Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interactions of the integrins alpha(4)beta(7) with its cognate ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) play a crucial role in the development of mucosa-associated lymphoid organs, in the generation of mucosal immune responses, and in diverse pathological processes such as chronic inflammatory bowel disease and type I diabetes. Using a previously developed spatial screening technique we describe the development of potent and selective alpha(4)beta(7) integrin antagonists based on the domain 1 Leu-Asp-Thr (LDT) sequence of MAdCAM-1 that is essential for alpha(4)beta(7) integrin binding. A library of homodetic cyclic penta- and hexapeptides was synthesized presenting the pharmacophoric LDT-sequence in different conformations. The cyclic hexapeptide P10 cyclo(Leu-Asp-Thr-Ala-D-Pro-Ala) inhibits alpha(4)beta(7) integrin mediated cell adhesion to MAdCAM-1 effectively. Further optimization of the lead structure P10 resulted in cyclic hexapeptides with enhanced activity. The compounds P25 cyclo(Leu-Asp-Thr-Ala-D-Pro-Phe), P28 cyclo(Leu-Asp-Thr-Asp-D-Pro-Phe), P29 cyclo(Leu-Asp-Thr-Asp-D-Pro-His), and P30 cyclo(Leu-Asp-Thr-Asp-D-Pro-Tyr) strongly inhibited alpha(4)beta(7) integrin mediated cell adhesion to MAdCAM-1, but they did not affect binding of the closely related alpha(4)beta(1) integrin to VCAM-1.
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PMID:Design and synthesis of potent and selective alpha(4)beta(7) integrin antagonists. 1147 12

Non-classic congenital adrenal hyperplasia (NCAH) is a rare cause of hirsutism and it results from a defect in the biosynthetic pathway of cortisol and/or aldosterone. 250 microg ACTH test (SDT) is used in the diagnosis of this disease. Our aim was to investigate the responses of 11-deoxycortisol to 1microg ACTH (LDT) test in women with NCAH due to 11-beta hydroxylase (11- beta OH) deficiency and to compare them with the values obtained after SDT in the patients and in the control subjects. Eleven patients with NCAH due to 11- beta OH deficiency and 15 control subjects were involved in the study. The main complaint of the patients with NCAH was hirsutism and the diagnosis was made if the adrenal 11-deoxycortisol response to SDT exceed threefold the 95th percentile of controls. ACTH stimulation tests were carried out consecutively by using 250 microg and 1 microg intravenous ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0,30 and 60 min. Peak cortisol, 17-hydroxyprogesterone (17-OHP) and DHEAS responses were similar in LDT and SDT while 11-deoxycortisol responses to LDT (15.7 +/- 1.8 nmol/L) were significantly (p < 0.005) lower than the results obtained after SDT (76.3 +/- 21.4 nmol/L) in women with 11- beta OH deficiency. Peak cortisol and 17-OHP responses to LDT in patients and control subjects were similar. Peak 11-deoxycortisol responses to LDT were significantly (p < 0.05) higher in NCAH patients (15.7 +/- 1.8 nmol/L) than in the control subjects (6.5 +/- 0.8 nmol/L). However, in LDT, all patients had peak 11-deoxycortisol level lower than threefold the 95th percentile (25.8 nmol/L) of controls. This study represents the first demonstration that LDT gives similar cortisol but not 11-deoxycortisol responses to SDT in patients with 11- beta OH deficiency. This study also showed that LDT can not replace SDT in every clinical situation.
Exp Clin Endocrinol Diabetes 2002 Nov
PMID:The value of low dose (1 microg) ACTH stimulation test in the investigation of non-classic adrenal hyperplasia due to 11beta-hydroxylase deficiency. 1251 47

Induction of hormesis and adaptive response by low-dose radiation (LDR) has been extensively indicated. Adaptive response induced by LDR was not only resistant to damage caused by a subsequently high-dose radiation, but also cross-resistant to other non-radiation challenges, such as chemicals. Mechanisms by which LDR induces the preventive effect on radiation- or chemical-induced tissue damage include induced or up-regulated expression of protective proteins, such as heat shock proteins and antioxidants. Since oxidative damage to tissues is a major pathogenesis of many human diseases including diabetes, this review will summarize the available data with an emphasis of the preventive effect of LDR on the development of diabetes and the therapeutic effect of LDR on diabetic cardiovascular complications. The available data indicated that pre-exposure of mice to LDR reduced the incidence of alloxan-induced diabetes, and also delayed the onset of hyperglycaemia in diabetes-prone non-obese diabetic mice. Experiments with animals indicated the effectively therapeutic effect of low-intensity or power laser (LIL or LPL) radiation on skin wound healing, which has stimulated clinical use of LIL to cure skin ulcer in diabetic patients. Mechanisms by which LDR prevents diabetes, though are unclear now, may include the induction of pancreatic antioxidants to prevent beta cell from oxidative damage and immunomodulation to preserve pancreatic function. For LIL therapeutic effect on diabetic wound healing, mechanisms may include its antioxidant action, immunomodulation, cell proliferation stimulation as well as improvement of systemic and wound-regional microcirculation. Therefore, although only a few studies indicating LDR prevention of the development of diabetes, many studies have demonstrated LDR, specifically LIL, therapeutic effectiveness of diabetic wound healing. These preliminary results are really encouraging for us to further pursue the clinical implication of LDT to diabetes-related areas.
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PMID:Low-dose radiation and its clinical implications: diabetes. 1848 Jan 38

Background: Thalassemia Major (TM) is a complex pathology that needs a highly skilled approach. Endocrine comorbidities are nowadays the most important complications, including hypogonadism, hypothyroidism, diabetes mellitus, and bone diseases. Recent works stated that there could be a relevant prevalence of adrenal insufficiency (AI) present in TM, and this fact may become crucial, especially in case of major stressful events. Aim: Test the reliability of the standard test to diagnose AI in a group of TM and correlate it with clinical, hematological, and radiological data. Methods: We evaluated endocrine damages and the efficacy of iron chelation therapy in 102 patients affected by TM. AI was assessed by tetracosactide (Synacthen) 1 mcg iv (low-dose test, LDT) stimulation test. Patients with a subnormal response (peak cortisol < 500 nmol/L) were followed up to 5 years to check the symptoms and signs of AI. Results: We found AI in 13.7% of the population studied. We did not find any correlation between AI and all data evaluated. Only female gender seems to be a protective factor. A follow up of the patients affected by AI showed no signs of adrenal crisis, in spite of no replacement therapy. Conclusions: Our study shows a relevant prevalence of AI in TM, especially in males. The absence of an adrenal crisis, in spite of no replacement therapy, during the long-term follow up, seems to underline that current methods to evaluate AI, in TM, should consider a different and specific diagnostic test or different cut off for diagnosis.
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PMID:New Insights and Methods in the Approach to Thalassemia Major: The Lesson From the Case of Adrenal Insufficiency. 3206 67