ABSTRACT
Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca2+ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca2+ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca2+ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (Dmit) and energy availability, is unclear. Therefore, in a rat model of Hypo, we aimed to characterize systolic and diastolic Ca2+ signaling, T-T remodeling, Dmit, citrate synthase (CS) activity and high-energy phosphate metabolites (ATP and phosphocreatine). We confirmed a decrease in SERCA/PLB (59%), which slowed SERCA activity (48%), reduced SR Ca2+ (19%) and blunted Ca2+ transient amplitude (41%). Moreover, assessing the rate of SR Ca2+ release (dRel/dt), we found that early and maximum dRel/dt decreased, and this correlated with staggered Ca2+ transients. However, dRel/dt persisted during Ca2+ transient relaxation due to abundant late Ca2+ sparks. Isoproterenol significantly up-regulated systolic Ca2+ cycling. T-T were unchanged, hence, cannot explain staggered Ca2+ transients and altered dRel/dt. Therefore, we suggest that these might be caused by RyR2 clusters desynchronization, due to diminished Ca2+-dependent sensitivity of RyR2, which also caused a decrease in diastolic SR Ca2+ leak. Furthermore, Dmit was unchanged and CS activity slightly decreased (14%), however, the ratio phosphocreatine/ATP did not change, therefore, energy deficiency cannot account for Ca2+ and contractility dysregulation. We conclude that decreased SR Ca2+, due to slower SERCA, disrupts systolic RyR2 synchronization, and this underlies CD.
Subject(s)
Hypothyroidism/physiopathology , Myocardial Contraction/physiology , Myocytes, Cardiac/pathology , Animals , Atrophy , Calcium/metabolism , Calcium Signaling/drug effects , Citrate (si)-Synthase/metabolism , Disease Models, Animal , Heart Ventricles/drug effects , Heart Ventricles/pathology , Hypothyroidism/blood , Male , Mitochondria/drug effects , Mitochondria/metabolism , Myocardial Contraction/drug effects , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Rats, Wistar , Sarcoplasmic Reticulum/drug effects , Sarcoplasmic Reticulum/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Systole/drug effects , Thapsigargin/pharmacology , Thyroid Hormones/blood , Time FactorsABSTRACT
Pleomorphic lipoma is an uncommon variant of lipoma, which microscopically may resemble a liposarcoma. However, it is a slow-growing and well-circumscribed lesion with a benign behavior. Therefore, recognizing this entity is extremely important to perform the proper treatment. We present an additional case of pleomorphic lipoma in the face, which to our knowledge seems to be the 11th case reported in the English-language literature.
Subject(s)
Facial Neoplasms/pathology , Lipoma/pathology , Aged , Antigens, CD/analysis , Antigens, CD34/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Biopsy , Humans , Immunohistochemistry , MaleABSTRACT
This paper reports one case of primary fibrosarcoma affecting the mandible in a 41-year-old woman. Microscopically, the tumor was cellularized with an intense mitotic activity, and areas of necrosis and hemorrhage, and the cells showed immunoreactivity only for vimentin, establishing the diagnosis of primary intraosseous fibrosarcoma. The patient underwent tumor surgical resection, supraomohyoid neck dissection and mandible reconstruction with fibula flap and titanium bar. She also received post-surgical radiotherapy and is in follow up for 36 months without signs of recurrence or metastases.
Subject(s)
Fibrosarcoma/pathology , Mandibular Neoplasms/pathology , Adult , Biopsy , Female , Fibrosarcoma/surgery , Follow-Up Studies , Humans , Mandibular Neoplasms/surgery , Mitosis , Necrosis , Vimentin/analysisSubject(s)
Denture, Partial, Fixed, Resin-Bonded , Self Care , Denture Design , Humans , Male , Middle Aged , Tooth ExtractionSubject(s)
Denture, Partial, Fixed, Resin-Bonded , Self Care , Denture Design , Humans , Male , Middle Aged , Tooth ExtractionABSTRACT
Hypodontia, the congenital absence of one or a few permanent teeth, is one of the most frequent alterations of the human dentition. Although hypodontia does not represent a public health problem, it may cause both speech and masticatory dysfunction and esthetic problems. A missense mutation in the homeodomain of MSX1 gene has been associated with hypodontia of second premolars and third molars in humans. However, another study excluded this gene as causative locus for hypodontia of incisors and premolars. To further investigate the role of the MSX1 gene in human hypodontia, we analyzed the homeobox region of the MSX1 gene in 20 individuals with different patterns of familial or isolated hypodontia. The direct sequencing of PCR products did not show any polymorphisms or mutations in the human MSX1 gene. Our results indicate that inactivation of MSX1 gene in humans must have a highly selective effect on dentition, and other genes must be involved in the cause of hypodontia in humans.