deamino-arginine-vasopressin and Inflammation

There are still many controversial aspects regarding which method is best for managing organ donors to prevent, lessen, or even reverse the organ alterations associated with brain death. Fundamental aspects are the management of an adequate perfusion pressure, hormone restoration, and opposition of the inflammatory state associated with brain death. Once volume has been normalized, it is necessary to administer vasoactive drugs, including catecholamines to re-establish the loss of sympathetic tone at the vascular and myocardial level. It is impossible to define the ideal or maximal catecholamine dose because it depends on the donor's vascular tone, vascular reactivity, and pharmacokinetic variability characteristic of critical patients, particularly organ donors. To control early onset of diabetes insipidus, it is necessary to administer desmopressin. At present there are insufficient clinical studies to show the usefulness of triiodothyronine. Furthermore, due to its limited availability, elevated cost, and probable side effects, the use of this hormone is not justified. More importance is being given to the negative influence of the inflammatory state associated with brain death, which has repercussions on organ viability and probably influences the prevalence of rejection episodes. Meanwhile in organ donor management, we recommend the use of 15 mg/kg of methylprednisolone as soon as possible. Contrary to triiodothyronine, the potential benefit of its immunomodulatory effects, its low cost, and the absence of major side effects justify this recommendation.

Topics: Anti-Inflammatory Agents; Brain; Brain Death; Deamino Arginine Vasopressin; Humans; Hypothalamo-Hypophyseal System; Inflammation; Tissue Donors; Triiodothyronine

Topics: Adrenocorticotropic Hormone; Anabolic Agents; Androgens; Clofibrate; Coronary Disease; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Fibrinolysis; Fibrinolytic Agents; Glucocorticoids; Humans; Inflammation; Male; Metformin; Phenformin; Plasminogen Activators; Postoperative Complications; Sulfonylurea Compounds; Thromboembolism; Thrombophlebitis; Vascular Diseases

Platelet sequestration, inflammation, and inappropriate coagulation cascade activation are prominent in liver xenotransplant models and are associated with poor outcomes. Here, we evaluate a cassette of six additional genetic modifications to reduce anti-pig antibody binding (α-1,3-galactosyl transferase knockout [GalTKO]) and target coagulation dysregulation (human endothelial protein C receptor [hEPRC] and thrombomodulin [hTBM]), complement pathway regulation (human membrane cofactor protein, hCD46), inflammation heme oxygenase 1 [hHO-1]), and a self-recognition receptor (integrin-associated protein [hCD47]), as well as donor pharmacologic treatments designed to blunt these phenomena.. Livers from GaltKO.hCD46 pigs ("2-gene," n = 3) and GalTKO.hCD46 pigs also transgenic for hEPRC, hTBM, hCD47, and hHO-1 ("6-gene," n = 4) were perfused ex vivo with whole human blood. Six-gene pigs were additionally pretreated with desmopressin (DDAVP) and clodronate liposomes to deplete vWF and kupffer cells, respectively.. The average perfusion times increased from 304 (±148) min in the 2-gene group to 856 (±61) min in the 6-gene group (p = .010). The average heparin administration was decreased from 8837 U/h in the 2-gene to 1354 U/h in the 6-gene group (p = .047). Platelet sequestration tended to be delayed in the 6-gene group (p = .070), while thromboxane B2 (TXB2, a platelet activation marker) levels were lower over the first hour (p = .044) (401 ± 124 vs. 2048 ± 712 at 60 min). Thrombin production as measured by F1+2 levels tended to be lower in the 6-gene group (p = .058).. The combination of the hEPCR.hTBM.hCD47.hHO-1 cassette along with donor pig DDAVP and clodronate liposome pretreatment was associated with prolonged function of xenoperfused livers, reduced coagulation pathway perturbations, and decreased TXB2 elaboration, and reflects significant progress to modulate liver xenograft injury in a pig to human model.

Topics: Animals; Animals, Genetically Modified; Clodronic Acid; Deamino Arginine Vasopressin; Graft Survival; Heme Oxygenase-1; Humans; Inflammation; Liver; Perfusion; Swine; Thrombocytopenia; Transplantation, Heterologous

Topics: Colorectal Neoplasms; Deamino Arginine Vasopressin; Hepatectomy; Humans; Inflammation; Liver Neoplasms; Prognosis

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

Two young female patients presented with polyuria and polydipsia. In one patient we additionally found idiopathic vitiligo, there were no relevant previous diseases. The gynaecological history was unremarkable.. In both cases a water deprivation test confirmed the diagnosis of central diabetes insipidus, the MRI investigation of the pituitary region showed a prominent and thickened pituitary stalk.. After exclusion of a systemic granulomatous inflammation we diagnosed an autoimmune hypophysitis based on the typical morphological lesions of the pituitary gland and stalk. TREATMENT AND FOLLOW-UP: High-dose glucocorticoid therapy was without any beneficial effect on the central diabetes insipidus. Desmopressin treatment was initiated and led to a normalization of the pre-existing polyuria and polydipsia.. Autoimmune hypophysitis is a very rare disease and the diagnosis is mostly achieved by excluding other causes. Systematic evaluations on large patient cohorts are lacking in the literature with respect to diagnostic procedures, therapy and outcome, the existing knowledge and experience is largely based on case reports. For this reason it appears desirable to create a central register to collect and to evaluate the course of disease in patients with autoimmune hypophysitis.

Topics: Adult; Antidiuretic Agents; Autoimmune Diseases; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Female; Humans; Inflammation; Magnetic Resonance Imaging; Pituitary Diseases; Pituitary Gland; Polyuria; Thirst

We reported 4 cases of lymphocytic infundibuloneurohypophysitis. All four patients had diabetes insipidus as initial symptoms without anterior pituitary dysfunction. All patients showed pituitary stalk swelling and two patients showed enlargement of the pituitary gland. No patients were operated on for a histological diagnosis. No patients received corticosteroid treatment for this pathology. The mean follow-up period was 36 months. The diabetes insipidus continued in all cases, but radiological findings showed improvement in all cases. In one case, adrenal insufficiency occurred after 10 months, but had disappeared 6 months later. We think lymphocytic infundibuloneurohypophysitis can be diagnosed without histological examinations and can be treated conservatively without corticosteroid treatment. It seems to be a self-limiting disease. This disease can be distinguished from lymphocytic adenohypophysitis, but in some cases, both the anterior and posterior pituitary glands are invaded, and in this situation lymphocytic hypophysitis may be an appropriate name. Even if the initial symptom is diabetes insipidus, careful follow-up is needed for the duration of the disease.

Topics: Aged; Chronic Disease; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Inflammation; Lymphocytes; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Diseases; Pituitary Gland

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