Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With regard to diabetic retinopathy, in addition to the demonstration by the DCCT study that prevention is achieved by good metabolic control, our present knowledge on physiopathology leads us to imagine three types of possible therapeutic approach; inhibition of glucotoxicity, improvement of capillary flow, blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase inhibitors can prevent cataract in diabetic or galactosemic rats. The effect of these drugs on retinopathy, evaluated in some clinical trials, remains controversial, suggesting a minor role. Aminoguanidine is an inhibitor of formation of advanced glycosylation end-products (AGE). This compound has been tested on a model of experimental retinopathy in rats. Parallel to the AGE decrease in retina, formation of microaneurysms and loss of endothelial cells in capillaries were delayed. Clinical tolerance allows human application and randomised trials will give further information on this potentially efficient drug. 2) Improvement of capillary flow This objective can be obtained by drugs inhibiting platelet aggregation or improving erythrocyte or leucocyte deformability. Clinical trials using such compounds were not very conclusive. 3) Blockade of angiogenesis Proliferation of new vessels is a rather severe stage of diabetic retinopathy. Angiogenesis is due to factors locally produced (as FGF, TGF and u-PA produced by anoxic tissues), systemic (IGF-1) or released by inflammatory reaction (IL1, TNF alpha and beta). One imagines usage of drugs which inhibit these factors and prevent angiogenesis. At the present time, two approaches have been used in proliferative retinopathy worsening despite panphotocoagulation; analogues of somatostatin and interferon alpha. The promissing results of these pilot studies have to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Outlook for the future in the treatment of diabetic retinopathy]. 752 51

Experimental arthritis induced by Freund-adjuvant administration is a model of chronic inflammation and rheumatoid arthritis associated with a decrease in pituitary growth hormone (GH) and hepatic insulin-like growth factor I (IGF-I) gene expression. Excessive nitric oxide (NO) synthesis by inducible NO synthase (iNOS) has been implicated in the pathogenesis of inflammatory illness. Moreover, NO participates in the regulation of GH secretion at both the hypothalamus and the pituitary. We have examined the role of iNOS activation in producing the changes in the GH-IGF-I axis in arthritic rats. Adult male Wistar rats received aminoguanidine or vehicle from day 20, after adjuvant or vehicle injection, until day 28. Two hours and 30 min after the last aminoguanidine injection, all rats were killed by decapitation. Arthritis increased hypothalamic expression of somatostatin mRNA while it decreased pituitary GH mRNA expression, and both effects were prevented by aminoguanidine administration. In arthritic rats, the parallel decrease in serum IGF-I, and in hepatic IGF-I content and mRNA expression, correlates with the decrease in circulating GH concentrations. Aminoguanidine administration to arthritic rats did not modify either serum GH or serum IGF-I concentrations, or hepatic IGF-I mRNA expression. However, aminoguanidine administration to control rats resulted in a decrease in serum GH concentrations and in a decrease in both hepatic IGF-I mRNA expression and serum IGF-I concentrations. These data suggest that NO mediates the arthritis-induced decrease in GH mRNA expression by acting at a hypothalamic level, but it is not involved in the decrease in hepatic IGF-I mRNA expression.
 ...
PMID:The inhibition of inducible nitric oxide synthase reverts arthritic-induced decrease in pituitary growth hormone mRNA but not in liver insulin-like growth factor I mRNA expression. 1463 80

Acute inflammation induced by endotoxin (LPS) administration inhibits insulin-like growth factor (IGF-I) and growth hormone (GH) secretion. The aim of this study was to elucidate the role of glucocorticoids and nitric oxide (NO) in the effect of LPS on hypothalamic somatostatin gene expression. Adult male Wistar rats were injected with different doses of LPS (5, 10 and 100 microg/kg). Rats received two i.p. injections of LPS (at 17:30 and 8:30 h the following day) and were killed 4 h after the second injection. LPS administration at the dose of 100 microg/kg increased the hypothalamic somatostatin mRNA content, as well as the serum concentrations of corticosterone. Glucocorticoids do not seem to be involved in LPS-induced increase in hypothalamic somatostatin mRNA since adrenalectomy did not prevent this effect. In order to analyze the possible effect of NO, aminoguanidine, an inducible nitric oxide synthase inhibitor, was injected (100 mg/kg s.c.) simultaneously with LPS injection. Aminoguanidine administration did not modify somatostatin mRNA in saline injected rats, but it prevented LPS-induced increase in hypothalamic somatostatin mRNA. These data suggest that the stimulatory effect of endotoxin on hypothalamic somatostatin gene expression is not mediated by glucocorticoids, but instead by the increase in NO release.
 ...
PMID:Endotoxin administration increases hypothalamic somatostatin mRNA through nitric oxide release. 1554 48