UNIPROT:P61278 - FACTA Search

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

We prospectively evaluated 28 persons with active endocrine ophthalmopathy and positive sonographic criteria (A-mode) on extraocular eye muscles. To evaluate somatostatin-receptor status SPECT of the orbits was performed with a double-headed rotating gamma camera after application of 110 MBq 111-In-Pentreotide. 9 patients (12/56 eyes respectively) showed a marked uptake ratio (> 2 in circular ROIs by semiquantitative calculation) and were selected for lanreotide (30 mg i.m. every 14 d) treatment. 5 individuals had control scan after clinical progression which became positive in two of them. All but one tolerated modest side-effects of lanreotide treatment (diarrhea). Therapy was discontinued after 3-10 months when thyroid eye disease had lead to fibrotic stage. This subgroup, with the exception of two women, who received corticosteroids additionally, presented stable disease. One of those had to be sent to surgery because of endangered optical nerve. Clinical ophthalmological control showed promising results in patients receiving somatostatin analogues at early stage when positive on octreo-scan.
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PMID:[Therapy with somatostatin analogs in patient with orbitopathy and positive Octreoscan]. 1159

Until recently, there was no imaging technique available that could be considered as a reliable measure of inflammation in thyroid-associated opthalmopathy (TAO). Pentetreotide (a synthetic derivative of somatostatin) labeled with 111In has been used to visualize somatostatin receptors in endocrine-related tumours in vivo. It has also been used to measure the orbital uptake in patients with TAO. An increased uptake in the orbit was found in patients with active disease. It was suggested that it is caused by the expression of somatostatin receptors on activated T-lymphocytes. Thus, a positive orbital octreoscan indicates clinically active eye disease in which immunosuppressive treatment might be of therapeutic benefit, in contrast to the fibrotic end stage. Indeed, successful immunosuppression with prednisone, orbital irradiation, or very recently with somatostatin analogues, has been demonstrated in patients with TAO and positive octreoscan. It is inferred that an orbital octreoscan is mainly indicated to select patients with TAO who will benefit from immunosuppression. However, limitations such as cost, nonnegligible radiation burden, nonspecific examination for TAO, and finally, lack of evaluation of eye muscle swelling restrict the widespread use of this technique. It remains to be seen if orbital octreoscan will become a widely available tool in the management of patients with TAO.
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PMID:Octreoscan in thyroid-associated ophthalmopathy. 1195 44

The aim of this prospective, randomized study was to investigate the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye disease (TED) before and 1 and 3 months after treatment with somatostatin analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were studied. Twenty-two patients (13 females) had active eye disease with a clinical activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had a negative one. Fifteen patients from the PA group were selected randomly and received SM-a (PA-S subgroup), while the remaining 7 patients were used as control subgroup (PA-C), received neither therapy, nor placebo. From the 15 patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of SM-a treatment. Ten healthy individuals (6 females) were used as controls (group C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL), sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4, 267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6 +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2 +/- 107.3, respectively) subgroups were also increased compared with PI patients and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/- 123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM-1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8 ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL-1RA were elevated in patients with active TED compared to controls. Furthermore, sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients with active TED.
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PMID:Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues. 1218 98

Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesis in vivo in humans. The current understanding of molecular biology involved in angiogenesis has already led to the identification of a number of potential therapeutic targets, some of them being highly effective angiostatic molecules. Most experimental approaches currently favour or even require the systemic administration of the investigated substances (somatostatin analogues, PKC-inhibitors). However, the systemic administration of bioactive substances always risks significant systemic adverse effects. Due to the morphological characteristics of the eye, local therapies including intraocular injection or even local gene transfer might be feasible. They might provide a valuable opportunity of targeted and sustained delivery of therapeutic proteins to the retina. This review aims to outline the current understanding of the pathogenesis of proliferative diabetic retinopathy and will focus on some as yet experimental, but potentially effective new therapeutic possibilities of this disease.
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PMID:Novel approaches in the treatment of angiogenic eye disease. 1602 67

Graves' Disease (GD) is the most common cause of juvenile thyrotoxicosis in children and adolescents. Regarding its treatment, there are wide differences between individual physicians' regimes and those of physicians in different countries. While Antithyroid Drugs (ATDs) remain the initial treatment of choice in almost all the medical centers in Europe, with surgery used mainly to deal with antithyroid failures, there is increasing interest, especially in US, in the use of radioiodine. Although there are data reporting no significant increase in thyroid neoplasia or gonadal injury in older children and adults receiving outpatient doses of radioiodine, endocrinologists and parents continue to shy away from this therapy, especially in Europe, in young children. Nor is there any increase in congenital abnormalities in the offspring of the adults. Thyroid Eye Disease (TED) is one of the most common manifestations of GD, the pathophysiology of which is not very well understood. However, studies by several investigators have begun to shed light on the many complex factors contributing to the development of ocular symptoms in TED. Thyroid ophthalmopathy in juvenile GD is more common but less severe and more likely to remit completely. Steroids and decompression surgery will very rarely be needed in early childhood. It has to be kept in mind that prolonged prednisone administration, which should be used in some severe cases of TED, is associated with weight gain, immune suppression and growth failure in children. Recent studies have shown successful therapy with the long-acting somatostatin analogues (SM-a), octreotide and lanreotide in adult patients with active TED. The rationale of this therapy is based on recent studies in which somatostatin receptors have been identified within the orbital tissues in TED, both in vitro and in vivo. We recently had the opportunity to treat 3 adolescents with moderately severe TED with SM-a. All had increased clinical activity scores (CAS) and were euthyroid on ATD at the time of initiation of treatment. They received 20 mg octreotide (sandostatin- LAR) i.m. one injection every 30 days for 4 months. Their ophthalmopathies improved substantially and CAS decreased in all the patients. In view of the encouraging therapeutic results in these 3 pediatric patients, SM-a may prove to be a valuable treatment in juvenile ophthalmopathy and a good alternative to corticosteroids. The results using SM-a in the treatment of TED seem promising, but studies with larger numbers of patients are needed before we reach any final conclusions.
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PMID:Ophthalmic complications in juvenile Graves' Disease - clinic and therapeutic approaches. 1644 62

No real new treatment has been developed in the last decade for thyroid eye disease (TED). Glucocorticoids (GC), orbital radiotherapy (OR) or a combination of both, are most frequently used in the treatment of TED for the iv immunosuppressive effects. However, we now have novel information regarding the when and how corticosteroids should be used. In general, the iv route of GC administration is preferable to the oral use. iv GC should be used at much lower doses than previously (4.5 to 6 g cumulative dose), possibly with a small dose of oral prednisone (or equivalent) in the interpulse period and for a few weeks after completion of iv treatment. Careful assessment of patients before treatment for identification of possible risk factors of liver toxicity is mandatory. Finally, monitoring of patients, particularly for liver function, is warranted during and after treatment. Although OR's effectiveness was disputed by a study few years ago, more recent studies have reconfirmed its beneficial role in TED and shown that it still has a positive role to play in patients with active TED. Finally, although Somatostatin-analogs (SM-as) gave the impression some years ago that might represent an effective weapon for TED management and initial, mostly uncontrolled and non-randomized trials with small number of patients supported this notion, newer randomized, double-blind studies with larger number of patients have not confirmed the first optimistic results. The question after that is if SM-as should be considered as a rubber bullet in the treatment of TED and we have to forget about them. The answer should be "no yet," especially in the light that the role of SM-as may be revitalized by the use of analogs with higher affinity for all somatostatin receptors subtypes. Such analogs are now available and under investigation in different diseases with very promising results.
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PMID:Recent developments in the medical treatment of thyroid eye disease. 1675 20

The aim of this study was to investigate the effect of long-term somatostatin analogue (SM-a) treatment on serum levels of free (F) and total (T) insulin-like growth factor (IGF)-I, -II and IGF binding protein (IGFBP) - 1, -2 and -3 in euthyroid patients with active thyroid ophthalmopathy. For this purpose, we measured the above-mentioned parameters in 21 patients (11M, 10F), aged 50.8+/-11.8 years (range 35-70) and 19 healthy individuals matched for age, gender and body mass index (BMI). A total of 4 SM-a (sandostatin LAR((R))-30) injections, each monthly, were administered in each patient and measurements were performed prior to treatment and 20-30 days after the last injection, while in control individuals the same determinations were performed only once. All patients had active thyroid eye disease (TED), with clinical activity scores (CAS) >/= 4 (5.3+/-1.1) and positive orbital octreoscan in both eyes. Serum F and T IGF-I and IGF-II were determined using non-competitive, time-resolved monoclonal immunofluorometric assays. IGFBP-1 and IGFBP-2 were determined by an in-house radioimmunoassay, while IGFBP-3 by commercially available IRMA. Our results showed that F and T IGF-I, -II and IGFBP-1, -2 and -3 levels in patients before and after administration of SM-a were comparable and the levels did not differ significantly from those of controls. Furthermore, no statistically significant differences emerged in the ratio between molar weights of TIGF-I/IGFBP-3 and TIGF-II/IGFBP-3, as well as in the ratio of F/TIGF-I and F/TIGF-II in patients before and after SM-a therapy. Fourteen patients (66%) experienced a decline in CAS of at least >1 point in each eye after SM-a administration, whereas in the remaining the CAS did not change. Finally, no relationship was found between the levels of the above-mentioned parameters (post therapy) and CAS, octreoscan scores and thyroid hormones levels. In conclusion, we showed that although SM-a administration in euthyroid patients with active TED had a beneficial effect in a significant percentage of patients, this effect was not associated with a decline in the circulating IGF-I, -II and IGFBP-1, -2 and -3 levels, at least under the conditions of the present study. It can be postulated that if the mechanism of action of SM-a is through reduction of IGF-I levels, this effect is possibly exerted in the retrobulbar tissues by local paracrine/autocrine action.
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PMID:The effect of long-term somatostatin analogue treatment on free and total insulin-like growth factor (IGF) -I, -II and IGF binding protein -1, -2 and -3 serum levels in euthyroid patients with active thyroid eye disease. 1698 92

Severe Graves' ophthalmopathy constitutes a complex therapeutic challenge and treatment outcome often is not satisfactory. Established methods of treatment include high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Recently, the use of intravenous glucocorticoids has been shown to provide more favorable results than oral glucocorticoids. Novel treatments under investigation include somatostatin analogues, intravenous immunoglobulins and antioxidants. Low-dose immunosuppressive drugs (namely cyclosporine and, possibly, methotrexate) might be useful as an adjunct to established methods, particularly in view of a glucocorticoid-sparing action. Because cytokines play an important role in the pathogenesis of the disease, cytokine antagonists, which are currently evaluated in rheumatoid arthritis and other autoimmune conditions, might constitute in the future a valuable tool for the management of eye disease. Prevention of Graves' ophthalmopathy would be desirable, but so far it is limited to secondary prevention (arrest of progression of subclinical disease to clinical disease) and tertiary prevention (avoidance of deterioration or complications of clinical disease): among preventive measures smoking withdrawal is probably the most important one. Primary prevention (in the absence of disease) is only speculative, but oral tolerance induction or vaccination with the offending antigen(s) might prove beneficial for prevention of Graves' ophthalmopathy in genetically susceptible individuals.
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PMID:Novel approaches to the management of graves' ophthalmopathy. 1711 Mar 59

Children have about the same risk (or slightly increased) as adults to develop Graves' ophthalmopathy (GO) once they have contracted Graves' hyperthyroidism. The severity of childhood GO appears to be less than that of adult GO. The female preponderance is similar between children and adults with Graves' hyperthyroidism (87% and 83%, respectively), but the prevalence of smoking is much lower in children than in adults (4% and 47%, respecttively). Smoking is a risk factor for GO, and the odds increase significantly with increasing severity of GO. It has also been shown that the manifestation of GO begins to resemble the adult findings more closely when adolescence approaches. This could be explained by increasing smoking prevalence with age. A recent study supports the above data and provides a very interesting clue: the difference might be caused by exposure to tobacco smoke. Regarding treatment of thyroid eye disease (TED) in childhood, most physicians who are dealing with such cases prefer a 'wait-and-see' policy. Pharmacological intervention, predominantly with steroids, is considered appropriate in case of worsening of eye changes or no improvement of eye changes when the patient has become euthyroid. Doses between 5 and 20 g prednisone daily are used depending on the severity of the case. It has to be kept in mind that prolonged prednisone administration, which should be used in some severe cases of TED, is associated with weight gain, immune suppression and growth failure in children. Recently, it has been shown that somatostatin analogs (SM-as) might be of therapeutic value in the treatment of active TED in adults. However, initial studies were uncontrolled, non-randomized, and included only small numbers of patients. In the past 2 years, three double-blind, placebo-controlled clinical studies have been published, which have demonstrated only a modest improvement in proptosis. The current range of SM-a drugs target two of five somatostatin receptors present in the orbital tissues of TED patients. Therefore, there is a reason to believe that newer generations of SM-as that target a wider range of somatostatin receptors may show markedly superior results in the treatment of TED. Retrobulbar irradiation, which has proved beneficial in adults with TED, has no place in the treatment of juvenile GO, in view of the theoretical risk of tumor induction. The same applies to orbital decompression.
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PMID:Thyroid-associated ophthalmopathy in juvenile Graves' disease--clinical, endocrine and therapeutic aspects. 1717 81

TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor gamma, interleukin gamma) and Th2 (interleukin -4, -5, -10) profile T cells are activated in the TED. We therefore measured interleukin-gamma, IF-gamma and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (IL-2) and Th2 (IF-gamma) pathways represented by those two cytokines are not involved (IL-10 before 2.29+/-5.23 and after treatment 3.77+/-8.44; IF gamma before 0.50+/-0.24 and after treatment 0.35+/-0.19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25 mm Hertel.
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PMID:No changes in serum concentrations of interleukin 10 (IL-10) and interferon gamma (IF-gamma) before and after treatment of the thyroid eye disease (TED). 1803 96

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