Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The familial observations of multiple endocrine neoplasia are rare such that there are only four known cases in France. In our family, two children and their mother are affected. Their mother, at the age of 16, was operated on a medullary thyroid cancer (MTC) and now presents with a phaeochromocytoma. Vanessa also presents with a MTC but without either phaeochromocytoma nor hyperparathyroidism. Her sister was then systematically screened and the only positive test was Pentagastrin. This allowed us to practice a thyroidectomy which will confirm the presence of a medullary thyroid cancer. In all three cases, the Marfan-like features, the abnormal facies and lingual neuromas are all features of the disease. These observations are of interest for the systemic familial screening of MTC by tumour markers (calcitonin, ACE) and by the Pentagastrin test, while awaiting for the use of specific probes on chromosome 10.
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PMID:[A familial case of multiple endocrine neoplasia (MEN IIb). Diagnosis of medullary thyroid cancer]. 257 80

1. The aim of this study was a pharmacological characterization of the multiple NANC inhibitory transmission systems producing relaxation of the circular muscle of guinea-pig proximal colon. In the presence of atropine (1 microM), guanethidine (3 microM) and of the tachykinin NK1 and NK2 receptor antagonists, SR 140333 (0.3 microM) and MEN 10627 (1 microM), respectively, electrical field stimulation (EFS) produced a frequency-dependent (0.1-3 Hz) relaxation. During a cumulative frequency-response curve, the maximal relaxant effect was produced at 3 Hz and approached the maximal relaxation to 1 microM isoprenaline. In the presence of both apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM), EFS failed to evoke relaxation up to 1 Hz; at 1-10 Hz, a slowly developing relaxation ensured which approached 50% of the Emax to isoprenaline. The EFS-evoked NANC relaxation, either in the presence or absence of apamin and L-NOARG, was unaffected by in vitro capsaicin pretreatment (10 microM for 15 min). 2. Three protocols of EFS were developed for further pharmacological analysis: (a) EFS at 1 Hz for 5 s in the presence of L-NOARG, producing a transient fast apamin-sensitive relaxation; (b) EFS at 1 Hz for 5 s in the presence of apamin, producing a transient fast L-NOARG-sensitive relaxation; and (c) EFS at 10 Hz for 5 s in the presence of both apamin and L-NOARG, producing a transient but slowly developing and more sustained relaxation. 3. The neutral endopeptidase inhibitor, thiorphan (1-10 microM), enhanced and prolonged the apamin- and L-NOARG-resistant NANC relaxation produced by EFS at 10 Hz, without affecting that evoked at 1 Hz in the presence of apamin or L-NOARG. The angiotensin converting enzyme inhibitor, captopril (1-10 microM) was without effect. 4. The cAMP analogue inhibitor of protein kinase A, Rp-cAMPs (100-300 microM) significantly reduced and shortened the NANC relaxation produced by 10 Hz EFS in the presence of L-NOARG without affecting that produced by 1 Hz EFS in the presence of apamin or L-NOARG. 5. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid (CPA, 3-10 microM for 60 min) abolished the 1 Hz EFS-induced relaxation in the presence of L-NOARG, and greatly inhibited that produced by 10 Hz EFS in the presence of both apamin and L-NOARG. The relaxation produced by 1 Hz EFS in the presence of apamin was inhibited by about 32% at 10 microM only. 6. Nifedipine (1 microM) did not affect the EFS-induced NANC relaxations. In the presence of nifedipine, tetraethylammonium (TEA, 1 mM) enhanced the 1 Hz EFS-induced relaxation in the presence of L-NOARG (158% of control) and that produced by 10 Hz EFS in the presence of apamin and L-NOARG (215% of control) while that evoked by 1 Hz EFS in the presence of apamin was slightly affected (109% of control). 7. In the presence of atropine, guanethidine, SR 140333 and MEN 10627, bath application of human vasoactive intestinal polypeptide (VIP, 0.1 nM-10 nM) produced a concentration-dependent, slowly developing relaxation of colonic strips. The relaxation to VIP was unaffected by apamin (0.3 microM), L-NOARG (100 microM), nifedipine (1 microM) or nifedipine plus TEA (1 mM); it was inhibited by CPA (10 microM) and Rp-cAMPs (100 microM) and was potentiated by thiorphan (10 microM). 8. The putative VIP receptor antagonist, VIP(10-28) (10 microM) did not affect the VIP-induced relaxation nor the NANC relaxation to 10 Hz EFS in the presence of apamin and L-NOARG. 9. The present findings provide evidence that three distinct NANC inhibitory mechanisms mediate relaxation of the circular muscle of the guinea-pig proximal colon. The first system provides a fast relaxation in response to low frequency of stimulation and may involve the action of a transmitter(s) (possibly ATP) which mobilizes intracellular Ca2+ from sarcoplasmic reticulum leading to the activation of apamin-sensitive K+ channels. The second system likewise provides a fast relaxation of the colon in
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PMID:Characterization of the apamin- and L-nitroarginine-resistant NANC inhibitory transmission to the circular muscle of guinea-pig colon. 888 60

Essential hypertension is one of the most important risk factors for cardiovascular diseases. Its pathophysiological mechanism is unknown. Recent data suggests that deformability and aggregation of red blood cells may play an important role in the regulation of blood rheology in hypertension. Simultaneously there are reports suggesting that antihypertensive effects of angiotensin converting enzyme inhibitors (ACEI) could be counteracted by high doses of aspirin. We postulate that these effects could be related to the changes in blood rheology. Accordingly we designed a study to evaluate the effect of low or high dose of aspirin on deformability and aggregability of red blood cells from patients with essential hypertension. Deformability and aggregability of red blood cells were measured by laser diffractometer (Rheodyn SSD, Myrenne GmbH) and computerized automatic aggregometer (MA1 Myrenne GmbH, Germany), respectively. The effects of aspirin on deformability and aggregation of red blood cells were studied ex vivo in whole blood from three groups of patients with essential hypertension (group I: 10 patients receiving placebo, group II: 23 patients receiving 75 mg/day p.o. aspirin for 3 days, and group III: 23 patients receiving 300 mg/day p.o. aspirin for 3 days). Subjects in all groups received the same combination of antihypertensive agents consisting of: one of ACEI (enalapril or perindopril), one of beta-antagonists (metoprolol or bisoprolol), and diuretic agent (indapamid). In patients receiving high dose of aspirin (300 mg/day) we observed that erythrocyte aggregability was 25% higher than in the placebo group (MEA = 25.8 +/- 6 SD, vs MEA = 20.6 +/- 3 SD, p < 0.05). Aspirin had no effects on deformability of erythrocytes or on arterial blood pressure. High doses of aspirin or possibly also other nonsteroidal anti-inflammatory drugs (NSAID) in patients receiving antihypertensive therapy can directly affect rheological properties of the blood due to the activation of red blood cell aggregation. Increased aggregation of red blood cells during antihypertensive therapy may be an important indicator of the worsening of organ perfusion.
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PMID:[The effect of aspirin on rheological properties of erythrocytes in essential hypertension]. 1215 52

Pheochromocytoma may infrequently lead to dilated cardiomyopathy, which may reverse partially or completely after treatment. Progressive dyspnea, palpitations, and paroxysmal attacks of severe hypertension leading to cardiac failure had developed in a 25-yr-old woman. Chest radiography and echocardiography revealed a massive 4-chamber dilatation of the heart with an ejection fraction of 12%. Twenty-four-h urinary vanillylmandelic acid and metanephrine levels were elevated. Magnetic resonance imaging detected a large mass lesion in the right adrenal gland. Oral glucose tolerance testing revealed diabetes mellitus. Medical drug therapy with alpha-blocker, angiotensin converting enzyme inhibitor, beta-blocker, digoxin, and diuretic rapidly improved her cardiac condition. Repeat echocardiogram showed that the left ventricular function had improved substantially. The clinical condition of excess catecholaminemia (and thus, arterial hypertension and the abnormality of the glucose metabolism) subsided with complete resolution of the congestive heart failure following the surgical removal of the tumor. Evaluation for medullary thyroid carcinoma (MTC) revealed an elevated calcitonin level demonstrated by fine needle aspiration biopsy. There were no biochemical evidences for primary hyperparathyroidism. Multiple endocrine neoplasia 2 (MEN 2A) syndrome was diagnosed. An overwhelming secretion of catecholamine might cause severe cardiomyopathy and impair glucose metabolism, as evidenced by the improvement of both conditions following the medical treatment of catecholaminemia and surgical resection of the tumor.
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PMID:Severe reversible dilated cardiomyopathy in a patient with multiple endocrine neoplasia 2A syndrome. 1669 5