RESUMO
Spexin (SPX) is a novel adipokine related to many metabolic effects, such as gastrointestinal movements, insulin and glucose homeostasis, lipid metabolism and energy balance. This study evaluates the role of SPX in the improvement of the metabolic and inflammatory profile in fructose-rich-diet obese mice. Adult Swiss mice were supplemented or not with fructose (20% in tap water, FRD and CTR, respectively) for 10 weeks. The last ten days, mice were treated or not with SPX (ip. 29 µg/Kg/day, FRD-SPX and CTR-SPX, respectively). A positive correlation was observed between body weight prior to treatment and weight loss after SPX challenge. Moreover, plasma and liver triglycerides and adipose tissue (AT) features (mass, adipocyte hypertrophy, mRNA of leptin) were improved. SPX also induced a reduction in epididymal AT (EAT) expression of TNFα, IL1ß and IL6 and an improvement in IL10 and CD206. M1 macrophages in EAT, principally the Ly6C- populations (M1a and M1b), were decreased. Adipocytes from FRD-SPX mice induced less macrophage activation (IL6, mRNA and secretion) than FRD after overnight co-culture with the monocyte cell line (RAW264.7) in stimulated conditions (M1 activation, LPS 100 ng/mL). Finally, in vitro, monocytes pre-incubated with SPX and stimulated with LPS showed decreased inflammatory mRNA markers compared to monocytes with LPS alone. In conclusion, SPX decreased body weight and improved the metabolic profile and adipocyte hypertrophy. Inflammatory Ly6C- macrophages decreased, together with inflammatory marker expression. In vitro studies demonstrate that SPX induced a decrease in M1 macrophage polarization directly or through mature adipocytes.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Ativação de Macrófagos , Macrófagos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Hormônios Peptídicos/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Células Cultivadas , Interleucinas/genética , Interleucinas/metabolismo , Macrófagos/imunologia , Masculino , Camundongos , Hormônios Peptídicos/uso terapêutico , Células RAW 264.7 , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Aesporotricose é uma micose subcutânea causada pelos fungos do complexo Sporothrix schenckii. Essa doença afeta homens e animais, sendo particularmente grave em gatos. A infecção ocorre principalmente pela inoculação traumática do fungo, ou seja, por meio de arranhadura e mordeduras de animais infectados. Doenças imunossupressoras como a FeLV e a dificuldade na administração dos medicamentos são fatores que complicam o prognóstico desses pacientes. O objetivo do presente artigo é relatar o manejo terapêutico da esporotricose em um gato soropositivo para FeLV, que levou à regressão das lesões e a uma importante melhora clínica do paciente.(AU)
Sporotrichosis is a subcutaneous mycosis caused by the fungi of the Sporothrix schencki complex. The disease affects men and animals and is particularly severe in cats. The infection is typically acquired by traumatic inoculation of the fungus through scratches and bites from infected animals. Prognosis is worse in patients with immunodepressive diseases such as FeLV, and when administration of treatment is challenging. We report the therapeutic management of sporotrichosis in a cat seropositive for FeLV. Treatment resulted in regression of lesions and marked improvement of clinical signs.(AU)
La esporotricosis es una micosis subcutánea provocada por hongos del complejo Sporothrix schencki. Esta enfermedad puede afectar tanto al hombre como a los animales, siendo particularmente grave en los gatos. La infección se produce en general por inoculación traumática del hongo, es decir, mediante arafíazos y mordeduras de animales infectados. Entre los factores que complican el pronóstico de estos pacientes pueden contarse, por un lado a las enfermedades inmunosupresoras como la FeLV, y por otro la dificultad que existe para la administración de medicamentos en esta especie. EI objetivo del presente trabajo es relatar el manejo terapéutico de un gato con esporotricosis que era positivo para FeLV, en el cual se consiguió la regresión de las lesiones y una importante mejoría clínica del paciente.(AU)
Assuntos
Animais , Gatos , Esporotricose/veterinária , Vírus da Leucemia Felina , Sporothrix , Hormônios Peptídicos/uso terapêutico , Itraconazol , ZoonosesRESUMO
Aesporotricose é uma micose subcutânea causada pelos fungos do complexo Sporothrix schenckii. Essa doença afeta homens e animais, sendo particularmente grave em gatos. A infecção ocorre principalmente pela inoculação traumática do fungo, ou seja, por meio de arranhadura e mordeduras de animais infectados. Doenças imunossupressoras como a FeLV e a dificuldade na administração dos medicamentos são fatores que complicam o prognóstico desses pacientes. O objetivo do presente artigo é relatar o manejo terapêutico da esporotricose em um gato soropositivo para FeLV, que levou à regressão das lesões e a uma importante melhora clínica do paciente.
Sporotrichosis is a subcutaneous mycosis caused by the fungi of the Sporothrix schencki complex. The disease affects men and animals and is particularly severe in cats. The infection is typically acquired by traumatic inoculation of the fungus through scratches and bites from infected animals. Prognosis is worse in patients with immunodepressive diseases such as FeLV, and when administration of treatment is challenging. We report the therapeutic management of sporotrichosis in a cat seropositive for FeLV. Treatment resulted in regression of lesions and marked improvement of clinical signs.
La esporotricosis es una micosis subcutánea provocada por hongos del complejo Sporothrix schencki. Esta enfermedad puede afectar tanto al hombre como a los animales, siendo particularmente grave en los gatos. La infección se produce en general por inoculación traumática del hongo, es decir, mediante arafíazos y mordeduras de animales infectados. Entre los factores que complican el pronóstico de estos pacientes pueden contarse, por un lado a las enfermedades inmunosupresoras como la FeLV, y por otro la dificultad que existe para la administración de medicamentos en esta especie. EI objetivo del presente trabajo es relatar el manejo terapéutico de un gato con esporotricosis que era positivo para FeLV, en el cual se consiguió la regresión de las lesiones y una importante mejoría clínica del paciente.
Assuntos
Animais , Gatos , Esporotricose/veterinária , Hormônios Peptídicos/uso terapêutico , Sporothrix , Vírus da Leucemia Felina , Itraconazol , ZoonosesRESUMO
Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides being produced in peripheral tissues and acting as an autocrine and paracrine signal, melatonin is centrally synthetized by a neuroendocrine organ, the pineal gland. Independently of the considered species, pineal hormone melatonin is always produced during the night and its production and secretory episode duration are directly dependent on the length of the night. As its production is tightly linked to the light/dark cycle, melatonin main hormonal systemic integrative action is to coordinate behavioral and physiological adaptations to the environmental geophysical day and season. The circadian signal is dependent on its daily production regularity, on the contrast between day and night concentrations, and on specially developed ways of action. During its daily secretory episode, melatonin coordinates the night adaptive physiology through immediate effects and primes the day adaptive responses through prospective effects that will only appear at daytime, when melatonin is absent. Similarly, the annual history of the daily melatonin secretory episode duration primes the central nervous/endocrine system to the seasons to come. Remarkably, maternal melatonin programs the fetuses' behavior and physiology to cope with the environmental light/dark cycle and season after birth. These unique ways of action turn melatonin into a biological time-domain-acting molecule. The present review focuses on the above considerations, proposes a putative classification of clinical melatonin dysfunctions, and discusses general guidelines to the therapeutic use of melatonin.
Assuntos
Melatonina/metabolismo , Melatonina/uso terapêutico , Hormônios Peptídicos/metabolismo , Hormônios Peptídicos/uso terapêutico , Animais , HumanosRESUMO
El estudio de los desórdenes genéticos del metabolismo del hierro, la identificación de sus transportadores y el descubrimiento de la hepcidina, hormona reguladora de la homeostasia del hierro, han contribuido grandemente a aumentar los conocimientos sobre este metabolismo y han cambiado sustancialmente la visión sobre las enfermedades relacionadas con alteraciones del metabolismo férrico. En la última década, no solo se han esclarecido elementos de la patogénesis de estas enfermedades, sino que ya se vislumbran aplicaciones terapéuticas de estos avances. Así, ya se habla de una nueva era basada en el tratamiento de los desórdenes de la homeostasia del hierro a través de la modulación de la hepcidina
The study of genetic disorders of iron metabolism, identification of transporters and the discovery of hepcidin- a hormone regulating iron homeostasis- have contributed greatly to increase awareness of this metabolism. Substantially, the vision on diseases related to disorders of iron metabolism has been changed. In the last decade, elements of the pathogenesis of these diseases have not only been clarified, but therapeutic applications of these advances are looming. Thus, there are expectations of a new era based on the treatment of iron homeostasis disorders through hepcidin modulation
Assuntos
Humanos , Masculino , Feminino , Ferro/sangue , Homeostase/fisiologia , Proteínas Reguladoras de Ferro , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/prevenção & controle , Hormônios Peptídicos/uso terapêuticoRESUMO
Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/fisiologia , Hormônio do Crescimento Humano/fisiologia , Hormônios Peptídicos/metabolismo , Receptores Acoplados a Proteínas G/fisiologia , Grelina , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Oligopeptídeos/fisiologia , Hormônios Peptídicos/fisiologia , Hormônios Peptídicos/uso terapêutico , Receptores de GrelinaRESUMO
Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides.