Tipos, Causas y Manifestaciones Clínicas de la Diabetes Insípida: Una Visión Integral

Diabetes insipidus is a rare condition that affects the body's fluid balance due to a decrease in the production or action of the antidiuretic hormone (ADH). There are two main types of diabetes insipidus: central diabetes insipidus and nephrogenic diabetes insipidus. Central diabetes insipidus is caused by a deficiency in the production or release of ADH by the pituitary gland, while nephrogenic diabetes insipidus is due to renal resistance to the action of ADH. The causes of diabetes insipidus can vary and may include tumors, head injuries, infections, kidney diseases, or medications. The most common symptoms and clinical manifestations of diabetes insipidus include polyuria, polydipsia, nocturia, and dehydration. Additionally, electrolyte imbalances and sleep disorders may be present in some patients. This article summarizes the manifestations of diabetes insipidus and can contribute to providing information for future research.La diabetes insípida es una enfermedad poco común que afecta el equilibrio de líquidos en el cuerpo debido a la disminución en la producción o acción de la hormona antidiurética (ADH). Se pueden distinguir dos tipos principales de diabetes insípida: la diabetes insípida central y la diabetes insípida nefrogénica. La diabetes insípida central es causada por un déficit en la producción o liberación de ADH por parte de la glándula pituitaria y la diabetes insípida nefrogénica se debe a la resistencia renal a la acción de la ADH. Las causas de la diabetes insípida pueden variar, puede ser causada por tumores, traumatismos craneales, infecciones, enfermedades renales o medicamentos. Los síntomas y manifestaciones clínicas más comunes de la diabetes insípida incluyen poliuria, polidipsia, nocturia y deshidratación, además, los desequilibrios electrolíticos y los trastornos del sueño pueden estar presentes en algunos pacientes. Este artículo resume las manifestaciones en que puede presentarse la diabetes insípida y con ello, puede contribuir en proporcionar información a futuras investigaciones

Small-Molecule Activators of Insulin-Degrading Enzyme Discovered through High-Throughput Compound Screening

Background: Hypocatabolism of the amyloid β-protein (Aβ) by insulin-degrading enzyme (IDE) is implicated in the pathogenesis of Alzheimer disease (AD), making pharmacological activation of IDE an attractive therapeutic strategy. However, it has not been established whether the proteolytic activity of IDE can be enhanced by drug-like compounds. Methodology/Principal Findings: Based on the finding that ATP and other nucleotide polyphosphates modulate IDE activity at physiological concentrations, we conducted parallel high-throughput screening campaigns in the absence or presence of ATP and identified two compounds—designated Ia1 and Ia2—that significantly stimulate IDE proteolytic activity. Both compounds were found to interfere with the crosslinking of a photoaffinity ATP analogue to IDE, suggesting that they interact with a bona fide ATP-binding domain within IDE. Unexpectedly, we observed highly synergistic activation effects when the activity of Ia1 or Ia2 was tested in the presence of ATP, a finding that has implications for the mechanisms underlying ATP-mediated activation of IDE. Notably, Ia1 and Ia2 activated the degradation of Aβ by ∼700% and ∼400%, respectively, albeit only when Aβ was presented in a mixture also containing shorter substrates. Conclusions/Significance: This study describes the first examples of synthetic small-molecule activators of IDE, showing that pharmacological activation of this important protease with drug-like compounds is achievable. These novel activators help to establish the putative ATP-binding domain as a key modulator of IDE proteolytic activity and offer new insights into the modulatory action of ATP. Several larger lessons abstracted from this screen will help inform the design of future screening campaigns and facilitate the eventual development of IDE activators with therapeutic utility

Identification of the Allosteric Regulatory Site of Insulysin

Background: Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Ab peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP.Principal Findings: the crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. in addition, changes in the dimer interface suggest a basis for communication between subunits.Conclusions/Significance: Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.United States Public Health ServicesUniv Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USAUniv Kentucky, Struct Biol Ctr, Lexington, KY USAUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUnited States Public Health Services: NS38041United States Public Health Services: DA02243United States Public Health Services: DA016176United States Public Health Services: P20 RR20171United States Public Health Services: T32 DA016176Web of Scienc

Relacion historica de las reales fiestas que la muy noble y muy leal ciudad de Santiago de los Caballeros de Guathemala celebró desde el dia ocho de abril de 1747 años en la proclamacion de Ntro. Cathólico Monarca,el Sr. D. Fernando VI, Rey de España y de las Indias (que Dios guarde)

Port. orladaSign.: [@]>221