-
Sao Paulo Medical Journal = Revista... May 2003Beckwith-Wiedemann syndrome is a complex and heterogeneous overgrowth syndrome with genetic and epigenetic alterations, involving genomic imprinting and cancer... (Review)
Review
CONTEXT
Beckwith-Wiedemann syndrome is a complex and heterogeneous overgrowth syndrome with genetic and epigenetic alterations, involving genomic imprinting and cancer predisposition. Isolated hemihyperplasia is of unknown cause, and it may represent a partial or incomplete expression of Beckwith-Wiedemann syndrome.
OBJECTIVES
A clinical and molecular review and proposal of the use of an experimental protocol to provide a practical approach for the physician.
DATA SYNTHESIS
This review demonstrates the genetic and epigenetic mechanisms involved in the Beckwith-Wiedemann syndrome and isolated hemihyperplasia, and the candidate genes. To our knowledge, this is the first Brazilian protocol for research into these disorders. The results have been used at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, to elucidate the basis of Beckwith-Wiedemann syndrome and isolated hemihyperplasia, and have been applied at the Hospital Universitário of the Faculdade de Medicina.
CONCLUSIONS
Elucidation of the etiological mechanisms and use of a laboratory protocol to detect alterations in these disorders may be useful for guiding the management of such patients and genetic counseling of the families.
Topics: Beckwith-Wiedemann Syndrome; Humans; Hypertrophy
PubMed: 12920477
DOI: 10.1590/s1516-31802003000300010 -
Life Sciences Feb 2015Aerobic exercise training (AET) attenuates or reverses pathological cardiac remodeling after insults such as chronic hypertension and myocardial infarction. The... (Review)
Review
Aerobic exercise training (AET) attenuates or reverses pathological cardiac remodeling after insults such as chronic hypertension and myocardial infarction. The phenotype of the pathologically hypertrophied heart depends on the insult; therefore, it is likely that distinct types of pathological hypertrophy require different exercise regimens. However, the mechanisms by which AET improves the structure and function of the pathologically hypertrophied heart are not well understood, and exercise research uses highly inconsistent exercise regimens in diverse patient populations. There is a clear need for systematic research to identify precise exercise prescriptions for different conditions of pathological hypertrophy. Therefore, this review synthesizes existing evidence for the distinct mechanisms by which AET benefits the heart in different pathological hypertrophy conditions, suggests strategic exercise prescriptions for these conditions, and highlights areas for future research.
Topics: Cardiomegaly; Diabetic Cardiomyopathies; Exercise; Exercise Therapy; Humans; Myocardium; Ventricular Remodeling
PubMed: 25632833
DOI: 10.1016/j.lfs.2015.01.007 -
Journal of Vascular Surgery. Venous and... Mar 2022PIK3CA (activating mutations of the p110α subunit of phosphatidylinositol 3-kinases)-related overgrowth spectrums (PROS) include a variety of clinical presentations...
BACKGROUND
PIK3CA (activating mutations of the p110α subunit of phosphatidylinositol 3-kinases)-related overgrowth spectrums (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. We performed a systematic literature review to assess the current treatment options and their efficacy and safety for PROS.
METHODS
A literature search was performed in Embase, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar to retrieve studies on the treatment of hypertrophy in PROS. Randomized controlled trials, cohort studies, and case series with ≥10 patients were included in the present review. The titles, abstracts, and full text were assessed by two reviewers independently. The risk of bias was assessed using the Newcastle-Ottawa scale.
RESULTS
We included 16 studies of the treatment of hypertrophy in PROS patients, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The risk of bias grade was low for 2, medium for 12, and high for 2 studies. Of the 16 studies, 13 reported on surgical treatment and 3 reported pharmacologic treatment using phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, and 13 studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly). However, little has been reported concerning surgery and the potential benefits for other PROS entities. The reported side effects after surgical therapy were mostly prolonged wound healing or scarring. PI3K/mTOR pathway inhibition was beneficial in patients with PROS by reducing hypertrophy and systemic symptoms. The adverse effects reported included infection, changes in blood count, liver enzymes, and metabolic measures.
CONCLUSIONS
Surgery is a locally limited treatment option for specific types of PROS. A promising treatment option for PROS is pharmacologic PIK3CA inhibition. However, the level of evidence on the treatment of overgrowth in PROS patients is limited.
Topics: Class I Phosphatidylinositol 3-Kinases; Genetic Predisposition to Disease; Humans; Hypertrophy; MTOR Inhibitors; Molecular Targeted Therapy; Mutation; Phenotype; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction; Surgical Procedures, Operative; Syndrome; Treatment Outcome
PubMed: 34358672
DOI: 10.1016/j.jvsv.2021.07.008 -
Nature Reviews. Molecular Cell Biology Jan 2013The heart hypertrophies in response to developmental signals as well as increased workload. Although adult-onset hypertrophy can ultimately lead to disease, cardiac... (Review)
Review
The heart hypertrophies in response to developmental signals as well as increased workload. Although adult-onset hypertrophy can ultimately lead to disease, cardiac hypertrophy is not necessarily maladaptive and can even be beneficial. Progress has been made in our understanding of the structural and molecular characteristics of physiological cardiac hypertrophy, as well as of the endocrine effectors and associated signalling pathways that regulate it. Physiological hypertrophy is initiated by finite signals, which include growth hormones (such as thyroid hormone, insulin, insulin-like growth factor 1 and vascular endothelial growth factor) and mechanical forces that converge on a limited number of intracellular signalling pathways (such as PI3K, AKT, AMP-activated protein kinase and mTOR) to affect gene transcription, protein translation and metabolism. Harnessing adaptive signalling mediators to reinvigorate the diseased heart could have important medical ramifications.
Topics: Animals; Cardiomegaly; Energy Metabolism; Heart; Heart Failure; Humans; Mice; Protein Biosynthesis; Signal Transduction; Thyroid Hormones; Transcription, Genetic
PubMed: 23258295
DOI: 10.1038/nrm3495 -
Respirology (Carlton, Vic.) Jul 2022The airway smooth muscle (ASM) layer thickens during development. Identifying the mechanism(s) for normal structural maturation of the ASM reveals pathways susceptible...
BACKGROUND AND OBJECTIVE
The airway smooth muscle (ASM) layer thickens during development. Identifying the mechanism(s) for normal structural maturation of the ASM reveals pathways susceptible to disease processes. This study characterized thickening of the ASM layer from foetal life to childhood and elucidated the underlying mechanism in terms of hypertrophy, hyperplasia and extracellular matrix (ECM) deposition.
METHODS
Airways from post-mortem cases were examined from seven different age groups: 22-24 weeks gestation, 25-31 weeks gestation, term (37-41 weeks gestation), <0.5 year, 0.5-1 year, 2-5 years and 6-10 years. The ASM layer area (thickness), the number and size of ASM cells and the volume fraction of ECM were assessed by planimetry and stereology.
RESULTS
From late gestation to the first year of life, normalized ASM thickness more than doubled as a result of ASM hypertrophy. Thereafter, until childhood, the ASM layer grew in proportion to airway size, which was mediated by ASM hyperplasia. Hypertrophy and hyperplasia of ASM were accompanied by a proportional change in ECM such that the broad composition of the ASM layer was constant across age groups.
CONCLUSION
These data suggest that the mechanisms of ASM growth from late gestation to childhood are temporally decoupled, with early hypertrophy and subsequent proliferation. We speculate that the developing airway is highly susceptible to ASM thickening in the first year of life and that the timing of an adverse event will determine structural phenotype.
Topics: Asthma; Child; Female; Humans; Hyperplasia; Hypertrophy; Muscle, Smooth; Myocytes, Smooth Muscle; Pregnancy; Respiratory System
PubMed: 35266251
DOI: 10.1111/resp.14240 -
Cancer Research May 2022Heart failure and cancer are the leading cause of deaths worldwide. While heart failure and cancer have been considered separate diseases, it is becoming evident that...
UNLABELLED
Heart failure and cancer are the leading cause of deaths worldwide. While heart failure and cancer have been considered separate diseases, it is becoming evident that they are highly connected and affect each other's outcomes. Recent studies using experimental mouse models have suggested that heart failure promotes tumor progression. The mouse models used involve major irreversible surgery. Here, we induced heart hypertrophy via expression of activating transcription factor 3 (ATF3) in cardiomyocytes, followed by cancer cells' implantation. Tumors developing in ATF3-transgenic mice grew larger and displayed a more highly metastatic phenotype compared with tumors in wild-type mice. To address whether ATF3 expression or the cardiac outcome are necessary for tumor progression, ATF3 expression was turned off after cardiac hypertrophy development followed by cancer cell implantation. The tumor promotion phenotype and the enhancement of metastatic properties were preserved, suggesting that the failing heart per se is sufficient to promote tumor progression. Serum derived from ATF3-transgenic mice enhanced cancer cell proliferation and increased cancer cell metastatic properties in vitro. Using a cytokine array panel, multiple factors responsible for promoting tumor cell proliferation and the metastatic phenotype were identified. Interestingly, the failing heart and the tumor separately and simultaneously contributed to higher levels of these factors in the serum as well as other tissues and organs. These data suggest the existence of intimate cross-talk between the hypertrophied heart and the tumor that is mediated by secreted factors, leading to cancer promotion and disease deterioration.
SIGNIFICANCE
This work highlights the importance of early diagnosis and treatment of heart failure prior to reaching the irreversible stage that can exacerbate cancer progression.
Topics: Activating Transcription Factor 3; Animals; Cardiomegaly; Heart Failure; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasms; Ventricular Remodeling
PubMed: 35260887
DOI: 10.1158/0008-5472.CAN-21-2463 -
Clinical Research in Cardiology :... Jul 2021Ageing, hypertension and diabetes have an intricate effect on microvascular structure. In the retina, the respective contribution of remodeling and hypertrophy in such...
BACKGROUND
Ageing, hypertension and diabetes have an intricate effect on microvascular structure. In the retina, the respective contribution of remodeling and hypertrophy in such process is still unclear. We aimed at disentangling age, blood pressure and glycaemia effects on retinal microcirculation using the non-invasive adaptive optics ophthalmoscopy (AOO).
METHODS
We included 429 subjects, distributed into 4 groups according to normal (nBP) or high blood pressure (hBP) and/or normal (nGly) or high fasting glycaemia (hGly). The nBP/nGly group was stratified in age tertiles to isolate the effect of ageing. AOO was used to measure arteriolar wall thickness (WT, µm), arteriolar (aID, µm) and venular internal diameter (vID, µm) and calculate arteriolar wall-to-lumen ratio (WLR), wall cross-sectional area (WCSA, µm). One-way ANOVA for parametric variables and Kruskal-Wallis test for non-parametric variables were used for comparison among groups. A multivariate regression analysis including age, gender, BP, hGly and antihypertensive treatment was performed to calculate independent predictors of retinal remodeling.
RESULTS
WT was increased with ageing (tertile1: 22.5 ± 3.2, tertile2: 24.2 ± 3.5, tertile 3: 25.2 ± 3.8, p = 0.001) and BP (hBP: 25.2 ± 4.1 vs nBP: 23.9 ± 3.7, p = 0.003). aID decreased with BP (hBP: 90.2 ± 13.4 vs nBP: 93.6 ± 11.6, p = 0.013) and increased with glycaemia (hGly: 97.7 ± 12.5 vs nGly: 93.6 ± 11.6, p = 0.002). A multivariate analysis showed independent association of hBP with WLR; hGly with WCSA; ageing with WLR and WCSA.
CONCLUSIONS
AOO non-invasively identifies retinal structural changes in human confirming that microvascular remodeling is exclusively related to hypertension, whereas vascular growth is related to ageing and hyperglycaemia.
Topics: Adult; Aged; Aging; Biomarkers; Blood Glucose; Blood Pressure; Blood Vessels; Female; Glycemic Index; Humans; Hypertension; Hypertrophy; Male; Microcirculation; Middle Aged; Retrospective Studies; Vascular Remodeling
PubMed: 32494923
DOI: 10.1007/s00392-020-01680-3 -
BMC Pediatrics Feb 2018Temporalis muscle hypertrophy is a rare entity of masticatory muscle hypertrophy. All types of masticatory muscle hypertrophies have been documented of which temporalis... (Review)
Review
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 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.
CASE PRESENTATION
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.
CONCLUSION
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.
Topics: Child; Female; Humans; Hypertrophy; Muscular Diseases; Temporal Muscle
PubMed: 29458353
DOI: 10.1186/s12887-018-1061-7 -
American Journal of Physiology.... Dec 2015Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following... (Randomized Controlled Trial)
Randomized Controlled Trial
Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (45 ± 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH)D (37 ± 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regeneration, and hypertrophy in the presence and absence of 10 or 100 nmol 1α,25(OH)2D3. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1α,25(OH)2D3 improved muscle cell migration dynamics and resulted in improved myotube fusion/differentiation at the biochemical, morphological, and molecular level together with increased myotube hypertrophy at 7 and 10 days postdamage. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy.
Topics: Administration, Oral; Adolescent; Adult; Dietary Supplements; Humans; Hypertrophy; Muscle, Skeletal; Physical Exertion; Placebo Effect; Regeneration; Systems Biology; Vitamin D; Young Adult
PubMed: 26506852
DOI: 10.1152/ajpendo.00375.2015 -
Drug and Alcohol Dependence Mar 2011Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance... (Review)
Review
Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolic-androgenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement; (2) significant body image disturbance; (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed.
Topics: Anabolic Agents; Animals; Body Image; Humans; Hypertrophy; Hypogonadism; Performance-Enhancing Substances; Substance-Related Disorders
PubMed: 21115306
DOI: 10.1016/j.drugalcdep.2010.09.018