ABSTRACT
OBJECTIVE: Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. METHODS: EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. RESULTS: Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82-20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. CONCLUSIONS: This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables.
Subject(s)
Osteoarthritis, Knee , Osteoarthritis , Cross-Sectional Studies , Female , Humans , Life Style , Osteoarthritis/epidemiology , Phenotype , Prevalence , Spain/epidemiologyABSTRACT
INTRODUCTION: The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). OBJECTIVE: To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. MATERIAL AND METHODS: Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. RESULTS: The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. CONCLUSION: The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent.
Subject(s)
Osteoarthritis, Hip , Osteoarthritis, Knee , Aged , Cross-Sectional Studies , Female , Humans , Middle Aged , Osteoarthritis, Hip/epidemiology , Prevalence , Spain/epidemiologyABSTRACT
Introducción: La Sociedad Española de Reumatología elaboró en el año 2000 el estudio EPISER2000 para conocer la prevalencia de la artrosis y otras enfermedades reumáticas en España. Los cambios sociodemográficos y en los hábitos de vida ocurridos en los últimos años en España justifican actualizar los datos de las enfermedades reumáticas (EPISER2016). Objetivo: Estimar la prevalencia de artrosis sintomática de columna cervical, columna lumbar, cadera, rodilla y mano, en población adulta en España. Material y métodos: Estudio transversal de base poblacional. Se realizó un muestreo aleatorizado polietápico estratificado y por conglomerados. Los participantes fueron contactados por teléfono para cumplimentar un cuestionario de cribado de artrosis. El reumatólogo confirmaba o descartaba el diagnóstico. Se utilizaron los criterios-clínicos-ACR para diagnosticar artrosis de manos y los criterios clínico-radiológicos-ACR para diagnosticar la artrosis de rodilla y cadera. Resultados: La prevalencia de artrosis en España en una o más de las localizaciones estudiadas fue de 29,35%. La prevalencia de artrosis-cervical fue del 10,10% y de artrosis-lumbar del 15,52%. Ambas son más frecuentes en mujeres y a mayor edad, así como en personas con niveles de estudios bajos y obesidad. La prevalencia de artrosis de cadera fue del 5,13% y la de artrosis de rodilla del 13,83%; estas se asocian con el sexo femenino, sobrepeso y obesidad, menor frecuencia en nivel de estudios alto y con la edad. La prevalencia de la artrosis de mano fue del 7,73%. Es más frecuente en mujeres, obesas, con bajo nivel de estudios y mayor edad. Conclusiones: El estudio EPISER2016 es el primero que analiza la prevalencia de artrosis sintomática en 5 localizaciones (columna cervical, lumbar, rodilla, cadera y manos) en España. La artrosis de la columna lumbar es la más prevalente.(AU)
Introduction: The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). Objective: To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. Material and methods: Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. Results: The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. Conclusion: The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent.(AU)
Subject(s)
Humans , Male , Female , Prevalence , Joint Diseases , 29161 , Habits , Prevalence Ratio , Osteoarthritis, Hip , Osteoarthritis, Knee , Osteoarthritis, Spine , Osteoarthritis , Rheumatology , Cross-Sectional StudiesABSTRACT
INTRODUCTION: The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). OBJECTIVE: To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. MATERIAL AND METHODS: Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. RESULTS: The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. CONCLUSION: The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent.
ABSTRACT
Ghrelin (GRL) is a gut-brain hormone with a role in a wide variety of physiological functions in mammals and fish, which points out the ghrelinergic system as a key element for the appropriate biological functioning of the organism. However, many aspects of the multifunctional nature of GRL remain to be better explored, especially in fish. In this study, we used the CRISPR/Cas9 genome editing technique to generate F0 zebrafish in which the expression of grl is compromised. Then, we employed high-throughput mRNA sequencing (RNA-seq) to explore changes in the brain transcriptome landscape associated with the silencing of grl. The CRISPR/Cas9 technique successfully edited the genome of F0 zebrafish resulting in individuals with considerably lower levels of GRL mRNAs and protein and ghrelin O-acyl transferase (goat) mRNAs in the brain, intestine, and liver compared to wild-type (WT) zebrafish. Analysis of brain transcriptome revealed a total of 1360 differentially expressed genes (DEGs) between the grl knockdown (KD) and WT zebrafish, with 664 up- and 696 downregulated DEGs in the KD group. Functional enrichment analysis revealed that DEGs are highly enriched for terms related to morphogenesis, metabolism (especially of lipids), entrainment of circadian clocks, oxygen transport, apoptosis, and response to stimulus. The present study offers valuable information on the central genes and pathways implicated in functions of GRL, and points out the possible involvement of this peptide in some novel functions in fish, such as apoptosis and oxygen transport.
Subject(s)
Brain/physiology , Ghrelin/genetics , Zebrafish/genetics , Animals , Clustered Regularly Interspaced Short Palindromic Repeats , TranscriptomeABSTRACT
Physiological mechanisms driving stress response in vertebrates are evolutionarily conserved. These mechanisms involve the activation of both the hypothalamic-sympathetic-chromaffin cell (HSC) and the hypothalamic-pituitary-adrenal (HPA) axes. In fish, the reduction of food intake levels is a common feature of the behavioral response to stress but the central mechanisms coordinating the energetic response are not well understood yet. In this work, we explore the effects of acute stress on key central systems regulating food intake in fish as well as on total body cortisol and glucose levels. We show that acute stress induced a rapid increase in total body cortisol with no changes in body glucose, at the same time promoting a prompt central response by activating neuronal pathways. All three orexigenic peptides examined, i.e., neuropeptide y (npy), agouti-related protein (agrp), and ghrelin, increased their central expression level suggesting that these neuronal systems are not involved in the short-term feeding inhibitory effects of acute stress. By contrast, the anorexigenic precursors tested, i.e., cart peptides and pomc, exhibited increased expression after acute stress, suggesting their involvement in the anorexigenic effects.
Subject(s)
Eating , Feeding Behavior/physiology , Gene Expression Regulation/physiology , Stress, Physiological , Zebrafish/physiology , Animals , Glucose/metabolism , Hydrocortisone/metabolism , Time Factors , TranscriptomeABSTRACT
Melanocortin signaling is regulated by the binding of naturally occurring antagonists, agouti-signaling protein (ASIP) and agouti-related protein (AGRP) that compete with melanocortin peptides by binding to melanocortin receptors to regulate energy balance and growth. Using a transgenic model overexpressing ASIP, we studied the involvement of melanocortin system in the feeding behaviour, growth and stress response of zebrafish. Our data demonstrate that ASIP overexpression results in enhanced growth but not obesity. The differential growth is explained by increased food intake and feeding efficiency mediated by a differential sensitivity of the satiety system that seems to involve the cocaine- and amphetamine- related transcript (CART). Stress response was similar in both genotypes. Brain transcriptome of transgenic (ASIP) vs wild type (WT) fish was compared using microarrays. WT females and males exhibited 255 genes differentially expressed (DEG) but this difference was reduced to 31 after ASIP overexpression. Statistical analysis revealed 1122 DEG when considering only fish genotype but 1066 and 981 DEG when comparing ASIP males or females with their WT counterparts, respectively. Interaction between genotype and sex significantly affected the expression of 97 genes. Several neuronal systems involved in the control of food intake were identified which displayed a differential expression according to the genotype of the fish that unravelling the flow of melanocortinergic information through the central pathways that controls the energy balance. The information provided herein will help to elucidate new central systems involved in control of obesity and should be of invaluable use for sustaining fish production systems.
Subject(s)
Agouti Signaling Protein/genetics , Brain/metabolism , Zebrafish/genetics , Agouti Signaling Protein/metabolism , Agouti-Related Protein/genetics , Agouti-Related Protein/metabolism , Animals , Animals, Genetically Modified , Eating/physiology , Energy Metabolism/genetics , Feeding Behavior/physiology , Female , Gene Expression Profiling , Gene Expression Regulation , Male , Melanocortins/antagonists & inhibitors , Neural Pathways/metabolism , Zebrafish/metabolismABSTRACT
For dentists, there is little information on malignant tumors and complications both because their natural evolution is secondary to treatment, despite cancer in children represents 3 percent of all cancer cases. The goal is to make a brief review of the most common neoplasm in children, to identify them and find out the oral alterations with highest incidence both as secondary to the pathology and as a side effect of treatment. This review analyses various types of malignant neoplasms which may occur in this stage of life. They are divided into haematological: leukemias, lymphomas and solid tumors. The most common leukemia is acute lymphoblastic (ALL) followed by acute myeloid and granulocytic. Lymphomas develop from the lymphatic system and are divided into Hodgkins and non-Hodgkins. Cancer has become a chronic disease favoring a new group of patients who achieve survival but suffer side effects due to therapies, drugs, doses and the childs characteristics. Oral complications appear in 40 percent of cases and the most frequent are mucositis, opportunistic infection, xerostomia, bleeding, periodontal disease and disorders in the development of teeth and jaw. Although cancer is located outside of the maxillofacial area, chemotherapy is aggressive for a developing organism. The side effects of radiation therapy affect the general and specific area to radiate as well as the surrounding organs and tissues. Recently, advances in diagnosis and treatment have increased survival from 20 percent to 80 percent, with long-term treatment.
Existe poca información para el odontólogo sobre tumores malignos y complicaciones por su evolución natural como secundaria al tratamiento a pesar de ser el cáncer en niños el 3 por ciento de todos los cánceres. El objetivo es hacer una revisión sucinta de las neoplasias más frecuentes en niños, identificarlas y conocer las alteraciones orales con mayor incidencia secundarias tanto a la patología como el efecto secundario del tratamiento. Realizamos una revisión analizando los diferentes tipos de neoplasias malignas que puede presentarse en esta etapa de vida, las cuales se dividen en hematológicos: leucemias y linfomas y tumores sólidos. La leucemia más frecuente es la linfoblastica aguda (LLA), después la Mieloide Aguda, y Granulocítica. Los linfomas se desarrollan del sistema linfático, se dividen en Hodgkin y no Hodgkin. El cáncer se ha convertido en una enfermedad crónica. Ello favorece un nuevo grupo de pacientes que logran supervivencia suficiente para que puedan producirse efectos secundarios por las terapias utilizadas, fármacos, dosis y las características de cada niño. Las complicaciones orales aparecen en un 40 por ciento, las más frecuentes: mucositis, infección oportunista, xerostomía, hemorragias, enfermedad periodontal, alteraciones del desarrollo de dientes y maxilar. Aunque el cáncer esté localizado fuera del área maxilofacial, la quimioterapia es agresiva en un organismo en desarrollo. Los efectos secundarios de la radioterapia son generales y específicos de la zona a irradiar, órganos y tejidos circundantes. Últimamente, los avances en diagnóstico y tratamiento aumentaron la supervivencia del 20 por ciento al 80 por ciento, con tratamientos a largo plazo.
Subject(s)
Humans , Child , Drug-Related Side Effects and Adverse Reactions , Neoplasms/complications , Tooth Diseases/etiology , Radiotherapy/adverse effectsABSTRACT
The melanocortin system is one of the most complex of the hormonal systems. It involves different agonists encoded in the multiplex precursor proopiomelanocortin (POMC) or in different genes as ß-defensins, endogenous antagonist, like agouti-signalling protein (ASIP) or agouti-related protein (AGRP), and five different melanocortin receptors (MCRs). Rounds of whole genome duplication events have preceded the functional and molecular diversification of the family in addition some co-evolutionary and tandem duplication processes have been proposed. The evolutionary patterns of the different partners are controversial and different hypotheses have emerged from a study of the sequenced genomes. In this review, we summarize the different evolutionary hypotheses proposed for the different melanocortin partners.
Subject(s)
Agouti Signaling Protein/genetics , Agouti-Related Protein/genetics , Evolution, Molecular , Melanocortins , Pro-Opiomelanocortin/genetics , Receptors, Melanocortin/genetics , Agouti Signaling Protein/physiology , Agouti-Related Protein/physiology , Amino Acid Sequence , Animals , Humans , Melanocortins/genetics , Melanocortins/metabolism , Molecular Sequence Data , Receptors, Melanocortin/antagonists & inhibitors , Sequence HomologyABSTRACT
The melanocortin system is probably one of the most complex hormonal systems since it integrates agonist, encoded in the proopiomelanocortin precursor, endogenous antagonist, agouti signaling protein and agouti-related protein, five different G-protein coupled receptors and two accessory proteins. These accessory proteins interact with melanocortin receptors to allow traffic to the plasma membrane or to regulate the pharmacological profile. The MC1R fill the extension locus, which is primarily responsible for the regulation of pigmentation. In zebrafish, both MC1R and MRAP2 system are expressed in the skin. We demonstrate that zebrafish MC1R physically, or closely, interacts with the MRAP2 system, although this interaction did not result in modification of the studied pharmacological profile. However, progressive fasting induced skin darkening but also an upregulation of the MRAP2 expression in the skin, suggesting an unknown role for MRAP2a that could involve receptor desensitization processes. We also demonstrate that crowding stress induces skin darkening and a downregulation of MC1R expression in the skin.
Subject(s)
Carrier Proteins/metabolism , Hormones/pharmacology , Receptor, Melanocortin, Type 1/metabolism , Skin Pigmentation/physiology , Zebrafish Proteins/metabolism , Zebrafish/metabolism , Adrenocorticotropic Hormone/pharmacology , Agouti Signaling Protein/genetics , Agouti Signaling Protein/metabolism , Agouti-Related Protein/genetics , Agouti-Related Protein/metabolism , Animals , Blotting, Western , Carrier Proteins/genetics , Cyclic AMP/metabolism , Fasting , Fluorescent Antibody Technique , Immunoenzyme Techniques , Immunoprecipitation , Intracellular Signaling Peptides and Proteins , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptor, Melanocortin, Type 1/genetics , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Skin Pigmentation/drug effects , Stress, Physiological , Zebrafish/growth & development , Zebrafish Proteins/genetics , alpha-MSH/pharmacologyABSTRACT
The melanocortin system is one of the most complex hormonal systems in vertebrates. Atypically, the signaling of melanocortin receptors is regulated by the binding of endogenous antagonists, named agouti-signaling protein (ASIP) and agouti-related protein (AGRP). Teleost specific genome duplication (TSGD) rendered new gene copies in teleost fish and up to four different genes of the agouti family of peptides have been characterized. In this paper, molecular cloning was used to characterize mRNA of the agouti family of peptides in sea bass. Four different genes were identified: AGRP1, ASIP1, AGRP2 and ASIP2. The AGRP1 gene is mainly expressed in the brain whereas ASIP1 is mainly expressed in the ventral skin. Both ASIP2 and AGRP2 are expressed in the brain and the pineal gland but also in some peripheral tissues. Immunocytochemical studies demonstrated that AGRP1 is exclusively expressed within the lateral tuberal nucleus, the homologue of the mammalian arcuate nucleus in fish. Long-term fasting (8-29 days) increased the hypothalamic expression of AGRP1 but depressed AGRP2 expression (15-29 days). In contrast, the hypothalamic expression of ASIP2 was upregulated during short-term fasting suggesting that this peptide could be involved in the short term regulation of food intake in the sea bass.
Subject(s)
Agouti-Related Protein/genetics , Bass/genetics , Gene Expression Profiling , Gene Expression Regulation , Peptides/genetics , Agouti-Related Protein/chemistry , Agouti-Related Protein/metabolism , Amino Acid Sequence , Animals , Base Sequence , Bass/metabolism , Brain/cytology , Brain/metabolism , Fasting/physiology , Molecular Sequence Data , Peptides/chemistry , Peptides/metabolism , Phylogeny , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Sequence Alignment , Tissue DistributionABSTRACT
BACKGROUND: Collagen-glycosaminoglycan scaffolds, originally designed to treat severe burns, are now commonly used in patients with complex wounds associated with diabetes mellitus. In this study, the authors investigated how the thickness of the scaffold would affect cellular integration with the diabetic host and whether this can be accelerated using subatmospheric pressure wound therapy devices. METHODS: Collagen-glycosaminoglycan scaffolds, 500 to 2000-µm thick, were applied to dorsal wounds in genetically diabetic mice. In addition, 1000-µm collagen-glycosaminoglycan scaffolds with and without silicone were treated with a subatmospheric pressure device (-125 mmHg). On days 5 and 10, cellular and vascular integration of tissues was studied by histology, immunohistochemistry, corrosion casting, and qRT-polymerase chain reaction. RESULTS: Cells and vessels from the wound surface populated the scaffold to form layers with varying cellular density. Areas of high cell density and proliferation were noted at the bottom of the scaffold. Increasing the thickness of the scaffold did not affect the extent of cellular ingrowth, so that thicker scaffolds had a thicker residual acellular layer on the surface. The thickness of cellular ingrowth was stable between days 5 and 10, whereas vessels seen in the scaffolds on day 10 were not yet present on day 5. Subatmospheric pressure devices applied to silicone-covered collagen-glycosaminoglycan scaffolds minimized the granulation tissue formation beneath the scaffold, which enhanced vessel ingrowth. CONCLUSIONS: The early kinetics of cellular integration into collagen-glycosaminoglycan scaffolds is independent of scaffold thickness in a diabetic wound model. Scaffold adherence to the wound and integration can be improved using a subatmospheric pressure device.
Subject(s)
Collagen/physiology , Diabetes Complications , Glycosaminoglycans/physiology , Skin , Tissue Scaffolds , Wounds and Injuries/surgery , Animals , Kinetics , Male , Mice , Mice, Inbred Strains , Regeneration/physiology , Wounds and Injuries/physiopathologyABSTRACT
Melanocortin 2 receptor (MC2R) is the only canonical ACTH receptor. Its functional expression requires the presence of an accessory protein, known as melanocortin receptor 2 accessory protein 1 (MRAP1). The vertebrate genome exhibits a paralogue gene called MRAP2, which is duplicated in zebrafish (MRAP2a and MRAP2b), although its function remains unknown. In this paper, we demonstrate that MRAP2a enables MC4R, a canonical MSH receptor, to be activated by ACTH with a similar sensitivity to that exhibited by MC2R. Both proteins physically interact and are coexpressed in the neurons of the preoptic area, a key region in the control of the energy balance and hypophyseal secretion in fish. ACTH injections inhibit food intake in wild-type zebrafish but not in fish lacking functional MC4R. Both MRAP1 and MRAP2a are hormonally regulated, suggesting that these proteins are substrates for feed-back regulatory pathways of melanocortin signaling. Fasting has no effect on the central expression of MRAP2a but stimulates MRAP2b expression. This protein interacts and is colocalized with MC4R in the tuberal hypothalamic neurons but has no effect on the pharmacologic profile of MC4R. However, MRPA2b is able to decrease basal reporter activity in cell lines expressing MC4R. It is plausible that MRAP2b decreases the constitutive activity of the MC4R during fasting periods, driving the animal toward a positive energy balance. Our data indicate that MRAP2s control the activity of MC4R, opening up new pathways for the regulation of melanocortin signaling and, by extension, for the regulation of the energy balance and obesity.
Subject(s)
Carrier Proteins/metabolism , Gene Expression , Receptor, Melanocortin, Type 4/metabolism , Receptors, Corticotropin/metabolism , Zebrafish Proteins/metabolism , Adrenocorticotropic Hormone/physiology , Animals , Bezafibrate/pharmacology , Carrier Proteins/genetics , Energy Intake , Female , HEK293 Cells , Humans , Hydrocortisone/physiology , Intracellular Signaling Peptides and Proteins , Male , Peroxisome Proliferator-Activated Receptors/agonists , Peroxisome Proliferator-Activated Receptors/metabolism , Protein Interaction Mapping , Protein Transport , Receptor, Melanocortin, Type 4/genetics , Receptors, Corticotropin/genetics , Triiodothyronine/physiology , Zebrafish , Zebrafish Proteins/geneticsABSTRACT
The activation of melanocortin 2 receptor (MC2R) by ACTH mediates the signaling cascade leading to steroid synthesis in the interrenal tissue (analogous to the adrenal cortex in mammals) of fish. However, little is known about the functional regulation of this receptor in fish. In this work described, we cloned sea bass MC2R from a liver cDNA. SbMC2R requires the melanocortin 2 receptor accessory protein (MRAP) for its functional expression. Dietary cortisol but not long-term stress protocols downregulated interrenal sbMC2R expression. Data suggest the existence of a negative feedback on interrenal sbMC2R expression imposed by local or systemic glucocorticoids. This feedback could be involved in long-term stress adaptation by regulating interrenal sensitivity to ACTH. ACTH-induced MC2R activation stimulates hepatic lipolysis, suggesting that ACTH may mediate stress-induced effects upstream of cortisol release.
Subject(s)
Adaptation, Biological/genetics , Bass/genetics , Bass/metabolism , Receptor, Melanocortin, Type 2/genetics , Receptor, Melanocortin, Type 2/metabolism , Stress, Physiological/genetics , Adrenocorticotropic Hormone/pharmacology , Amino Acid Sequence , Animals , CHO Cells , Cloning, Molecular , Cricetulus , Fasting , Gene Expression , Gene Expression Regulation/drug effects , Lipid Metabolism/drug effects , Liver/drug effects , Liver/metabolism , Molecular Sequence Data , Organ Specificity/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Melanocortin, Type 2/agonists , Receptor, Melanocortin, Type 2/chemistry , Sequence AlignmentABSTRACT
OBJECTIVE: To evaluate the ability of a tumor-head volume ratio to predict outcome and incidence of hydrops in fetuses with sacrococcygeal teratoma. METHODS: Seventy-one sonograms were reviewed retrospectively from 28 fetuses with sacrococcygeal teratoma managed in our institution. Head volume (HV) and total tumor volume were calculated from sonograms. Amount of cystic tumor was estimated to determine solid tumor volume (STV) for the STV/HV ratio. RESULTS: Twenty percent of sonograms with STV/HV <1 and 97.3% with STV/HV >1 were associated with 1 or more abnormal sonographic signs (p = 0.000). Overall mortality was 11/27 (41%). There was no mortality in fetuses with a ratio of <1, while 11/18 (61%) of fetuses with ratio >1 died (p = 0.003). CONCLUSION: The STV/HV ratio may be used to identify fetuses with a high risk of a poor outcome due to high-output cardiac failure and hydrops, and may help guide management.
Subject(s)
Sacrococcygeal Region/pathology , Teratoma/pathology , Cohort Studies , Humans , Hydrops Fetalis/diagnostic imaging , Hydrops Fetalis/epidemiology , Incidence , Prognosis , Sacrococcygeal Region/diagnostic imaging , Teratoma/complications , Teratoma/diagnostic imaging , Ultrasonography, PrenatalABSTRACT
We report a case of prenatally diagnosed chromosome 7q intermediate interstitial deletion with the aid of first-trimester Down's syndrome (DS) screening. After detection of a significantly diminished maternal serum pregnancy-associated plasma protein A and correspondingly high DS risk, the pregnant woman underwent amniocentesis for fetal chromosomal analysis. Amniocytes revealed a 46,XY,del(7) (q21.2q31.1) karyotype and 21 weeks' sonography revealed fetal growth restriction, elevated nuchal fold thickness and cardiomegaly. After therapeutic induction at 22 weeks of gestation, a 310-gram male fetus was born with multiple gross abnormalities including hypertelorism, wide nasal bridge, low-set ears, cleft palate, prominent cheeks, prominent nuchal skin, simian crease and postaxial polydactyly. We review the associated prenatal screening findings, the sonographic profile and phenotypical features associated with chromosome 7q intermediate interstitial deletion.
Subject(s)
Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 7 , Genetic Testing/methods , Prenatal Diagnosis/methods , Abortion, Induced , Adult , Chromosome Deletion , Down Syndrome/diagnosis , Down Syndrome/genetics , Female , Humans , Male , Pregnancy , Pregnancy Trimester, FirstABSTRACT
BACKGROUND/PURPOSE: Surgical intervention that improves pancreatic ductal drainage is a reasonable treatment strategy for recurrent pancreatitis in children. METHODS: This study was approved by the Committee on Human Research (San Francisco, CA). A retrospective chart review was performed on children aged 0 to 17 years given the International Classification of Diseases, Ninth Revision coding diagnosis of chronic pancreatitis who underwent surgical intervention from 1981 to 2005. RESULTS: From 1981 to 2005, 32 children were treated for the diagnosis of chronic pancreatitis. The etiologies were obstructive (n = 13), idiopathic (n = 10), hereditary (n = 6), medications (n = 2), and infection (n = 1). Fifteen patients underwent 17 operations for chronic pancreatitis, including Puestow (n = 9), cystenterostomy (n = 2), Whipple (n = 1), distal pancreatectomy (n = 1), Frey (n = 1), DuVal (n = 1), excision of enteric duplication cyst (n = 1), and pancreatic ductal dilation (n = 1). The mean age at presentation of patients undergoing surgery was 6.0 +/- 4.1 years (mean +/- SD). The mean time from presentation to operation was 3.3 +/- 3.3 years. There were no deaths after surgical intervention. Of 15 patients, 2 (13%) required rehospitalization within 90 days of surgery, one for bowel obstruction, the other for splenic infarction. The median length of stay postoperatively was 8 days (range, 5-66 days). CONCLUSIONS: Chronic pancreatitis in children differs markedly in etiology when compared with adults. In most cases seen in our institution, chronic pancreatitis resulted from ineffective ductal drainage. These disorders are amenable to surgical decompression, which, ultimately, can prevent disease recurrence.
Subject(s)
Pancreatitis, Chronic/surgery , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Pancreatitis, Chronic/etiology , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: The natural history of certain prenatally diagnosed masses is well known. Large thoracic mass lesions can evolve one of 2 ways, either to regress and cause minimal morbidity, or to progress and enlarge, often resulting in hydropic changes in the fetus. This nonimmune hydrops carries a dismal prognosis, with nearly all fetuses expiring before or shortly after birth. However, hydrops associated with fetal mass lesions can be halted and even reversed with fetal intervention and treatment of the underlying defect. We examined our patients with fetal mass lesions to evaluate survival after intervention. METHODS: Institutional approval was obtained by the Committee on Human Research. A retrospective review was performed of 294 fetuses evaluated over 15 years with large mass lesions. All patients were evaluated for evidence of fetal hydrops using ultrasound criteria. Patients were divided according to type of intervention. Primary outcome measure was 30-day survival after birth. RESULTS: (1) Patients without fetal hydrops did not undergo fetal intervention and survived to 30 days after birth (167/172, 97%). (2) Patients with fetal mass lesions that developed hydrops fared poorly with no intervention (1/33 survival, 3%), whereas fetuses undergoing prenatal intervention fared much better (15/30 open, 50%; 3/10 percutaneous, 30%). (3) Four patients with hydropic congenital cystic adenomatoid malformation (n = 3) or pulmonary sequestration (n = 1) received steroids in preparation for surgery but underwent no intervention, and the patients survived the neonatal period. CONCLUSION: Fetuses with prenatal diagnoses of masses not associated with hydrops have excellent prognosis with survival higher than 95%. Nonimmune hydrops associated with prenatal diagnosis of a fetal mass is a devastating complication with less than 5% survival. Open resection of a mass causing hydrops resulted in 50% survival, with reversal of hydrops in a group with near-uniform fatality. Further investigation is warranted regarding the use of minimally invasive prenatal therapies including steroid administration for hydropic fetuses.
Subject(s)
Edema/therapy , Fetal Therapies/methods , Neoplasms/therapy , Edema/diagnostic imaging , Female , Humans , Neoplasms/chemistry , Pregnancy , Retrospective Studies , Survival Analysis , Treatment Outcome , UltrasonographyABSTRACT
PURPOSE: The sequelae of congenital diaphragmatic hernia (CDH) continue well beyond the perinatal period. Up to 50% of these patients have subsequent recurrent herniation or small bowel obstruction (SBO). A recent trend has been toward the use of bioactive prosthetic materials. We reviewed different patch closure techniques used for CDH repair at our institution and their association with these sequelae. METHODS: A retrospective review was performed of 152 records for patients with CDH. Newborns that underwent patch repair for CDH and survived for at least 30 days were included in the analysis. Primary outcomes evaluated were recurrent herniation and SBO. Two types of prostheses were examined, Gore-Tex, an artificial material, and Surgisis, a bioactive material. RESULTS: Twelve (44%) of 27 patients who had Surgisis repair had recurrent herniation. Seventeen (38%) of 45 patients who had a Gore-Tex repair had recurrent herniation. Two additional patients in each group presented with SBO. No significant difference in recurrent herniation rates was observed (P > .5). The time to recurrence was similar in both groups (log-rank, P = .75), with most recurrences (92% Surgisis, 76% Gore-Tex) occurring in the first year. CONCLUSION: The rates of recurrent herniation and SBO after neonatal prosthetic patch repair of CDH were similar regardless of the prosthetic material used (Surgisis or Gore-Tex).