deamino-arginine-vasopressin and Fibrosis

Benign prostatic hyperplasia (BPH) is a major health concern for aging men. BPH is associated with urinary voiding dysfunction and lower urinary tract symptoms (LUTS), which negatively affects quality of life. Surgical resection and medical approaches have proven effective for improving urinary flow and relieving LUTS but are not effective for all men and can produce adverse effects that require termination of the therapeutic regimen. Thus, there is a need to explore other therapeutic targets to treat BPH/LUTS. Complicating the treatment of BPH/LUTS is the lack of biomarkers to effectively identify pathobiologies contributing to BPH/LUTS or to gauge successful response to therapy. This review will briefly discuss current knowledge and will highlight new studies that illuminate the pathobiologies contributing to BPH/LUTS, potential new therapeutic strategies for successfully treating BPH/LUTS, and new approaches for better defining these pathobiologies and response to therapeutics through the development of biomarkers and phenotyping strategies.

Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Androgen Antagonists; Antidiuretic Agents; Biomarkers; Collagen; Deamino Arginine Vasopressin; Fibrosis; Humans; Lower Urinary Tract Symptoms; Male; Molecular Targeted Therapy; Myofibroblasts; Plant Extracts; Prostatic Hyperplasia

Fibrosis is a major cause of loss of renal function in autosomal dominant polycystic kidney disease (ADPKD). In this study, we examined whether vasopressin type-2 receptor (V2R) activity in cystic epithelial cells can stimulate interstitial myofibroblasts and fibrosis in ADPKD kidneys.. We treated. Our results demonstrate a novel mechanism by which cystic epithelial cells stimulate myofibroblasts in the pericystic microenvironment, leading to fibrosis in ADPKD. The V2R-YAP-CCN2 cell signaling pathway may present a potential therapeutic target for fibrosis in ADPKD.

Topics: Animals; Cell Cycle Proteins; Connective Tissue Growth Factor; Deamino Arginine Vasopressin; Extracellular Matrix; Fibrosis; Humans; Kidney; Mice; Myofibroblasts; Polycystic Kidney, Autosomal Dominant; Receptors, Vasopressin; Transcription Factors; TRPP Cation Channels

A 45-year-old man was hospitalized because of weight loss, finger tremor, thirst, polydipsia and increased urinary frequency. He was diagnosed with Graves' disease (GD) and central diabetes insipidus (CDI). Magnetic resonance imaging revealed the enlarged posterior pituitary with thickened stalk. Histological examination obtained from biopsy of the pituitary revealed lymphocytic infundibulo-neurohypophysitis. He received treatment with thiamazole (MMI) for GD and desmopressin acetate (DDAVP) for CDI. However, DDAVP administration could be discontinued as GD was gradually improved. This course indicates that not only the recovered renal response to arginine-vasopressin but also the immunomodulative effects of MMI might attribute to the improvement of polyuria.

Topics: Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Fibrosis; Graves Disease; Humans; Inflammation; Lymphocytes; Male; Methimazole; Middle Aged; Osmolar Concentration; Pituitary Gland, Posterior; Polyuria; Remission Induction; Saline Solution, Hypertonic; Thyroxine; Urine

We describe five patients with chronic inflammation of the hypophysis including three pituitary granulomas of unknown aetiology. In contrast to the previously reported cases, the involvement of neurohypophysis or hypothalamus was a distinct clinical feature in these patients. Impairment of anterior pituitary function was less prominent, while polyuria and polydipsia occurred in all cases. Enlargement of the sella turcica was absent in three and slight in two cases. CT scan and MR images demonstrated a contrast-enhanced sellar mass in all patients; abnormally thickened pituitary stalk and infundibulum with contrast-enhancement was observed in four. The fibrous tissues were removed by the transsphenoidal approach in four patients, and by the subfrontal approach in one case. In all patients, the endocrinological dysfunction was prolonged. No increase in the size of the remaining pituitary mass was demonstrated on repeated MR images in any of the patients. On histological examination, granulomatous formation was present in three samples, and multinucleated Langhans' giant cells were seen in one. The epithelioid cells and multinucleated giant cells constituting the granulomas were positive for anti-macrophage antibody. No firm laboratory or histological evidence was obtained supporting the presence of systemic disease leading to granulomas. In the other two cases, the pituitary lesions were composed of chronic inflammation tissue, and serum antipituitary antibodies were present in a patient with concurrent Hashimoto's thyroiditis. Our experiences with chronic inflammation of the hypophysis indicate that these patients are best managed by histological confirmation of the lesion followed by adequate hormonal replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Corticosterone; Deamino Arginine Vasopressin; Female; Fibrosis; Granuloma; Granuloma, Giant Cell; Humans; Inflammation; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Diseases; Pituitary Function Tests; Pituitary Gland; Postoperative Care; Thyroid Hormones; Tomography, X-Ray Computed