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)

Diabetic neuropathy is common, related to increased morbidity and mortality, and has no effective treatment at present. Interventions based on putative pathways thought to contribute to damage and repair of nerve fibres have yielded little success to date. Pain is a potentially debilitating manifestation of diabetic neuropathy and has many potential sites of origin and, hence, modulation. Its cause is unclear and it does not respond well to traditional pain therapies, proposed to mediate their benefits via multiple peripheral and central mechanisms. A better understanding of the mechanisms leading to nerve fibre degeneration and regeneration as well as pain has recently resulted in the development of a more targeted approach to the treatment of diabetic neuropathy. Thus, specific NMDA receptor antagonists and more specific neuronal serotonin and norepinephrine (noradrenaline) uptake inhibitors offer promise in the treatment of painful diabetic neuropathy. A number of treatments which include the aldose reductase inhibitors and neurotrophins have failed to reach the clinical arena. However, the antioxidant alpha-lipoic acid, as well as compounds which correct vascular dysfunction and hence neuropathy, such as ACE inhibitors and protein kinase C-beta inhibitors, have demonstrated more success.
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PMID:Current and future strategies for the management of diabetic neuropathy. 1598 43

The end-point of this retrospective study was to evaluate the standard of care in terms of in-hospital morbidity and mortality for patients with acute myocardial infarction (AMI) treated by thrombolysis within the first 12 hours from the start of the symptoms in five cardiology centers from Bucarest for a period of 5 years (2000-2004). This retrospective registry on a central database included 1814 patients (73.63% men, mean age 59.9 +/- 11.8 years), presented in an average time of 211.63 minutes from pain start. The most frequently used fibrinolitic was streptokinase (66.21%), administered most often in 30 minutes and for a subgroup in 20 minutes--accelerated regimen, with a good efficiency for the reperfusion of the culprit vessel evaluated non-invasively (clinical, electrical and biological methods). The global in-hospital mortality was 11.1%. The only predictors of in-hospital mortality were female gender and advanced age (>75 years) [p < 0.05]. The rate of haemorrhagic complications was not different from the one described by other clinical studies. The treatment by anticoagulants, antiaplatelets agents like aspirin, ACE inhibitors and statins were significant determinants of in-hospital survival. In the subgroup followed-up for 1 year (315 patients), the most frequent complication was the heart failure. In conclusion, in Bucarest, where availability of primary angioplasty in AMI was limited, thrombolysis with streptokinase was still very much used, with acceptable low in-hospital mortality and relatively high rate of artery reperfusion appreciated by non-invasive methods.
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PMID:[Thrombolysis: Bucarest registry]. 1637 16

Intermittent claudication (IC) is defined by leg muscle pain, cramping and fatigue brought on by ambulation/exercise; relieved on rest; and caused by inadequate blood supply and is the primary symptom of peripheral arterial disease (PAD). PAD has a detrimental effect on the quality of life. PAD is a debilitating atherosclerotic disease of the lower limbs and is associated with an increased risk of cardiovascular morbidity and mortality. IC is an extremely important marker of atheroma. Up to 60% patients with IC have significant underlying coronary and/or carotid disease and 40% of all patients suffering from IC die or suffer a stroke within 5 years of presentation. The therapeutic intervention of IC essentially aims at providing symptomatic relief and reducing the systemic cardiovascular complications. Although exercise therapy is one of the most efficacious conservative treatments for claudication, the pharmacotherapeutic goals can be best achieved through an increase in the walking capacity to improve quality of life and a decrease in rates of amputation. In the development of treatment for IC, an aggressive non-pharmacological intervention and pharmacological treatment of the risk factors associated with IC are considered. In the next 2 years, the results of major trials of drugs that stabilize and regress atherosclerosis such as statins and angiotensin converting enzyme inhibitors, and anti-platelet agents, recombinant growth factors and immune modulators will be available for IC. Levocarnitine (l-carnitine) and a derivative, propionyl levocarnitine, are emerging agents that increase the pain-free walking and improve the quality of life in IC patients by working at the metabolism and exercise performance of ischemic muscles. This article provides a comprehensive review of the pathophysiology involved, diagnosis of IC and existing and emerging pharmacotherapies with rationale for their use in its treatment.
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PMID:Intermittent claudication: an overview. 1638 60

Arterial hypertension must also be consistently treated in patients with PAD. Current guidelines and recommendations have to be considered, although in some patients the walk performance may be affected temporary by blood pressure dropping. In PAD, ideal antihypertensives are ACE inhibitors, AT1 receptor antagonists, calcium channel blockers and also alpha receptor blockers in combination. Beta receptor blockers-indicated in coronary heart disease-do not influence pain-free walking distance (PFWD) in patients with PAD. Diuretics should only be given in low dosage and in combination with other antihypertensive drugs in order to avoid a decrease of blood flow ability with clinical events.
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PMID:[Risk adapted therapy in vascular diseases: antihypertensive treatment in peripheral arterial disease]. 1641 58

Solid pseudopapillary tumours of the pancreas (SPTP) are a distinct clinico-pathological entity that differs from the other cystic pancreatic neoplasms in the young age of onset, the almost exclusive incidence in the female sex and the low degree of malignancy. SPTP is a rare neoplasm that has shown a progressive increase of incidence, passing from 0.17%-2.7% of all exocrine tumours of the pancreas in the 1980's, to 6% in recent reports in 2003. In addition, it accounts for about 5% of cystic neoplasms of the pancreas. With the present paper, in the world literature, updated to August 2005, 887 cases have been described in 248 articles. The histogenesis of these epithelial neoplasms remains uncertain though it is likely that they originate from pluripotent immature pancreatic cells. The tumour is generally of large size and invariably presents a capsule. The diagnosis in most cases is based on compressive symptoms, pain or finding of a palpable mass, while in about 20% of the patients the finding is occasional during abdominal imaging performed for other pathologies. CT and MR are not always sufficient to differentiate with certainty between this type of tumour and other cystic neoplasms of the pancreas such as pseudocysts, parasitic cysts and congenital cysts. Cytological examination in most cases permits the diagnosis of SPTP. The malignancy of these neoplasms is attenuated and local with capsular invasion, lymp-node spread and, only rarely, liver and peritoneal metastases. The surgical treatment has to be radical since the malignancy can only be defined by postoperative histological examination. The treatment consists of three possible options: duodenocephalopancreatectomy, intermediate pancreatectomy, and distal pancreatectomy with or without splenectomy. Intraoperative histological examination is mandatory for the diagnostic confirmation and for the evaluation of negativity of the pancreatic resection margins. Survival after radical resection is excellent. Moreover, in forma metastasizing to the liver an aggressive attitude may be still curative and assure longer survival. The Authors report their experience with three female patients with an average age 18 years (28,19 and 8 years) operated on between 1995 and 2000 for SPTP. Two of the patients were asymptomatic and the finding of the tumour was occasional. The third patient presented jaundice and abdominal pain. The average diameter of the tumours was 6 cm (4, 7 and 7 cm). In all three cases tumour marker values (CEA, Ca19-9, alphaFP) were normal. Only in one case was the preoperative diagnosis correct. The surgical treatment depended on the location of the neoplasms: for the two tumours in the head, in one case an enucleoresection was performed in relation to an exophytic location, while, in the other, a duodenocephalopancreatectomy was performed. In the somatopancreatic tumour a distal splenopancreatectomy was performed. Only in one case (the DCP) the capsule and the surrounding parenchyma were infiltreted by neoplasm. In all cases there was immunohistochemical positivity for alpha1-antitrypsin and for neuron-specific enolase. Neither mortality nor operative morbidity were observed. Follow-up with CT found no relapses in any of the three patients after 5, 7 and 10 years, respectively, after the operation.
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PMID:[Solid pseudopapillary tumor of the pancreas. A report of 3 cases and a review of the literature]. 1673 74

Pain characteristics were examined in 24 patients with myophosphorylase deficiency (McArdle's disease). Pain parameters were related to mutation analyses as well as psychosocial data using a pain questionnaire including an assessment of psychosocial distress and coping measures (Beck Depression Inventory BDI; Kiel Pain Inventory KPI, Multidimensional Fatique Inventory MFI). Twenty-three patients complained of pain, which was intermittent and exercise-induced in 15 patients. Eight patients complained of permanent pain, which was superimposed by exercise-induced pain in 7 patients. Patients reported 3-7 different pain characters and various localisations. Patients with permanent pain were significantly more frequently female, experienced higher impact on general activities and sleep as well as higher scores on the MFI. Furthermore, these patients revealed higher scores regarding several psychosocial risk factors including avoidance behavior whereas patients with intermittent pain predominantly showed endurance coping. There was no correlation between age or disease duration, pain intensity as well as mutation type and development of permanent or intermittent pain. In addition, severity of the clinical phenotype did not correlate with ACE polymorphism. Although McArdle's disease is a muscle glycogenosis with marked biochemical homogeneity, the clinical presentation can be quite heterogeneous. A substantial number of patients revealed permanent pain as a major clinical symptom. As permanent pain is not related to age or disease duration, it might be a clinically important subgroup of McArdle's disease. Gender-related genetic factors as well as maladaptive pain-related coping may contribute to the development of such a chronic pain symptom.
Pain 2006 Oct
PMID:Muscle pain in myophosphorylase deficiency (McArdle's disease): the role of gender, genotype, and pain-related coping. 1679 8

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers antagonists (ARAs) are widely used compounds in various cardiovascular disorders. ACEIs, but not ARAs, inhibit the enzyme dipeptidyl carboxypeptidase which is involved in the conversion of angiotensin I to II and degradation of kinins like bradykinin and substance P. Bradykinin and substance P are potent mediators of inflammation and pain. Hence the study was undertaken to evaluate the effects of captopril (an ACEI) and losartan (an ARA-AT1 receptor antagonist) on thermal and chemical induced nocioception by employing hot plate and acetic acid induced writhing tests respectively in mice. Inbred albino mice weighing between 25-30 g were used and they were divided into two sets, each set containing 7 groups. Control groups received normal saline and the remaining six groups received three doses (0.5, 1 and 2 mg/kg) of captopril and three doses (0.5, 1 and 2 mg/kg) of losartan. Drugs were administered intraperitoneally fifteen minutes before placing the animal over the hot plate or 30 minutes before injecting 0.6% acetic acid. Both drugs dose dependently reduced the reaction time in hot plate method. In chemical induced writhing test, both the drugs reduced the latency of onset of writhing and in captopril pretreated groups, acetic acid induced sustained abdominal contraction without any intermittent relaxation. However, in losartan pretreated animals acetic acid just increased the number of writhings without sustained abdominal contraction. Thus, our study suggests that both drugs have hyperalgesic effects.
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PMID:Effects of captopril and losartan on thermal and chemical induced pain in mice. 1705 37

Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin converting enzyme (ACE) may have roles in trigeminovascular nociceptive mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and their correlation, in a sample of migraineurs. Forty-one patients suffering from migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects (controls) participated in this study. Blood samples were collected from cubital veins. Plasma levels of SP and CGRP were measured by enzyme immunoassay. Plasma ACE activities were measured spectrophotometrically. SP levels in MA (6.6+/-3.7 pg/ml; mean+/-SD) and MO (6.6+/-3.2 pg/ml) were significantly higher than in controls (4.8+/-2.4 pg/ml) (P<0.01). CGRP levels in MA (18.8+/-8.8 pg/ml) and MO (19.1+/-9.4 pg/ml) were also significantly higher than in controls (13.4+/-4.4 pg/ml) (P<0.01). ACE activities in MA (34.6+/-19.0 U/l) were significantly higher than in MO (25.3+/-13.2 U/l) and controls (27.0+/-20.4 U/l) (P<0.05). There was a significant correlation between SP and CGRP levels (P<0.05). In MA, SP and CGRP showed a tendency toward positive correlation, which was not significant. There was a weak, but significant positive correlation between SP levels and ACE activities (P<0.01). However, a relationship between ACE activities and CGRP levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to migraine pathophysiology, and that they may interact.
Pain 2007 Apr
PMID:Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods. 1712 35

Diabetic painful neuropathy (DPN) is one of the most common causes of neuropathic pain. The management of DPN consists of excluding other causes of painful peripheral neuropathy, maximising diabetic control and using medications to alleviate pain. The precise relationship between glycaemic control and the development and severity of DPN remains controversial. In this context, drugs such as aldose reductase inhibitors, ACE inhibitors, lipid-lowering agents and alpha-lipoic acid (thioctic acid) may have a useful role to play. There is also evidence that a successful pancreatic transplant may improve symptoms over time, but the mainstay of management continues to be symptomatic control of pain with drugs. Evidence from placebo-controlled studies has shown that opioids, antiepileptic and antidepressant drugs together with capsaicin are effective for alleviating DPN. Tramadol and oxycodone have been shown to be effective in studies of limited duration but their adverse effects, such as constipation and physical dependency, may limit their usefulness as a first-line treatment for DPN. Of the antidepressant drugs, the tricyclic antidepressants have been shown to be effective for alleviating DPN. These medications are widely used but their anticholinergic and sedative properties may not be well tolerated by patients. There is also good evidence that the serotonin-noradrenaline reuptake inhibitor antidepressant drugs venlafaxine and duloxetine are effective for treating DPN. However, venlafaxine may cause cardiac dysrhythmias, and patients using this medication require careful cardiac monitoring. Duloxetine appears to be less cardiotoxic and is licensed in the US and EU for alleviating DPN. The gabapentinoid group of drugs, gabapentin and pregabalin, appear to be the most evidence-based of the antiepileptic drugs for treating DPN. Large placebo-controlled studies have been performed with both of these agents. For many patients, it is still unclear what advantages pregabalin has over gabapentin for DPN. Until better evidence emerges, the potential availability of less expensive generic formulations of gabapentin, together with greater experience with its use, favour gabapentin as the main antiepileptic drug for alleviating DPN. Topiramate, lamotrigine, sodium valproate and oxcarbazepine have been shown to be effective in smaller studies but do not have the same evidence base as the gabapentinoid group of drugs. Of the newer antiepileptic drugs, lacosamide appears to be the most promising for alleviating DPN. Capsaicin has the best evidence base of all the topical agents, but local anaesthetic patches may also have a useful therapeutic role. It is not possible to nominate a single drug as the first-line treatment for DPN and there is evidence that a low-dose combination of two or more drugs rather than a single agent may provide better symptomatic relief with fewer adverse effects. Further studies are necessary to clarify the best combination(s) of treatment for DPN.
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PMID:Diabetic painful neuropathy: current and future treatment options. 1735 15

A 48-year-old African-American woman with both sickle cell anemia and chronic pain was treated with a hydrophobic angiotensin I-converting enzyme (ACE) inhibitor. This resulted in the complete resolution of her pain. When the ACE inhibitor was deliberately stopped, her pain recurred, only to cease again after the ACE inhibitor was deliberately resumed. The activation of ACE may be an early step in the arterial vaso-occlusion typical of sickle cell disease.
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PMID:The prevention of pain from sickle cell disease by trandolapril. 1739 52


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