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)

Chronic renal insufficiency (CRI) is associated with growth failure in children and laboratory rats and is considered to be due, in part, to co-existent malnutrition. Alterations in hypothalamic control of growth hormone (GH) secretion have been suggested in uremic patients. We sought to determine whether factors unique to CRI play a role in this disturbance of GH regulation. Using in situ hybridization histochemistry, we compared messenger RNA (mRNA) levels for the hypothalamic neurohormones GH-releasing hormone (GHRH) and somatostatin (SRIH) in three groups: rats with CRI induced by 5/6 nephrectomy (NPX, N = 4); sham-operated, ad libitum fed rats (SAL, N = 5); and sham-operated, pair-fed rats (SPF, N = 5). We also measured plasma GH at 10 minute intervals for a six hour period via intra-atrial cannulae. The NPX group had significantly lower hypothalamic GHRH mRNA concentrations than both other groups; in addition, these levels were significantly lower in the SPF than in the SAL group. Concentrations of hypothalamic SRIH mRNA did not differ significantly among the three experimental groups. Six-hour mean plasma GH concentrations were significantly lower in the SPF (18.3 +/- 1.8 micrograms/liter) than in either the SAL (27.0 +/- 3.3 micrograms/liter) or the NPX groups (36.8 +/- 7.2 micrograms/liter); the difference in the mean plasma GH levels in the NPX vs. the SAL group did not attain statistical significance. This study provides evidence for an effect of CRI on the neuroendocrine control of GH secretion not related to caloric intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in the neuroendocrine control of growth hormone secretion in the uremic rat. 809 33

The chelator somatostatin analogue dota-D-phe(1)-tyr(3)-octreotide (DOTATOC), which is stably labeled with the beta-emitting radioisotope yttrium 90 ((90)Y), is used as internal radiotherapy for the treatment of patients with advanced neuroendocrine tumors. We report 5 patients who developed chronic renal failure, caused in 3 patients by biopsy-proven thrombotic microangiopathy (TMA). Twenty-nine patients (14 men, 15 women) with normal renal function before therapy were treated with divided intravenous doses of (90)Y-DOTATOC approximately 6 weeks apart (mean normalized cumulative dose, 165.4 +/- 36.4 mCi/m(2)). Twenty-two of 29 patients were administered a normalized cumulative dose of 200 mCi/m(2) without side effects. Among the 7 patients (6 women, 1 man) administered a normalized cumulative dose greater than 200 mCi/m(2), 5 patients (4 women, 1 man) developed renal failure. Increasing serum creatinine levels were observed within 3 months after the last (90)Y-DOTATOC injection. The evolution was rapidly progressive in 3 patients, resulting in end-stage renal failure within 6 months. The remaining 2 patients developed chronic renal insufficiency (mean serum creatinine level, 300 micromol/L an average 16 months after the end of treatment). Renal biopsies performed in 3 patients showed typical signs of TMA involving glomeruli, arterioles, and small arteries. Patients treated with high-dose (90)Y-DOTATOC internal radiotherapy (cumulative dose > 200 mCi/m(2)) are at high risk to develop severe renal failure caused by TMA lesions. The histopathologic lesions are identical to those found after external radiotherapy, which suggests a causal relationship between (90)Y-DOTATOC and renal TMA.
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PMID:A new cause of renal thrombotic microangiopathy: yttrium 90-DOTATOC internal radiotherapy. 1127 86

DOTA-D-Phe1-Tyr3-octreotide (DOTATOC), a newly developed somatostatin analogue which can be stably labelled with the beta-emitter yttrium-90, can be used for receptor-mediated internal radiotherapy. A 78-year-old woman suffering from a carcinoid of the small intestine with multiple metastases in the liver as well as mesenteric and supraclavicular lymph node metastases was treated with this therapy after the disease had progressed under other chemotherapy options employed years previously. The patient received four single doses of 90Y-DOTATOC at 6-week intervals, yielding a cumulative dose of 9,620 MBq (5,659 MBq/m2). Restaging revealed stable metastatic disease. Serum creatinine and urea nitrogen levels were within the normal range prior to starting and during DOTATOC therapy. However, 15 months after cessation of DOTATOC therapy, a progressive deterioration of renal function occurred, leading to end-stage renal disease. Urinalysis revealed a slight proteinuria of 700 mg/day without haematuria, leucocyturia or casts. There was no obvious risk factor for chronic renal insufficiency except DOTATOC therapy. However, it was not feasible to use kidney biopsy to prove the presence of radiation-induced nephritis. Intermittent haemodialysis was started as the creatinine clearance declined to below 10 ml/min. Diuresis was not affected. The presented case shows delayed renal insufficiency after a relatively low cumulative dose of 90Y-DOTATOC (5,659 MBq/m2). This serious adverse event indicates that further studies are needed to evaluate which dose of 90Y-DOTATOC, under which renal protection regimen, will provide optimal management, balancing risks and benefits.
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PMID:End-stage renal disease after treatment with 90Y-DOTATOC. 1200 21

The spectrum of polycystic kidney disease (PKD) comprises a family of inherited syndromes defined by renal cyst formation and growth, progressive renal function loss and variable extrarenal manifestations. The most common form, autosomal-dominant PKD is caused by mutations in one of two genes, PKD1 or PKD2. Recent developments in genomic and proteomic medicine have resulted in the discovery of novel genes implicated in the wide variety of less frequent, recessive PKD syndromes. Cysts are the disease, and overall cystic burden, measured by MRI as total kidney volume, is being established as the best available biomarker of disease progression. Current state-of-the-art therapy is aimed at quality treatment for chronic renal insufficiency and cyst-related complications. Recent therapeutic studies have focused on mechanisms reducing intracellular cyclic AMP levels, blocking the renin-angiotensin-aldosterone system and inhibiting the mTOR-signaling pathway. PKD therapies with vasopressin antagonists and somatostatin analogues result in the reduction of intracellular cAMP levels and have shown limited clinical success, but side effects are prominent. Similarly, mTOR pathway inhibition has not shown significant therapeutic benefits. While the HALT-PKD study will answer questions by the end of 2014 about the utility of renin-angiotensin-aldosterone system blockade and aggressive blood pressure control, the next generation of PKD therapy studies targeting proliferative mechanisms of cyst expansion are already under way. Advances in research on the molecular mechanisms of cystogenesis will help design novel targeted PKD therapies in the future.
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PMID:Therapeutic advances in the treatment of polycystic kidney disease. 2557 84