Browsing by Subject "Hypertrophy"
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- PublicationOpen AccessA Novel Founder Mutation in MYBPC3: Phenotypic Comparison With the Most Prevalent MYBPC3 Mutation in Spain.(Elsevier, 2016-10-28) Sabater Molina, María; Saura, Daniel; García Molina Sáez, Esperanza; González Carrillo, Josefa; Polo, Luis; Pérez Sánchez, Inmaculada; Olmo, María Carmen; Oliva Sandoval, María José; Barriales Villa, Roberto; Carbonell, Pablo; Pascual Figal, Domingo A.; Gimeno, Juan Ramón; Ciencias SociosanitariasIntroducción y objetivos: Las mutaciones en MYBPC3 son causa de miocardiopatía hipertrófica (MCH). A pesar de que la mayorı´a de ellas producen una proteína truncada, la gravedad del fenotipo es diversa. Se describe el fenotipo clínico de una nueva mutación en MYBPC3, p.Pro108Alafs*9, presente en 13 familias del sur de España, y se compara con la mutación de MYBPC3 con mayor prevalencia en dicha región (c.2308 + 1 G > A). Métodos: Se estudió a 107 familiares de 13 casos índice que tenían diagnóstico de MCH y portaban la mutación p.Pro108Alafs*9. Se realizó un anélisis del árbol genealógico, junto con una evaluación clínica y determinación del genotipo. Resultados: Se identificó en total a 54 portadores de la mutación p.Pro108Alafs*9, de los que 39 tenían MCH. Hubo 5 casos de muerte súbita en las 13 familias. La penetrancia de la enfermedad aumentaba a medida que se incrementaba la edad, y los pacientes con MCH fueron con más frecuencia varones, y estos contrajeron la enfermedad más precozmente que las mujeres. El fenotipo fue similar en la p.Pro108Alafs*9 y la c.2308 + 1 G > A, pero se observaron diferencias en varios factores de riesgo y en la supervivencia. Hubo tendencia a mayor masa ventricular izquierda en la p.Pro108Alafs*9 que en la c.2308 + 1G > A. La resonancia magnética cardiaca reveló una extensión y un patrón de fibrosis similares en ambas. Conclusiones: La mutación p.Pro108Alafs*9 se asoció a MCH, alta penetrancia y aparición de la enfermedad a mediana edad.
- PublicationOpen AccessAltered Cx43 expression during myocardial adaptation to acute and chronic volume overloading(Murcia : F. Hernández, 2003) Formigli, L.; Ibba-Manneschi, L.; Perna, A.M.; Pacini, A.; Polidori, L.; Nediani, C.; Modesti, P.A.; Nosi, Daniele; Tani, A.; Celli, A.; Neri-Serneri, G.G.; Quercioli, F.; Zecchi-Orlandini, S.Gap-junctions are specialized regions of intercellular contacts allowing electrical impulse propagation among adjacent cardiomyocytes. Connexin43 (Cx43) is the predominant gap-junction protein in the working ventricular myocardium and its reduced expression has been extensively implicated in the genesis of conduction abnormalities and re-entry arrhythmia of chronically hypertrophied hearts. In contrast, data on the role played by this protein during cardiac remodeling and early phases of developing hypertrophy are lacking. Therefore, in the present study, we investigated this issue using an experimental model of pig left ventricle (LV) volume overloading consisting in the creation of an aorto-cava fistula. At scheduled times (6, 24, 48, 96, 168 h, and 2, 3 months after surgery) echocardiographic and haemodynamic measurements were performed and myocardial biopsies were taken for the morphological and biochemical analyses. When faced with the increased load, pig myocardium underwent an initial period (from 6 up to 48 h) of remarkable tissue remodeling consisting in the occurrence of cardiomyocyte damage and apoptosis. After that time, the tissue developed a hypertrophic response that was associated with early dynamic changes (up-regulation) in Cx43 protein expression, as demonstrated by Western blot and confocal immunofluorescence analyses. However, an initial transient increase of this protein was also found after 6 h from surgery. With the progression of LV hypertrophy (from 168 hr up to 3 months), a reduction in the myocardial Cx43 expression was, instead, observed. The increased expression of Cx43 protein during acute hypertrophic response was associated with a corresponding increase in the levels of its specific mRNA, as detected by RT-PCR. We concluded that upregulation of Cx43 gap-junction protein could represent an immediate compensatory response to support the new working conditions in the early stages of ventricular overloading.
- PublicationEmbargoGenetics of hypertrophic cardiomyopathy: A review of current state.(Wiley, 2017-03-21) Sabater Molina, María; Pérez Sánchez, Inmaculada; Hernández del Rincón, Juan Pedro; Gimeno, Juan Ramón; Ciencias SociosanitariasHypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The penetrance is incomplete and it is age and gender dependent. It is accepted as a disease of the sarcomere. Sixty percent of HCM cases carry mutations in 1 of 8 sarcomere protein genes, mainly non-sense MYBPC3 and missense MYH7 variants. Young patients with severe phenotype and other clinical features are included in proposed scores for prediction of high positive genetic result. The number of genes reported as disease-causing has increased in the last few years, in some cases without robust evidence. Currently available in silico tools are not always useful for differentiation between benign and deleterious variants. There is enough information on genotypephenotype correlations to start understanding the mechanisms of the disease. Genetic and environmental modifiers have been explored with some interesting insights from miRNA studies with potential as biomarkers and therapeutic agents. There is an additional value of genetic testing in HCM for prognosis. Knowledge about genetics and functional studies are the basis of near future therapies.
- PublicationOpen AccessMuscular hypertrophy and atrophy in normal rats provoked by the administration of normal and denervated muscle extracts(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Agüera, Eduardo; Castilla, Salvador; Luque, Evelio; Jimena, Ignacio; Leiva Cepas, Fernando; Ruz Caracuel, Ignacio; Peña, JoséThis 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.
- PublicationOpen AccessMyocardial Remoding: Mechanisms and Translational Implications(2022-05) Roncalli, Jerome; Tronchère, Helene; Lax Pérez, Antonio Manuel; Kunduzova, Oxaca; Medicina
- PublicationOpen AccessNandrolone decanoate increases satellite cell numbers in the chicken pectoralis muscle(Murcia : F. Hernández, 2010) Allouh, Mohammed Z.; Rosser, Benjamin W.C.The anabolic androgenic steroid nandrolonedecanoate has minimal androgenic effects and, thus, iswidely used to induce muscle hypertrophy in bothpatients and athletes. Although increases in satellite cellnumbers and satellite cells giving rise to new myonucleiare associated with hypertrophy in many experimentalmodels, the relationship between nandrolone andsatellite cells is poorly understood. Here we test thehypothesis that nandrolone administration is associatedwith an increase in satellite cell numbers in muscle.Nandrolone was injected at weekly intervals for fourweeks into the right pectoralis muscle of female whiteleghorn chickens aged 63 days post hatch. Age/size/sexmatched control birds received saline injections. Thecontralateral pectoralis was excised for study from eachcontrol and nandrolone treated bird. An antibody againstPax7 and immunocytochemical techniques were used toidentify satellite cells. Nandrolone significantlyincreased mean pectoralis mass by approximately 22%,and mean fiber diameter by about 24%. All satellite cellindices that were quantified increased significantly inchicken pectoralis with administration of nandrolone.Nandrolone injected birds had on average higher satellitecell frequencies (#SC nuclei/all nuclei within basallamina), number of satellite cells per millimeter of fiber,and satellite cell concentrations (closer together).Myonuclei were further apart (less concentrated) innandrolone injected muscle. However, an overallincrease in myonuclear numbers was revealed by asignificantly greater mean number of myonuclei permillimeter of fiber in nandrolone injected muscle. Ourresults suggest that satellite cells may be key cellular vectors for nandrolone induced muscle fiberhypertrophy.
- PublicationOpen AccessPanoramic ultrasound requires a trained operator and specific evaluation sites to maximize its sensitivity: a comprehensive analysis of the measurement errors(Elsevier, 2022-02-08) Hernández Belmonte, Alejandro; Martínez Cava, Alejandro; García Pallarés, Jesús; Actividad Física y DeporteThis study aimed to examine the validity and repeatability of panoramic ultrasound to evaluate the anatomical cross-sectional area (ACSA) of quadriceps femoris muscles. Specifically, we aimed to quantify the errors generated during the image acquisition and analysis (repeatability), as well as when comparing with magnetic resonance imaging (MRI) (validity). Moreover, we analyzed the influence of the operator's experience and the region of the thigh, on these errors. Both thighs of 16 subjects were included. The validity and repeatability study quantified the errors made by two operators (trained and novice) when measuring ACSA of vastus lateralis (VL), vastus medialis-intermedius (VMVI), and rectus femoris (RF), in six thigh regions (from 20 to 70%). Two ACSA images were acquired 5 min apart to examine acquisition errors, whereas acquisition #1 was analyzed twice to quantify analysis errors. Thereafter, ACSA of acquisition #1 was compared with that measured by MRI. Statistics included the standard error of measurement (SEM) expressed in absolute (cm2) and relative terms (%) as a coefficient of variation (CV). Measurement errors were lower for the trained operator than for the novice: Acquisition (SEM = 0.05 – 0.78 vs. 0.25 – 1.42 cm2), analysis (SEM = 0.13 – 1.93 vs. 0.30 – 3.05 cm2) and compared-with-MRI (SEM = 0.13 – 1.93 vs. 0.30 – 3.05 cm2). Regions with the lowest errors were those located at the middle of the thigh (40–50%), although slight between-muscle differences were found: VMVI (30–40%), VL (40–50%), RF (50–60%). These findings suggest that the accurate implementation of panoramic ultrasound to measure ACSA of quadriceps femoris muscles requires a trained operator and specific evaluation sites.
- PublicationEmbargoPectoralis cross-sectional area can be accurately measured using panoramic ultrasound: a validity and repeatability study(2021-11-30) Hernández Belmonte, Alejandro; Martínez Cava, Alejandro; García Pallarés, Jesús; Actividad Física y DeporteThe objective of the current study was to examine the validity and repeatability of panoramic ultrasound in evaluating the anatomical cross-sectional area (ACSA) of the pectoralis major. Specifically, we aimed to quantify the measurement errors generated during the image acquisition and analysis (repeatability), as well as when comparing with magnetic resonance imaging (MRI) (validity). Moreover, we aimed to analyze the influence of the operator’s experience on these measurement errors. Both sides of the chest of 16 participants (n = 32) were included. Errors made by two operators (trained and novice) when measuring pectoralis major ACSA (50% of sternum areola mammae distance) were examined. Acquisition errors included the comparison of two images acquired 5 min apart. Acquisition 1 was analyzed twice to quantify analysis errors. Thereafter, acquisition 1 was compared with MRI. Statistics include the standard error of measurement (SEM), expressed in absolute (cm2) and relative (%) terms as a coefficient of variation (CV), and the calculation of systematic bias. Errors made by the trained operator were lower than those made by the novice, especially during the image acquisition (SEM = 0.25 vs. 0.66 cm2, CV = 1.06 vs. 2.98%) and when compared with MRI (SEM = 0.27 vs. 1.90 cm2, CV = 1.13 vs. 8.16%). Furthermore, although both operators underestimated the ACSA, magnitude and variability [SD] of these errors were lower for the trained operator (bias = 0.19 [0.34] cm2) than for the novice (bias = 1.97 [2.59] cm2). Panoramic ultrasound is a valid and repeatable technique for measuring pectoralis major ACSA, especially when implemented by a trained operator.
- PublicationOpen AccessSustanon induces dose-independent hypertrophy and satellite cell proliferation in slow oxidative fibers of avian skeletal muscle(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Allouh, Mohammed Z.; Jarrar, Ahmad A.; Asfour, Hasan A.; Said, Raed S.; Shaqoura, Emad I.Sustanon is a well-known anabolic drug that is used to treat hypogonadism and restore muscle mass and bone density. As research to date has been limited to its effects in glycolytic fibers, this study aimed to investigate the dose-related effects of Sustanon on the oxidative fibers of avian skeletal muscle. Adult female chickens were randomly divided into 4 groups: control (C), received a dose of 100 μl normal saline per injection; and Sustanon-1, -2, and -3 (S1, S2, and S3), that received a dose of 12.5, 25, or 50 mg/kg Sustanon per injection, respectively. Each bird received 4 injections at weekly intervals (1 injection/week). Robust histochemical and immunofluorescent techniques along with morphometric analyses were applied to determine the oxidative activity and morphological variations of the oxidative muscle fibers in all groups. Sustanontreated groups exhibited significant increases in fiber size and numbers of satellite cells and myonuclei compared to the control group. However, no significant variations were found between Sustanon-treated groups in the aforementioned indices. In conclusion, Sustanon induced oxidative fiber hypertrophy that was associated with satellite cell proliferation and myonuclear accretion in avian skeletal muscle. Furthermore, the effects of Sustanon appeared to be dose-independent.
- PublicationEmbargoThe 2-point method: A quick, accurate, and repeatable approach to estimate ultrasoundderived quadriceps femoris cross-sectional area(Human Kinetics, 2022-07-18) Hernández Belmonte, Alejandro; Martínez Cava, Alejandro; García Pallarés, Jesús; Actividad Física y DeportePurpose: To analyze the feasibility of the 2-point method for estimating ultrasound-derived quadriceps femoris cross-sectional area (QUADACSA). First, (1) the agreement between QUADACSA measured by panoramic ultrasound and magnetic resonance imaging (MRI) was studied, and thereafter, we examined 2 approaches of the 2-point method in terms of (2) estimation errors and (3) test–retest repeatability. Methods: Both thighs of 16 young men were analyzed. Ultrasound-QUADACSA versus MRI-QUADACSA comparison was conducted at 6 thigh lengths (20%–70% of the thigh length). Thereafter, ultrasound-QUADACSA corresponding to 30% and 60% (2-point30%–60%) or 20% and 70% (2-point20%–70%) were used to estimate QUADACSA of the remaining regions. Estimated QUADACSA resulting from both 2-point approaches was compared with the measured one. Finally, the test–retest repeatability was examined by comparing the errors generated on 2 separate estimations. Statistics included the standard error of measurement (SEM) expressed in absolute (in square centimeters) and relative terms (in percentage) as a coefficient of variation (CV), as well as the intraclass correlation cofficient (ICC) and bias. Results: An excellent agreement (ICC ≥ 0.980) and reduced errors (SEM ≤ 2.43 cm2) resulted from the ultrasound-QUADACSA versus MRI-QUADACSA comparison. Although estimation errors found were reduced (CV ≤ 7.50%), they proved to be lower and less biased for the 2-point30%–60%, especially at the central regions (SEM ≤ 2.01 cm2; bias ≤ 0.89 cm2). Similarly, repeatability analysis revealed lower test–retest errors for the 2-point30%–60% (CV ≤ 1.9%) than for the 2-point20%–70% (CV ≤ 4.6%). Conclusion: The 2-point method, especially that implemented using the 30% and 60% regions, represents an accurate and repeatable strategy to evaluate QUADACSA.
- PublicationOpen AccessThe hypertrophic chondrocyte: To be or not to be(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Hallett, Shawn A.; Ono, Wanida; Ono, NoriakiHypertrophic chondrocytes are the master regulators of endochondral ossification; however, their ultimate cell fates cells remain largely elusive due to their transient nature. Historically, hypertrophic chondrocytes have been considered as the terminal state of growth plate chondrocytes, which are destined to meet their inevitable demise at the primary spongiosa. Chondrocyte hypertrophy is accompanied by increased organelle synthesis and rapid intracellular water uptake, which serve as the major drivers of longitudinal bone growth. This process is delicately regulated by major signaling pathways and their target genes, including growth hormone (GH), insulin growth factor-1 (IGF-1), indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), bone morphogenetic proteins (BMPs), sex determining region Y-box 9 (Sox9), runt-related transcription factors (Runx) and fibroblast growth factor receptors (FGFRs). Hypertrophic chondrocytes orchestrate endochondral ossification by regulating osteogenic-angiogenic and osteogenic-osteoclastic coupling through the production of vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and matrix metallopeptidases-9/13 (MMP-9/13). Hypertrophic chondrocytes also indirectly regulate resorption of the cartilaginous extracellular matrix, by controlling formation of a special subtype of osteoclasts termed "chondroclasts". Notably, hypertrophic chondrocytes may possess innate potential for plasticity, reentering the cell cycle and differentiating into osteoblasts and other types of mesenchymal cells in the marrow space. We may be able to harness this unique plasticity for therapeutic purposes, for a variety of skeletal abnormalities and injuries. In this review, we discuss the morphological and molecular properties of hypertrophic chondrocytes, which carry out important functions during skeletal growth and regeneration.
- PublicationOpen AccessThe pathology of the atrophylhypertrophy complex (AHC) of the liver. A light microscopic and immunohistochemical study(Murcia : F. Hernández, 1994) Lory, J.; Schweizer, W.; Blumgart, L.H.; Zimmermann, AstridThe term, atrophylhypertrophy complex (AHC) of the liver, denotes a distinct combination of hepatic atrophy and hypertrophy occurring in situations of significant impairment of bile flow andlor portal or hepatic venous blood flow. In the lobes or segments concerned atrophy ensues, whereas areas not or less involved develop compensatory hypertrophy, resulting in a characteristic gross deformity of the organ and, in some instances, in rotation of the liver around a virtual hilar axis. As recognition and early detection of AHC have a strong implication on the treatment of several hepatobiliary diseases, adequate combined clinical, radiological and histopathological strategies have to be used in order to arrive at a correct diagnosis. The present investigation was designed to analyze the morphology of AHC in detail and to define lesion patterns having the highest predictive value. For atrophy, the following features were highly characteristic: 1) Advanced septal fibrosis with or without nodular change of parenchyma; 2) Biliary piecemeal necrosis with formation of vascular structures; 3) Ductular proliferations, frequently extending into septa and involving the parenchyma; 4) Capillarization of sinusoids with type IV collagen deposition in Disse's space; 5) Factor VIII-associated antigen expression by sinusoidal endothelia; 6) a seemingly paradoxical increase of proliferative activity of hepatocytes as based on PCNA staining. The severity of lesions in atrophy was related to the type of underlying disease, in that the changes were clearly more expressed in situations of longstanding obstruction due to benign disease. Using a set of well-defined morphological parameters, atrophy can be reproducibly distinguished from hypertrophy in biopsy material from AHC.
- PublicationOpen AccessWhey protein: How does it affect the increase in muscle mass of untrained athletes post weight training?(Servicio de Publicaciones. Universidad de Murcia, 2025) Pratama, Angga Okta; Yenes, Ronni; Irawan, Roma; Ramadhan, Riang Hari; Maidarman; Yendrizal; Sin departamento asociadoWeight training is a type of exercise that can provide many benefits for the body. Apart from exercise programs, the nutritional intake consumed also influences the success of building muscle through weight training. Protein is the main element that influences muscle growth and development after doing weight training. This experimental study used a pretest-posttest control group design to examine the effect of whey protein on muscle hypertrophy. It involved 60 male student athletes from Padang, Indonesia, aged 18-25 with a BMI of 25-29, physically healthy, and willing to follow research guidelines. The experimental group (n = 30) was given whey protein 30 minutes after weight training as much as ± 45 grams while the control group (n = 30) was only given mineral water after weight training. Muscle hypertrophy was measured using a measuring tape and skinfold calipers. Muscle circumference was calculated using the formula: MTC − (3.14 × TSF), where MTC is the muscle circumference and TSF is the triceps skinfold thickness. The results indicated that the group consuming whey protein experienced a significantly greater increase in muscle circumference compared to the control group (p<0.05). Based on research findings, planned and structured weight training combined with whey protein supplementation can maximize muscle hypertrophy compared to training without whey protein.