Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.
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PMID:Abnormalities of peptide metabolism in Alzheimer disease. 1618 Oct 81

Splanchnic arterial relaxation is the most important pathology in systemic circulation of portal hypertensive patients. Progressive decline of splanchnic vascular resistance is responsible for development of circulatory dysfunction syndrome (CDS), associated with reduction of effective blood volume within central vascular compartment and compensatory stimulation of vasopressor and natrium retaining hormonal mechanisms. Advanced CDS is characterized by increased cardiac output, tachycardia and low arterial pressure. Complications of CDS have functional nature and comprise: renal failure (hepatorenal syndrome), respiratory failure in context of hepatopulmonary syndrome, cardiac insufficiency produced by portopulmonary hypertension or portal cardiomyopathy, hemorrhages from digestive tract caused by hypertensive portal gastropathy or derangements of brain perfusion. The management of CDS relies on adequate filling of vascular system (albumin), constriction of arterial splanchnic vessels (beta-blocker, analogs of vasopressin and somatostatin), reduction of cardiac output (beta-blocker) and giving support to local vasoprotective mechanisms (prostaglandins, nitric oxide, blockade of ET-A receptors).
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PMID:[Circulatory dysfunction syndrome associated with liver cirrhosis]. 1619 May 66

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).
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PMID:[A case of GH and TSH secreting pituitary macroadenoma]. 1696 20

Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.
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PMID:Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs. 1704 90

The prevalence of malignant pheochromocytoma is about 10%, and is somewhat higher for paraganglioma. A problem for clinical follow-up is that patients with "benign" histopathologic findings may develop metastatic disease. At the first international symposium on pheochromocytoma in Bethesda (2005) experts from different disciplines and patients shared their experiences, and the present knowledge of this rare disease was updated. The discussion related to future strategies for better clinical/histopathologic diagnosis and understanding of different geno- and phenotypes. Curative surgery can only seldom be performed because of multiple metastases. The main therapeutic goal is therefore often tumor reduction and control of hypertension. To date the best adjunct to surgery is radionuclide therapy using 131I-MIBG, but the background information for optimal treatment is still incomplete. Certain patients may benefit from 131I-MIBG combined with radiotherapy via somatostatin receptors expressed by the tumor, or the combination with chemotherapy. The need for future multicenter studies was emphasized. In experimental models the work on enhanced expression of amine transporters critical for radiotherapy is continued. Ongoing microarray studies will reveal novel intracellular pathways of importance for proliferation/cell cycle control, which can be inhibited by pharmacologic tools.
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PMID:Malignant pheochromocytoma: state of the field with future projections. 1710 14

The C57BL/6J mice are inbred strains and develop the metabolic syndrome of obesity, hyperinsulinemia, hyperglycemia, and hypertension, when fed a high-fat diet. These features are similar to those observed in the human metabolic syndrome. This article examined the effect of fat-enriched (FE) diet on the pattern of distribution of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP)-positive cells in the pancreatic islets of C57BL/6J mice using immunohistochemical methods. Insulin-immunoreactive cells were observed in both the peripheral and central regions of the islets of Langerhans in both FE- and control diet-fed mice. The percentage distribution of insulin-positive cells was similar in FE (83.5 +/- 6.4) compared to control diet-fed C57BL/6J mice (83.8 +/- 6.5). Glucagon-containing cells were discerned in the periphery of pancreatic islets in both FE- and control diet-fed mice. The percentage distribution of glucagon was not statistically different in mice fed with FE (9.9 +/- 2.7) compared to control diet (11.3 +/- 4.9). Somatostatin-positive cells were seen in the outer part of the islet of Langerhans and constitute 12.1% (+/-6.3) and 10% (+/-5.5) of pancreatic islet cells in FE- and control diet-fed mice, respectively. PP-immunoreactive cells were observed in the peripheral region of the pancreatic islets of both FE- and control diet-fed mice. The percentage distribution of PP-positive cells was significantly (2.0 +/- 1.2) lower compared to control (5.1 +/- 2.4). In conclusion, the number of PP is significantly reduced in FE diet-fed mice and may play a role in the pathogenesis of diet-induced metabolic syndrome in C57BL/6J mice.
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PMID:The effect of a fat-enriched diet on the pattern of distribution of pancreatic islet cells in the C57BL/6J mice. 1715 15

Raised plasma levels of insulin, glucose and glucagon are found in patients affected by 'hyperinsulinism'. Obesity, hypertension, mammary plus ovary cysts and rheumatic symptoms are frequently observed in these patients. Sleep disorders and depression are also present in most subjects affected by this polysymptomatic disorder. The simultaneous increases of glucose, insulin and glucagon plasma levels seen in these patients indicate that the normal crosstalk between A cells, B cells and D cells is disrupted. With respect to this, it is well known that glucose excites B cells (which secrete insulin) and inhibits A cells (which secrete glucagon), which in turn excites D cells (which secrete somatostatin). Gastrointestinal hormones (incretins) modulate this crosstalk both directly and indirectly throughout pancreatic and hepatobiliary mechanisms. The above factors depend on autonomic nervous system mediation. For instance, acetylcholine released from parasympathetic nerves excites both B and A cells. Noradrenaline released from sympathetic nerves and adrenaline secreted from the adrenal glands inhibit B cells and excite A cells, which are crowded with beta(2)- and alpha(2)-receptors, respectively. Noradrenaline released from sympathetic nerves also excites A cells by acting at alpha(1)-receptors located at this level. According to this, the excessive release of noradrenaline from these nerves should provoke an enhancement of glucagon secretion which will result in overexcitation of insulin secretion from B cells. That is the disorder seen in the so-called 'hyperinsulinism', in which raised plasma levels of glucose, insulin and glucagon coexist. Taking into account that neural sympathetic activity is positively correlated to the A5 noradrenergic nucleus and median raphe serotonergic neurons, and negatively correlated to the A6 noradrenergic, the dorsal raphe serotonergic and the C1 adrenergic neurons, we postulate that this unbalanced central nervous system circuitry is responsible for the hyperinsulinism syndrome.
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PMID:Central nervous system circuitry involved in the hyperinsulinism syndrome. 1716 39

The diabetes epidemic continues unabated, leading to an increasing number of acute and chronic complications, including sight-threatening proliferative diabetic retinopathy. Currently, there is no accepted pharmaceutical therapy for diabetic retinopathy besides nearnormal glycemia, treatment of hypertension, and dyslipidemia. For an effective treatment of retinopathy, one would recommend a concept leading to the downregulation of endogenous angiogenic stimulators and the upregulation of endogenous angiogenic inhibitors, resulting in a restoration of the balance in angiogenic control. The naturally occurring growth hormone inhibitor, somatostatin, has been suggested as candidate for developing novel therapies. Somatostatin may exert its antiangiogenic effects, both through antagonism of the growth hormone axis and through direct antiproliferative and apoptotic effects on endothelial cells. Therefore, the use of long-acting somatostatin analogues will lead to an upregulation of antiangiogenic signaling. Use of long-acting somatostatin analogues in diabetic retinopathy would be an important extension of the initial concept that somatostatin is a regulator of growth hormone secretion only. Currently available analogues have already allowed to modulate the expression of diabetic retinopathy at various disease stages. Somatostatin analogues remain the only nondestructive therapeutic alternative to patients with proliferative diabetic retinopathy who have failed to respond to panretinal photocoagulation.
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PMID:Use of long-acting somatostatin analogue treatment in diabetic retinopathy. 1724 82

Low-grade non-Hodgkin lymphomas (NHLs) at advanced stage are still incurable, and treatment may include chemotherapy with a single drug or a combination of different drugs. With a combination of cyclophosphamide, somatostatin, bromocriptin, retinoids, melatonin, and adrenocorticotropic hormone, we already reported 100% of global response (50% complete response and 50% partial response) in 12 patients with low-grade NHL at advanced stage: 4 previously untreated patients and 8 with relapse of disease after single or combined chemotherapy and therapy free time >or=6 months. This provided the rationale to treat a patient affected by low-grade NHL stage 4, with cyclophosphamide, somatostatin, bromocriptin, retinoids, and melatonin (adrenocorticotropic hormone was not administered for high blood pressure). The patient was treated for at least 2 months. After this period, if he had stable or responding disease, he received an additional 3 months of treatment, and if he was stable or responding after 5 months he was treated for 3 months and more. After 2 months the patient had a partial response, and after 5 months he achieved a complete response. Today, 18 months after the beginning of treatment, the patient is in complete remission. Treatment had very good tolerance, and the patient carried on at home doing his normal activities.
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PMID:Low-grade non-Hodgkin lymphoma at advanced stage: a case successfully treated with cyclophosphamide plus somatostatin, bromocriptine, retinoids, and melatonin. 1730 79


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