3) ), central-to-total fat ratio (trunk fat/total fat), and android-to-gynoid fat ratio (android fat/gynoid fat) by dual-energy X-ray absorptiometry and preperitoneal fat mass area by abdominal ultrasound. Central-to-total subcutaneous fat ratio at 1.5 months was positively associated with fat mass index and central-to-total fat ratio at 6 years, whereas both total and central-to-total subcutaneous fat ratio at 24 months were positively associated with all childhood adiposity measures. A 1-standard-deviation scores higher total subcutaneous fat at 24 months was associated with an increased risk of childhood overweight (odds ratio 1.70, 95% confidence interval 1.36, 2.12). These associations were weaker than those for body mass index and stronger among girls than boys. Subcutaneous fat in infancy is positively associated with total and abdominal fat at school-age. Our results also suggest that skinfold thicknesses add little value to estimate later body fat, as compared with body mass index. © 2016 John Wiley & Sons Ltd.

The soluble guanylyl cyclase activator bay 58-2667 selectively limits cardiomyocyte hypertrophy.

Directory of Open Access Journals (Sweden)

Jennifer C Irvine

Full Text Available Although evidence now suggests cGMP is a negative regulator of cardiac hypertrophy, the direct consequences of the soluble guanylyl cyclase (sGC activator BAY 58-2667 on cardiac remodeling, independent of changes in hemodynamic load, has not been investigated. In the present study, we tested the hypothesis that the NO(•-independent sGC activator BAY 58-2667 inhibits cardiomyocyte hypertrophy in vitro. Concomitant impact of BAY 58-2667 on cardiac fibroblast proliferation, and insights into potential mechanisms of action, were also sought. Results were compared to the sGC stimulator BAY 41-2272.Neonatal rat cardiomyocytes were incubated with endothelin-1 (ET(1, 60nmol/L in the presence and absence of BAY 41-2272 and BAY 58-2667 (0.01-0.3 µmol/L. Hypertrophic responses and its triggers, as well as cGMP signaling, were determined. The impact of both sGC ligands on basal and stimulated cardiac fibroblast proliferation in vitro was also determined.We now demonstrate that BAY 58-2667 (0.01-0.3 µmol/L elicited concentration-dependent antihypertrophic actions, inhibiting ET(1-mediated increases in cardiomyocyte 2D area and de novo protein synthesis, as well as suppressing ET(1-induced cardiomyocyte superoxide generation. This was accompanied by potent increases in cardiomyocyte cGMP accumulation and activity of its downstream signal, vasodilator-stimulated phosphoprotein (VASP, without elevating cardiomyocyte cAMP. In contrast, submicromolar concentrations of BAY 58-2667 had no effect on basal or stimulated cardiac fibroblast proliferation. Indeed, only at concentrations ≥10 µmol/L was inhibition of cardiac fibrosis seen in vitro. The effects of BAY 58-2667 in both cell types were mimicked by BAY 41-2272.Our results demonstrate that BAY 58-2667 elicits protective, cardiomyocyte-selective effects in vitro. These actions are associated with sGC activation and are evident in the absence of confounding hemodynamic factors, at low (submicromolar

Exposure to low dose benzo[a]pyrene during early life stages causes symptoms similar to cardiac hypertrophy in adult zebrafish.

Science.gov (United States)

Huang, Lixing; Gao, Dongxu; Zhang, Youyu; Wang, Chonggang; Zuo, Zhenghong

2014-07-15

Growing evidence indicates that polycyclic aromatic hydrocarbons (PAHs) can lead to cardiac hypertrophy and recent research indicates that exposure to low dose crude oil during early embryonic development may lead to impacts on heart health at later life stages. The aim of this study was to evaluate whether exposure during early life stages to low dose benzo[a]pyrene (BaP), as a high-ring PAH, would lead to cardiac hypertrophy at later life stages. Zebrafish were exposed to low dose BaP until 96 hpf, then transferred to clean water and maintained for a year before histological and molecular biological analysis. Our results showed that exposure to low level BaP during early life stages increased heart weight to body weight ratios and deposited collagen in the heart of adult zebrafish. ANP, BNP and c-Myc were also induced in the heart of adult zebrafish by BaP. These results proved that low level BaP exposure during early life stages caused symptoms similar to cardiac hypertrophy in adult zebrafish. Our results displayed an elevated expression of CdC42, RhoA, p-ERK1, 2 and Rac1. Therefore, the mechanism of the cardiac hypertrophy caused by BaP exposure during early life stages may be through inducing the expression of CdC42, RhoA and Rac1, together with activating ERK1, 2. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain fat embolism

International Nuclear Information System (INIS)

Sugiura, Yoshihiro; Kawamura, Yasutaka; Suzuki, Hisato; Yanagimoto, Masahiro; Goto, Yukio

1994-01-01

Recently CT and MR imaging have demonstrated that cerebral edema is present in cases of fat embolism syndrome. To simulate this we have made a model of brain-fat embolism in rats under MR imaging. In 20 rats, we did intravenous injection of heparinized blood, 1.5 ml·kg -1 taken from femoral bone marrow cavity. Twenty four hours after the injection, we examined the MR images (1.5 tesla, spin-echo method) of brains and histologic findings of brains and lungs were obtained. In 5 of 20 rats, high signal intensity on T2-weighted images and low signal intensity on T1-weighted images were observed in the area of the unilateral cerebral cortex or hippocampus. These findings showed edema of the brains. They disappeared, however, one week later. Histologic examinations showed massive micro-fat emboli in capillaries of the deep cerebral cortex and substantia nigra, but no edematous findings of the brain were revealed in HE staining. In pulmonary arteries, we also found large fat emboli. We conclude that our model is a useful one for the study of brain fat embolism. (author)

Body Fat, Abdominal Fat, and Body Fat Distribution Is Related to Left Atrial Diameter in Young Children

DEFF Research Database (Denmark)

Dencker, Magnus; Thorsson, Ola; Karlsson, Magnus K

2012-01-01

such as lean body mass, blood pressure, gender, age, and Tanner stage revealed that TBF, AFM, and AFM/TBF were all independently related to LA diameter. Differences in the different body fat measurements explained 6-9% of the variance in LA size. These results demonstrated that both total body fat, AFM...

Associations of infant subcutaneous fat mass with total and abdominal fat mass at school-age. The Generation R Study

Science.gov (United States)

Santos, Susana; Gaillard, Romy; Oliveira, Andreia; Barros, Henrique; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Hofman, Albert; Jaddoe, Vincent WV

2017-01-01

Background Skinfold thickness enables the measurement of overall and regional subcutaneous fatness in infancy and may be associated with total and abdominal body fat in later childhood. We examined the associations of subcutaneous fat in infancy with total and abdominal fat at school-age. Methods In a population-based prospective cohort study among 821 children, we calculated total subcutaneous fat (sum of biceps, triceps, suprailiacal and subscapular skinfold thicknesses) and central-to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thicknesses/total subcutaneous fat) at 1.5 and 24 months. At 6 years, we measured fat mass index (total fat/height3), central-to-total fat ratio (trunk fat/total fat) and android-to-gynoid fat ratio (android fat/gynoid fat) by dual-energy X-ray absorptiometry and preperitoneal fat mass area by abdominal ultrasound. Results Central-to-total subcutaneous fat ratio at 1.5 months was positively associated with fat mass index and central-to-total fat ratio at 6 years, whereas both total and central-to-total subcutaneous fat ratio at 24 months were positively associated with all childhood adiposity measures (pfat at 24 months was associated with an increased risk of childhood overweight (Odds Ratio 1.70 [95% Confidence Interval 1.36, 2.12]). These associations were weaker than those for body mass index and stronger among girls than boys. Conclusions Subcutaneous fat in infancy is positively associated with total and abdominal fat at school-age. Our results also suggest that skinfold thicknesses add little value to estimate later body fat, as compared to body mass index. PMID:27225335

Congenital obstructive posterior urethral membranes and recurrent urinary tract infection: a rare case of congenital hypertrophy of the verumontanum

Directory of Open Access Journals (Sweden)

Diana Bancin

2015-03-01

Full Text Available Congenital obstructive posterior urethral membranes (COPUM is a complex disease closely related to several pathological changes in kidney development and function, as a result of urinary reflux since in utero. This congenital anomaly of urinary tract potentially causes hydroureteronephrosis that is often associated with recurrent urinary tract infections and, ultimately, one of the most common causes of end-stage renal disease in children.1,2 Congenital hypertrophy of the verumontanum as part of COPUM is very rare. Only a few reports have been written on congenital hypertrophy of the vermontanum causing congenital obstructive uropathy.3-6

Major salivary gland hypertrophy model in immature rats: morphometric and histochemical epithelial cell characteristics

Directory of Open Access Journals (Sweden)

Vera V. Ivanova

2017-01-01

Full Text Available The purpose of the study is to estimate the functional state of epithelial cells of acini and ducts of major salivary glands with hypertrophy caused by repeated incisor amputations in immature rats.Materials and methods. The experiment was carried out on immature (20 days, white male rats, divided into 3 groups: intact, control and group of rats with repeated incisor amputations. Animals were taken out in 2d, 3d, 4th, 6th, 8th, 10th and 12th weeks after the first incisor amputation. Morphofunctional state of rat major salivary glands was assessed by histological (hematoxylin and eosin, histochemistrical (Alcian blue, PAS-reaction, Brachet method and morphometrical (acini area, intralobular ducts volume methods.Results. Repeated incisor amputations led to the increase of acini area and the decrease of intralobular duct volume in submandibular glands in 2nd–4th weeks of the experiment. Cytoplasm pyroninophilia of submandibular gland acinar cells was less pronounced and intensity of PAS-reaction was more pronounced than in intact animals in 3rd week of the experiment. Morphological and functional changes of parotid and sublingual gland epithelial cells were not observed after repeated amputations of incisors in immature rats.Conclusion. Repeated incisor amputations in immature male rats lead to submandibular gland acinar cell hypertrophy in the early stages of the experiment (2d–4th weeks with accumulation of glycoproteins and protein synthesis weakening in these cells. Hypertrophy of acinar cells are accompanied by retardation in the development of granular convoluted tubule cells which are the source of synthesis and secretion of the endocrine biologically active factors of submandibular glands.

Androgen interacts with exercise through the mTOR pathway to induce skeletal muscle hypertrophy.

Science.gov (United States)

Zeng, Fanxing; Zhao, Hua; Liao, Jingwen

2017-12-01

This study was designed to investigate the effects of exogenous androgen and resistance exercise on skeletal muscle hypertrophy and the role of the mammalian target of rapamycin (mTOR) signalling during the process. A total of 24 male Sprague-Dawley rats were randomly assigned to sham operation and dihydrotestosterone (DHT) implantation groups with subgroups subjected to sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and DHT+EX). The experimental procedure lasted for 10 days. The mRNA expression of androgen receptor (AR) and insulin-like growth factor I (IGF-I), the expression of myosin heavy chain (MHC), as well as the phosphorylation statuses of AR, mTOR, p70 ribosomal S6 kinase (p70 S6K ), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) were determined in the white gastrocnemius muscle. The cross sectional area and wet mass of the muscle were also measured. The cross sectional area and MHC expression were significantly higher in SHAM+EX, DHT+SED, and DHT+EX than in SHAM+SED. There was no significant difference among groups in muscle mass. The mRNA expression of AR and IGF-I and the phosphorylation of mTOR, p70 S6K , and 4EBP1 were significantly increased in DHT+SED and SHAM+EX and were significantly enhanced in DHT+EX compared with either DHT or exercise alone. These data show that DHT causes hypertrophy in skeletal muscle and that exercise has a synergistic effect on DHT-induced hypertrophy. Exercise enhances androgen-induced rapid anabolic action, which involves activation of the mTOR pathway.

Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children.

Science.gov (United States)

Dencker, Magnus; Danielson, Anton; Karlsson, Magnus K; Wollmer, Per; Andersen, Lars B; Thorsson, Ola

2017-04-01

The aim of the study was to assess possible relationships between adipocyte fatty acid-binding protein (FABP4) and total body fat (TBF), abdominal fat, body fat distribution, aerobic fitness, blood pressure, cardiac dimensions and the increase in body fat over 2 years in a community sample of children. A cross-sectional study was used in a community sample of 170 (92 boys and 78 girls) children aged 8-11 years. TBF and abdominal fat (AFM) were measured by dual-energy X-ray absorptiometry (DXA). TBF was also expressed as percentage of total body mass (BF%), and body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure (SBP and DBP) and pulse pressure (PP) were measured. Echocardiography was performed. Left atrial (LA) size was measured, and left ventricular mass (LVM) was calculated. A follow-up DXA scan was available in 152 children (84 boys and 68 girls). Frozen serum samples were analyzed for FABP4. Partial correlations, with adjustment for sex, between FABP4 vs. ln TBF, ln BF%, ln AFM, AFM/TBF and VO2PEAK were (r=0.69, 0.68, 0.69, 0.49 and -0.39, pfat or change in fat distribution were not correlated.) Conclusions: Findings from this community-based cohort of young children show that increased body fat and abdominal fat, more abdominal body fat distribution, low fitness, more LVM and increased LA, increased SBP and PP were all associated with increased levels of FABP4. Increase in TBF and abdominal fat over 2 years were also associated with increased levels of FABP4.

Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy

DEFF Research Database (Denmark)

Hinrichsen, Rebecca; Hansen, A.H.; Haunsø, S.

2008-01-01

/6-phosphorylated retinoblastoma protein (pRb) during hypertrophy and expression of an unphosphorylatable pRb mutant impaired hypertrophic growth in cardiomyocytes. Transcription factor E2F was activated by hypertrophic elicitors but activation was impaired by pharmacological inhibition of cyclin D-cdk4...

Abdominal wall fat pad biopsy

Science.gov (United States)

Amyloidosis - abdominal wall fat pad biopsy; Abdominal wall biopsy; Biopsy - abdominal wall fat pad ... is the most common method of taking an abdominal wall fat pad biopsy . The health care provider cleans the ...

Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

Science.gov (United States)

Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

2014-01-01

Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

Directory of Open Access Journals (Sweden)

Ji Zhang

Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

Fat watch: A nationwide campaign in the Netherlands to reduce fat intake-effect evaluation

NARCIS (Netherlands)

Wechem, S.N. van; Brug, J.; Assema, P. van; Kistemaker, C.; Riedstra, M.; Löwik, M.R.H.

1998-01-01

In the Netherlands, the nationwide Fat Watch campaign aiming at a reduction in fat consumption was organized from 1991 onwards. This study describes the effects of the first three consecutive campaign years on attention to fat, diet and health, attitudes, self-efficacy expectations and intentions

Evolution from increased cardiac mechanical function towards cardiomyopathy in the obese rat due to unbalanced high fat and abundant equilibrated diets