Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arthropathy is the major cause of morbidity in acromegaly. To feature the spinal involvement, 54 patients with active acromegaly (27 men, 27 women; age range, 21-69 yr) and 54 sex-, age-, and body mass index-matched healthy controls were enrolled in this observational analytical prospective case-control study. A questionnaire to describe onset, duration, and severity of articular symptoms; rheumatological examination, including vertebral and chest mobility, Schober test, thorax expansion, and axial radiological study; and IGF-I, GH, insulin, and glucose level measurement (baseline and after an oral glucose tolerance test) was used to investigate the prevalence of arthropathy and correlate these findings with hormonal parameters. Axial arthropathy was found in 28 patients (52%) and 12 controls (22%; chi(2) = 8.9; P = 0.003). In detail, spinal mobility was reduced in 30 patients (56%) and 10 controls (18%; chi(2) = 14.3; P < 0.0001), thoracic cage was involved in six patients (11%), alterations of spinal profile were observed in 37 patients (68%) and 15 controls (28%; chi(2) = 16.3; P < 0.0001), and increased L2 vertebra diameters were observed in 34 patients (63%) and none of the controls (chi(2) = 46.7; P < 0.0001). Narrowing and widening of L2-L3 disk space were found in 20 (37%) and seven (13%) patients, respectively. Features of diffuse idiopathic skeletal hyperostosis (DISH) were found in 11 patients (20%) and none of the controls (chi(2) = 10.1; P < 0.001). Disease duration was correlated with vertebral body height (P = 0.001) or intervertebral space height (P = 0.02), and lumbar mobility with thorax expansion (P = 0.004); DISH severity was correlated with basal (P = 0.04) and peak (P = 0.01) glucose levels after glucose load. In conclusion, chronic GH and IGF-I excess typically affects the axial skeleton with development of severe alterations of spine morphology and function until features of DISH occur. An early diagnosis of acromegaly is mandatory to reduce the severity of spine abnormalities as they were significantly higher in patients with longer disease duration.
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PMID:Acromegalic axial arthropathy: a clinical case-control study. 1476 68

It is well accepted that mortality in acromegaly is increased because of cardiovascular and respiratory diseases while neoplastic complications account less to mortality. Amongst different cardiovascular complications the most frequent is biventricular hypertrophy, which occurs independently of hypertension and metabolic complications that, in turn, aggravate the cardiomyopathy. Diastolic and systolic dysfunction develops in a variable number of patients, depending on age and disease duration. Other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis and endothelial dysfunction have been less characterized but all appear to be present in acromegaly, depicting the so called "acromegalic cardiomyopathy". The best characterized respiratory disease is the sleep apnea. Ventilatory dysfunction recognizes bony changes of thoracic cage and lung overgrowth as relevant pathogenetic factors. Earlier evidences that patients with acromegaly have an increased risk of developing malignancies have become more realistic in recent years. Most studies have reported an increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment. Malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level and are not a main cause of mortality. Bone changes are also feature of the disease. They involve theoretically all bones and, particularly, the appendicular and the axial skeleton. Patients with long-standing disease are more prone to develop degenerative changes. Control of acromegaly by surgery or pharmacotherapy, especially by somatostatin analogs, improves cardiovascular morbidity and sleep apnea. There is still no demonstration that improvement of different complications corresponds a reduction in mortality.
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PMID:Severe systemic complications of acromegaly. 1611 80

In the middle of the last century, there was a spectacular progress in the discovery, characterization and synthesis of neuropeptides. This was only possible because increasingly sophisticated analytical and isolation technology was becoming available. The pituitary lobes have become a real treasure house for the detection of different peptides, but also other glands and organs in the gastrointestinal (GI) and central nervous system (CNS) tracts have contained an ever growing list of regulatory peptides with sometimes unknown functionality. The main burning issues were to elucidate their role in physiology and, case by case and based on their structure, whether it was possible to design useful drugs for human therapy. Both issues were and are still being dealt with, and the history of somatostatin and somatostatin analogs is a good example of how such issues are being tackled successfully. In 1973, Brazeau and Guillemin's search at the Salk Institute for a GHRH in extracts of thousands of sheep hypothalami was crowned by a surprise, the discovery of a GHRH antagonist, a 14-amino acid Cystin bridge-containing peptide which they called somatostatin. This neuropetide appeared to be widely distributed in animal and human organs in the periphery and CNS, suggesting its potential regulatory functions, yet a thorough characterization of its properties due to its extremely short half-life was not possible. More insight could only be feasible with the synthesis of stable and potent analogs, a program that soon started in different research centers around the world. After having elucidated the 3-dimensional structure, the enzymatic degradation pattern and minimal chain length for biological activity of the natural hormone, the synthesis of a large number of analogs was started as early as 1974. The approach of the Sandoz team was to start with a hexapeptide lead structure Cys-Phe-DTrp-Lys-Thr-Cys and, by systematic elongation of the N and C terminals, in 1980 they managed to characterize the most stable and active analog with the following structure: H-DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr-OI-Octreotide. It was more potent in inhibiting GH in vivo compared to the native hormone. It demonstrated sufficient stability in vivo and, therefore, it was selected for clinical studies. In 1988, the first registration was obtained for treating acromegaly and carcinoid tumors. Since then, different depot preparations have been made available. Other analogs with similar structures have been also synthesized and are commercially available. The so-called targeting approach takes advantage of the presence of somatostatin receptors on different tumors. By coupling octreotide structural elements to so-called cage molecules complexing B or Y emitting isotopes, also the detection of somatostatin receptor containing tumors could be visualized and treated. The use of different somatostatin derivatives found its way since then both in basic research and in human therapy, and it is still opening new and exciting prospects.
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PMID:The history of somatostatin analogs. 1662 37