Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Patients with hypertension requiring therapy frequently present with concurrent peripheral vascular disease (PVD). This situation must be taken into account for an optimum antihypertensive treatment. In general, in patients with PVD only a cautious and gradual lowering of the blood pressure is recommended, since the decrease in poststenotic perfusion pressure may accentuate the symptoms of occlusive disease. In intermittent claudication--the most frequent manifestation of occlusive disease beta--receptor blockers today are no longer considered to be contraindicated. In the presence of critical ischemia of the legs (pain at rest and/or necroses) beta blockers should only be given with extreme caution. The agents of choice are calcium antagonists, ACE -inhibitors as well as alpha blockers and some newer vasodilating substances (e.g. Carvedilol). Conventional diuretics show disadvantages. An slightly elevated blood pressure in critical leg ischemia helps to improve the poststenotic perfusion of the affected limb. Antihypertensive treatment should not be instituted in patients whose systolic blood pressure is lower than 160 mmHg.
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PMID:[Antihypertensive therapy in arterial occlusive disease]. 168 38

Pretreatment with captopril, a kininase II inhibitor, at 10 mg/kg i.p. or s.c., significantly increased the writhing response induced by a minimum effective dose (0.75 mg/kg i.p.) of phenylbenzoquinone (PBQ), by 91-148%. 1,10-Phenanthroline, a carboxypeptidase B inhibitor (2 mg/kg i.p.), in combination with captopril enhanced the algesic effect of PBQ by 309-360%. Captopril also doubled the number of writhes induced by a minimum effective dose of BK (5 micrograms/kg i.p.) in PGE2-pretreated mice. The writhing responses induced by higher doses of PBQ or BK were not affected by these inhibitors. The hyperalgesic effect of BK (1 micrograms) injected into the hindpaw of rats was significantly increased and prolonged by coinjection of captopril (30 micrograms) and 1,10-phenanthroline (30 micrograms) and was prevented by carboxypeptidase B (1 mg). These data indicate that BK plays a role in pain in these models, a role which appears of greatest relevance at threshold algesic stimulation.
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PMID:Evidence for a role of bradykinin in experimental pain models. 179 37

Forty-five patients underwent surgical reconstruction with transpedicular fixation of the lumbar spine with narrow AO DCP plates. Preoperatively, all patients underwent spinal imaging with either magnetic resonance imaging, computed tomography, or myelogram as well as provocative discography to determine the location and the number of symptomatic segments. The minimum follow-up in this series was 2 years. The determination of solid posterior fusion in the presence of plate instrumentation was difficult. The patients in the series were classified as having 1) solid fusion; 2) radiographic flaws within the posterolateral fusion without implant failure; or 3) frank pseudarthrosis with implant failure. Thirty-six (80%) of the patients had a solid fusion, 9 of whom required an additional anterior interbody fusion to obtain symptom control. Twenty percent of the patients in the series had radiographic evidence of reabsorption without implant failure. Four patients in the series (8.8%) had screw breakage, three of which required anterior interbody fusions. The highest rate of reabsorption and pseudarthrosis implant failure was in the 12 patients who had three-level instrumentation; 33% of these patients required anterior interbody fusion to obtain a solid arthrodesis. The average preoperative pain scale was 8.9, and the average postoperative pain scale was a 3.3. Twenty-two patients in the series were cigarette smokers and had a slightly lower fusion rate than non-smokers. They did, however, have a higher use of narcotics after surgery. Forty percent of the patients in this series continued to have radiculopathy after their reconstruction. This study demonstrates the utility of transpedicular fixation in salvage lumbar surgery in obtaining a solid arthrodesis with a beneficial clinical result. Anterior interbody fusions are highly successful in the management of pseudarthrosis and implant failure after transpedicular instrumentation.
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PMID:Reconstruction of failed lumbar surgery with narrow AO DCP plates for spinal arthrodesis. 202 35

To assess the anti-anginal and anti-ischaemic efficacy of the ACE-inhibitor enalapril in normotensive coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Eight male patients, aged 45-68 years, with stable effort angina were given enalapril (10 mg) once a day or placebo for 7 days. Maximal exercise stress tests 10w/min in the upright position were performed at the end of each period. In comparison to placebo, enalapril increased significantly 1 mm of ST depression time and decreased significantly ST depression at maximal common work. Moreover, enalapril increased significantly the angina threshold and exercise duration. Three of the eight patients ended the exercise without pain. The rate-pressure product was not significantly modified at any time. Thus, the anti-ischaemic and anti-anginal activity may be due to an increase of coronary blood flow, rather than a reduction of MVO2 consumption.
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PMID:Effects of enalapril in normotensive patients with stable effort angina: a double blind, placebo controlled study. 208 65

Three hundred thirty-one patients with mild to moderate essential hypertension, 182 males and 149 females with a mean age of 54 (range, 17-87 years), were studied for 1 year in a clinical trial with ramipril, an angiotensin converting enzyme (ACE) inhibitor. The patients included had completed double-blind trials with ramipril vs. captopril, HCT, atenolol and ramipril plus piretanide. All cases were treated first with 5 mg ramipril and, where appropriate, also with 25 mg HCT. Adjustment of the dose in the range 1.25-20 mg ramipril was left to the investigator. Overall, a consistent reduction in blood pressure was achieved. Only small changes in mean blood pressure were noted during the 12 months (mean diastolic blood pressure 84.3-86.9 mm Hg, mean systolic blood pressure 145.6-148.2 mm Hg). Two hundred sixty-two (82%) of the 331 patients had diastolic values consistently equal to or lower than 95 mm Hg. There was a downward shift in the dosages upon which the investigators finally settled during the 12-month period in the patients receiving ramipril monotherapy. In patients also receiving HCT the initial dose was increased in most cases. Adverse events were observed in 6.7% of patients taking ramipril alone. The most frequent symptoms were dizziness, asthenia, pain in the upper abdomen and headache. Adverse effects occurred more frequently under continuous additional treatment with HCT, the same symptoms being reported. The clinical trial was prematurely terminated in six patients, in only two cases for medical reasons. The analysis of the laboratory findings revealed no general deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An open multicenter study to assess the long-term efficacy, tolerance, and safety of the oral angiotensin converting enzyme inhibitor ramipril in patients with mild to moderate essential hypertension. 247 9

Augmentation of lumbar spine fusion with internal fixation using pedicle screw systems has gained wide currency because it offers rigid stabilization to foster fusion healing. The AO DCP plate has been employed in Europe as a spinal implant with pedicle fixation using 6.5 mm, full-threaded cancellous bone screws with success. This report details the experience of using this device for lumbar spine fusion in a series of 46 North American patients with a mean follow-up of 1.25 years (range 1-2.5 years). Thirty-one patients had had prior lumbar spine surgery with poor outcomes, and 15 had had no prior surgery. All were treated surgically for lumbar degenerative disease with canal decompression, internal fixation with AO plates, and fusion with autologous bone grafting posterolaterally. Complications included two early and one delayed wound infection; five cases of screw loosening; three cases of screw breakage; and three cases of screw impingement upon a nerve. Results of surgery in 17 patients with failed interbody fusion included good to excellent pain relief in 59%, and solid fusion in 76%. In 14 patients with failed posterior surgery the good to excellent pain relief rate was 79%, and the fusion rate was 86%. In 15 patients undergoing primary surgery there was 89% good to excellent pain relief and a solid fusion rate of 87%. The benefits accruing from augmentation of the fusion with internal fixation using AO DCP plates are positive and justify its continued use. Complications encountered in the early experience have been significantly reduced in subsequent series, indicating the existence of a "learning curve" effect which would mandate specific training of spinal surgeons in the technique.
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PMID:Reconstruction of the lumbar spine using AO DCP plate internal fixation. 291 75

We designed phethiol (1-amino-1-benzyl-2-mercaptoethane) as a potent and selective inhibitor of Zn-containing aminopeptidases. This compound inhibited purified aminopeptidase M (EC.3.4.11.2) with a Ki of 5 nM but was at least 1000 times less potent against other metallopeptidases comprising angiotensin-converting enzyme EC 3.4.15.1), enkephalinase (EC 3.4.24.11), thermolysin (EC 3.4.24.4), or dipeptidylaminopeptidases. Phethiol alone significantly but partially protected endogenous (Met5) enkephalin released from depolarized brain slices, total protection being achieved when it was associated with an enkephalinase inhibitor. In order to obtain a parenterally-active inhibitor of cerebral aminopeptidases, the prodrug carbaphetiol, a readily hydrolyzable S-phenylcarbamoyl derivative of phethiol, was designed. Carbaphethiol (i.v.) elicited a rapid rise in mouse striatal level of Tyr-Gly-Gly, a characteristic extracellular metabolite of enkephalins. Carbapethiol alone and, even more, when associated with an enkephalinase inhibitor, exerted a potent naloxone-reversible antinociceptive activity. Carbaphethiol appears as the first parenterally-active inhibitor of cerebral aminopeptidases, potentially useful in neuropeptides degradation studies and as a pain-suppressing agent.
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PMID:Potent inhibition of cerebral aminopeptidases by carbaphethiol, a parenterally active compound. 324 26

At the present time there is evidence for two families of related peptides which act as ligands for opiate receptor sites. The endorphin group of peptides are derived from the ACTH/LPH precursor pro-opiocortin. The enkephalins appear to be formed from a separate precursor or precursors that have yet to be fully characterized. There appear to be a number of different types of opiate receptors and this may be related to the multiplicity of peptide ligands that have so far been identified. The enkephalins and related peptides appear to have a much wider distribution than the endorphins but the latter may act as circulating hormones unlike the enkephalins. It is likely that both endorphins and enkephalins are involved in sensory modulation processes and release of these peptides has been demonstrated during brain stimulation for pain relief. The enkephalins are very rapidly inactivated by tissue proteases, the aminopeptidases appear largely responsible for the inactivation of exogenously administered enkephalins but the dipeptidyl carboxypeptidase, termed enkephalinase, may have a special inactivating function at enkephalinergic synapses. Evidence will be presented for the biosynthesis, the release and inactivation of the enkephalins relating to the above points.
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PMID:Opioid peptides: aspects of their origin, release and metabolism. 625 71

Hind paw oedema in rats, measured by plethysmography or extravasation of Evans Blue dye into the skin, after subplantar injection of submaximal doses of carrageenin (1-100 micrograms) was significantly increased for 4 h during kininase II inhibition with captopril (1 mg kg-1, s.c.). Submaximal oedema, as assessed by paw swelling, after subplantar bradykinin (0.1-1.0 microgram) was also significantly increased after subcutaneous administration of this dose of captopril, whereas that in response to either histamine (2-20 micrograms) or prostaglandin E2 (2 micrograms) was unchanged. The pain threshold of the paw, injected with carrageenin (1 microgram) was lowered significantly after subcutaneous administration of captopril (1 mg kg-1). Potentiation by captopril (1 mg kg-1, s.c.) of paw swelling in response to intraplantar carrageenin (100 micrograms) or bradykinin (1 microgram) was reduced by prior subcutaneous administration of indomethacin (5 mg kg-1). It is suggested that normally, tissue kininase II activity is sufficient to decrease the inflammatory response of the hind paw to carrageenin or bradykinin. After inhibition of kininase II with captopril, bradykinin levels are increased and interact with concomitantly released prostaglandins to potentiate inflammation.
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PMID:Converting enzyme inhibition in the rat by captopril is accompanied by potentiation of carrageenin-induced inflammation. 632 90

The follow-up of living kidney donors demands medical as well as psychological competence. In the postoperative period, attention focuses on pain management, early detection of wound complications and the prophylaxis of thromboembolism. Regular visits of the donor who may easily feel neglected should be as much part of the transplant team's post-operative routine as visits of the recipient. The later phase of recovery emphasizes strengthening abdominal wall and lumbar muscles as well as the gradual increase of physical activity. Long-term follow-up focuses on the early detection of arterial hypertension and proteinuria. Antihypertensive therapy in nephrectomized donors should include an ACE inhibitor or an angiotensin-II antagonist. In Switzerland, the long-term course after living donation is prospectively monitored by the Swiss Registry for Living Donors founded in 1993. The registry is responsible for the regular timing of follow-up examinations and assures transparency of the origin of the kidneys used for living donation in Switzerland. The registry heavily relies on the collaboration of the donor's family physicians.
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PMID:[Follow-up care of living kidney donors]. 750 64


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