The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Apr 2013
ReviewClinical review: the use of vaptans in clinical endocrinology.
Hyponatremia is the most common electrolyte disorder encountered in clinical practice and represents a clinical, social, and economic burden. Conventional treatments of hyponatremia present some pitfalls, such as suboptimal efficacy, risk of overly rapid correction, and adverse effects. Vasopressin receptor antagonists, known as vaptans, represent a new and interesting class of drugs for the treatment of the euvolemic and hypervolemic forms of hyponatremia. ⋯ Vaptans can be considered a new effective tool for the treatment of euvolemic and hypervolemic hyponatremia. Nevertheless, more comparative research of vaptans vs other therapies on clinical grounds is needed to more accurately assess the value of these drugs in the treatment of hyponatremia.
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J. Clin. Endocrinol. Metab. · Apr 2013
ReviewEndocrine side effects induced by immune checkpoint inhibitors.
In recent years, progress has been made in cancer immunotherapy by the development of drugs acting as modulators of immune checkpoint proteins, such as the cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death-1 (PD-1), two co-inhibitory receptors that are expressed on T cells upon activation. These molecules play crucial roles in maintaining immune homeostasis by down-regulating T-cell signaling, thereby preventing unbridled T-cell proliferation while maintaining tolerance to self-antigens, such as tumor-associated antigens. CTLA4 blockade through systemic administration of the CTLA4-blocking antibody ipilimumab was shown to confer significant survival benefit and prolonged stable disease in patients affected by advanced cutaneous melanoma. Other immune checkpoint inhibitors are under clinical evaluation. However, immune checkpoint blockade can lead to the breaking of immune self-tolerance, thereby inducing a novel syndrome of autoimmune/autoinflammatory side effects, designated as "immune-related adverse events," mainly including rash, colitis, hepatitis, and endocrinopathies. ⋯ Although reports of endocrine side effects caused by cancer immune therapy are abundant, their exact prevalence and mechanism are unclear. Well-designed correlative studies oriented to finding and validating predictive factors of autoimmune toxicity are urgently needed.
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J. Clin. Endocrinol. Metab. · Apr 2013
Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance.
Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. ⋯ Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.