Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Drug
Enzyme
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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
ACE
-inhibitor lisinopril has previously been shown to be effective in migraine prophylaxis at a daily dose of 20 mg. To test the effect of a low dose of lisinopril (5 mg daily) in migraine prevention, we performed an open label study in 21 migraineurs. The primary outcome measure was frequency of migraine attacks. Secondary efficacy measures were migraine hours, intake of acute migraine drugs,
pain
intensity and responder rate. Compared with baseline conditions, the attack frequency of migraine attacks was significantly reduced (P < 0.0005). The number of acute migraine drugs dropped significantly (P = 0.002). Three patients dropped out because of intolerable cough. Our study suggests that even low doses of lisinopril may be effective in migraine treatment. However, its use may be limited by intolerable side-effects.
...
PMID:Efficacy of lisinopril in migraine prophylaxis--an open label study. 1759 24
Peripheral arterial disease (PAD) of the lower limbs is the third most important site of atherosclerotic disease alongside coronary heart disease (CHD) and cerebrovascular disease (CVD). Best medical treatment is beneficial even in patients who eventually need invasive treatment, as the safety, immediate success, and durability of intervention is greatly improved in patients who adhere to best medical treatment. In recent years, a number of studies have suggested that the
ACE
-inhibitor ramipril and different statins, together with antiplatelet drugs, reduce cardiovascular morbidity and mortality in PAD. Patients with PAD are really a category of patients with a very high cardiovascular risk burden for fatal and nonfatal cerebrovascular and cardiovascular events; therefore, they need to be treated not only for local problems deriving from arteriopathy (intermittent claudication, rest
pain
and/or ulcers) but, above all, for preventing vascular events. Statins not only lower the risk of vascular events, but they also improve the symptoms associated with PAD. Statins exert beneficial pleiotropic effects on hemostasis, vasculature and inflammatory markers; there is also evidence that statins improve renal function considering that the plasma creatinine level is considered as an emerging vascular risk factor.
...
PMID:Statins and peripheral arterial disease: effects on claudication, disease progression, and prevention of cardiovascular events. 1756 Apr 52
In systemic sclerosis (SSc) occurrence of recurrent digital ulcers (DU) is cause of
pain
and functional disability of hands. Treatment with vasodilator agents, such as calcium channel blockers,
ACE
inhibitors, prostanoids, has not shown to be an effective therapy. There is evidence that endotelin-1 (ET-1) is a key mediator in regulation of vascular tone and its enhanced production in SSc is believed to lead to vasoconstriction, vessel remodelling, local ischemia and ulcers of fingertips. Recently, an oral endothelin receptor antagonist, bosentan, has been proved to be effective in the treatment of SSc associated pulmonar arterial hypertension (PAH) and to decrease the development of new DU in patients with SSc. In this study, we assessed the occurrence of new DU in eight patients with SSc associated PAH and one SSc patient with recurrent DU refractory to standard vasodilatation therapy. All patients received bosentan at dosage of 62.5 mg bid for 4 weeks and 125 mg bid thereafter for one year. All patients had 3-4 DU of hands at baseline and one patients had also ulcers at lower limbs. In seven out of nine patients we did not record the occurrence of new DU and we also observed a 50% reduction of existing DU, whereas new DU occurred only in two patients. These data suggest that ET-1 plays a key role in DU induction in SSc patients and that ET-1 inhibition by bosentan can be an effective therapeutic strategy.
...
PMID:[Treatment of digital ulcers in systemtic sclerosis with endothelin-1 receptor antagonist (bosentan)]. 1760 93
Non-steroidal anti-inflammatory drugs (NSAIDs) such as piroxicam and mefenamic acid are commonly prescribed to treat inflammation,
pain
and fever. Similarly acetylsalicylic acid is used to prevent strokes and heart attacks. A rapid and selective method was developed for the simultaneous assay of three NSAIDs and salicylic acid via HPLC with fluorescence detection. The separation was performed using a "dual-mode" gradient (acetonitrile-0.1% aqueous orthophosphoric acid) and the analysis was completed within 7 min using an
ACE
column C18, 5 microm, 150 mm x 4.6 mm. Naproxen was used as internal standard. The proposed method is simple, selective as well as with a good sensitivity reaching LOD lower than 2 pmol (0.05 microM) and was applied for quantitative analysis in pharmaceuticals and in human serum samples. The mean recovery was more than 95% and the within-day and between-days precisions were found to be satisfactory having RSD within the acceptable limits (<10%).
...
PMID:Determination of non-steroidal anti-inflammatory drugs in pharmaceuticals and human serum by dual-mode gradient HPLC and fluorescence detection. 1764 36
The aim of this study was to analyse how plasma glucose level and diabetes mellitus (DM) are associated with chronic pain in the adult population. A structured interview and health examination study with 480 participants aged 30-65 years was carried out in Lapinlahti municipality in Eastern Finland. Chronic pain (duration of at least 3 months) was graded according to frequency: being present less often than daily, or every day or continuously (daily chronic pain,
DCP
). Elevated plasma glucose was defined as a plasma glucose level 6.1 mmol/l. DM diagnosis was based on self-reported diagnoses, reimbursed medication or a health examination with laboratory tests. Glucose regulation status was defined according to fasting plasma glucose level and a two-hour glucose tolerance test. Of the total sample, 90 subjects (19%) had a plasma glucose level > or = 6.1 mmol/l and 55 subjects (11%) had diabetes. The prevalence of daily chronic pain was 21% (N = 101) in all the subjects. In the subjects with a normal plasma glucose level, the prevalence was 18%, while in those with an elevated plasma glucose level it was 38%. The corresponding percentages for non-diabetics and diabetics were 19% and 42%. In the multinomial multivariate logistic regression analysis, glucose level or diabetes was associated with
DCP
. The odds for
DCP
in the subjects with an elevated plasma glucose level was 2.37 (95% CI, 1.26-4.49), and in those with DM it was 2.53 (95% CI, 1.12-5.72). Elevated plasma glucose level and DM are associated with
DCP
in adults.
Pain
2008 Jul
PMID:Chronic pain, impaired glucose tolerance and diabetes: a community-based study. 1786 22
Different components of the renin-angiotensin system (RAS) have been demonstrated in atherosclerotic plaques. However, the involvement of the RAS in the complex process of in-stent restenosis is not yet clear. In this prospective, randomized, double-blind, controlled proof-of-concept study, we compared the 2 different pharmacological approaches, selective AT(1)-receptor-blockade with candesartan vs
ACE
inhibition with quinapril to reduce in-stent restenosis after stent angioplasty of the superficial femoral artery. Twenty-two hypertensive patients with stage IIb peripheral occlusive arterial disease and severe claudication who had been successfully treated with percutaneous transluminal angioplasty (PTA) and stent implantation were randomly assigned to receive daily doses of either candesartan (32 mg) or quinapril (20 mg). Primary end point was restenosis 6 months after intervention, assessed by angiography. Secondary end points were
pain
-free walking distance, determined by treadmill ergometry; determination of crurobrachial indices; and intima-media thickness (IMT). At 6 months, the rate of restenosis on angiography was 34% in the candesartan group and 71% in the quinapril group (P = .043). Relevant restenosis was found in 3 patients (27%) in the candesartan group and in 7 patients (64%) in the quinapril group. Patients in the candesartan group were able to walk farther on a treadmill (increase: 135 m +/- 20 m) compared with patients in the quinapril group (increase: 83 m +/- 21 m). The IMT at the stent edge was not significantly different in the 2 groups (candesartan: 1.9 mm +/- 0.5 mm; quinapril: 2.0 mm +/- 0.3 mm). This study revealed significant benefit of a pharmacological restenosis regimen using the AT(1)-receptor antagonist candesartan in patients with severe atherosclerosis after superficial femoral artery stenting compared with treatment with the
ACE
inhibitor quinapril. Further prospective studies in patients are required to confirm these results.
...
PMID:Comparison of selective AT1-receptor blockade versus ACE inhibition for restenosis prophylaxis in patients with peripheral occlusive arterial disease after stent angioplasty: a randomized, controlled, proof-of-concept study. 1792 25
The leading cause of acute myocardial infarction (AMI) in patients with coronary heart disease is plaque rupture. Between 6% and 12% of AMI patients have angiographically normal coronary arteries. However, new procedures have demonstrated the limits of coronarography and challenged the existence of this situation. Angiograms may fail to detect minimal lesions whereas, in many cases, intravascular sonography reveals small atherosclerotic plaques. With the development of intravascular sonography and multislice computed tomography, the prevalence of myocardial infarction with normal coronary arteries has fallen to about 1%. Myocardial infarction with normal coronary arteries may be due to coronary vasospasm, hypercoagulable states, intense sympathetic stimulation, non atherosclerotic coronary disease, alcohol or cocaine abuse, and systemic diseases. In a series of 1205 AMI patients, we found no significant coronary disease in 45 patients, but intravascular sonography showed minimal intracoronary plaque in 21 of these cases. The 24 patients without significant lesions were young, had no risk factors for AMI without a prodrome, low peak creatine release, a small reduction in the left ventricular ejection fraction after thrombolysis or angioplasty, and good outcome at 26 months. The mechanisms of AMI in these 24 patients were coronary spasm, myocardial bridge, a prothrombotic state, contraceptive pill usage, and drug or alcohol abuse. The diferential diagnoses of these cases of AMI are acute myocarditis and stress cardiomyopathy, and apical left ventricular ballooning. Initial management is the same as for "conventional" AMI, including
pain
relief nitrates, antiplatelet agents, heparin, thrombolysis or angioplasty in the acute phase, and
ACE
inhibitors. Patients with spasm should receive calcium antagonists rather than beta-blockers. The prognosis of these patients is better than that of patients with atherosclerotic lesions. They nonetheless need close follow-up and strict secondary prevention measures, including smoking cessation and prevention of dyslipidemia and diabetes.
...
PMID:[Myocardial infarction with "angiographycally normal coronary arteries" myth or reality?]. 1822 36
Aim of the investigation was the study of influence of spironolactone (25 - 75 mg/day) on clinico-functional status, parameters of left ventricular (LV) remodeling, as well as safety of its long term application in patients with chronic heart failure (CHF) receiving optimal therapy. Forty nine patients were included in the study - 44 men (89,8%) and 5 women (10,2%) in the age from 28 to 75 years with II-IV NYHA functional class (FC) CHF, LV ejection fraction (EF) 35%, plasma levels of creatinine 150 mmol/L and potassium 5 mmol/L. Main causes of development of CHF were dilated cardiomyopathy, ischemic heart disease (large focal postinfarction cardiosclerosis) and decompensated hypertensive heart [25/20/4 (51%/40,8%/8,2%), respectively]. As a result of randomization procedure 2 groups of observation were formed: group 1 - 19 patients receiving spironolactone in a 24 hour dose 25 - 75 mg, group 2 - control group - 30 patients without therapy with spironolactone. Inhibitors of
angiotensin converting enzyme
(
ACE
) took 100%, b-adrenoblockers - 63,2% of patients. Control examination was conducted before randomization, in 6 and 12 months of follow up. During period of observation no changes of FC were noted in control group. In the group of treatment with spironolactone after 6 months in 6 patients FC lowered ( =0,028). By the end of follow up the given effect lost its significance, but 5 (38,5%) patients by termination of the study had FC II of CHF, what was accompanied with moderate increase of distance walked during 6-minute walk test from 354 to 378 m. In patients in the group of spironolactone treatment already after 6 months of treatment there occurred decrease of LV volumes, what by the end of period of observation for LV end diastolic volume (EDV) amounted - 76 ( - 118; - 7), and for LV end systolic volume (ESV) - 53 ml ( - 96; - 7) ml ( =0,008) at absolute increment of LVEF by 3 (0; 12)% ( =0,05). In control group in 12 months decrease of LVEDV was less pronounced and LV ESV did not change. Finally after 12 months of observation the groups became to differ by change of LVEF ( =0,035) and LVESV ( =0,02). Changes of LV volumes were followed by lowering of median concentration of atrial natriuretic peptide (ANP) in plasma by - 51,9 ( - 87; - 43,9) mg/ml. At the same time in control group gradual rise of concentration of the given peptide was observed from initial 107,3 to 168,5 mg/ml at the moment of study termination. Changes of BP level, creatinine concentration in patients in the study were not fixed in any of treatment groups. Development of moderate hyperkaliemia amounted 21.0%, gynecomastia or
pain
in the region of mammary glands were fixed in 26,3% of patients in 12 months of treatment. Addition of spironolactone in a dose of 75 mg/day to optimal therapy, including
ACE
inhibitor and b-adrenoblocker is accompanied with improvement of clinical state and FC of patients with moderate and severe CHF. Long term therapy with spironolactone blocks processes of desadaptive LV remodeling and improves LV contractile function, what is reflected in lowering of ANP concentration in plasma of patients with CHF. Application of spironolactone in combination with
ACE
inhibitor and b-adrenoblocker bisoprolol does not lead to lowering of BP level and worsening of renal function, but is accompanied with development of hyperkaliemia in patients with CHF. Gynecomastia appears to be main reason limiting long term use of spironolactone in patients with CHF in a dose of 75 mg/day.
...
PMID:[Efficacy and safety of long-term application of spironolactone in patients with moderate and severe chronic heart failure receiving optimal therapy]. 1826 Sep 39
Many painful conditions occur more frequently in women, and estrogen is a predisposing factor. Estrogen may contribute to some
pain
syndromes by enhancing axon outgrowth by sensory dorsal root ganglion (DRG) neurons. The objective of the present study was to define mechanisms by which estrogen elicits axon sprouting. The estrogen receptor-alpha agonist propyl pyrazole triol induced neurite outgrowth from cultured neonatal DRG neurons, whereas the estrogen receptor-beta agonist diarylpropionitrile was ineffective. 17beta-Estradiol (E2) elicited sprouting from peripherin-positive unmyelinated neurons, but not larger NF200-positive myelinated neurons. Microarray analysis showed that E2 up-regulates angiotensin II (ANGII) receptor type 2 (AT2) mRNA in vitro, and studies in adult rats confirmed increased DRG mRNA and protein in vivo. AT2 plays a central role in E2-induced axon sprouting because AT2 blockade by PD123,319 eliminated estrogen-mediated sprouting in vitro. We assessed whether AT2 may be responding to locally synthesized ANGII. DRG from adult rats expressed mRNA for renin, angiotensinogen, and
angiotensin converting enzyme
(
ACE
), and protein products were present and occasionally colocalized within neurons and other DRG cells. We determined if locally synthesized ANGII plays a role in estrogen-mediated sprouting by blocking its formation using the
ACE
inhibitor enalapril.
ACE
inhibition prevented estrogen-induced neuritogenesis. These findings support the hypothesis that estrogen promotes DRG nociceptor axon sprouting by up-regulating the AT2 receptor, and that locally synthesized ANGII can induce axon formation. Therefore, estrogen may contribute to some
pain
syndromes by enhancing the pro-neuritogenic effects of AT2 activation by ANGII.
...
PMID:Estrogen elicits dorsal root ganglion axon sprouting via a renin-angiotensin system. 1838 95
Peripheral arterial disease (PAD), usually caused by atherosclerosis, is defined as an obstructive arterial disease of the lower extremities that reduces arterial flow during exercise or, in advanced stages, at rest. It affects more than 8.5 million people in the USA. PAD may appear as an asymptomatic arterial disease with abnormal noninvasive test results, or as a symptomatic disease presenting with atypical limb pain, classic intermittent claudication, or critical limb ischemia. The spectrum of PAD is not a continuum. Patients who present with critical limb ischemia may have experienced minimum symptoms. PAD results in limitation of exercise and walking ability, described as intermittent claudication. Patients with PAD are physically impaired and have a higher risk of cardiovascular events; therefore, the treatment goals are aimed at decreasing their cardiovascular risk, as well as improving exercise and daily functional performance. Apart from supervised exercise, which is a major treatment modality for patients with PAD, as of yet there have been very few significant pharmacological breakthroughs in the treatment of PAD that increases blood flow to the ischemic limb. Although percutaneous intervention has markedly improved the treatment of PAD, bypass surgery continues to play an important role. For the most part medical therapy for PAD is designed as a secondary prevention for cardiovascular risk. These include antiplatelet therapy, statins,
ACE
-inhibitors, smoking cessation and possibly antihypertensive therapy. Revascularization is most beneficial for patients with lifestyle limiting symptoms, acute or chronic limb ischemia with resting
pain
or nonhealing ulcers. In the following review article we will try to explore the clinical role of some of the latest developments in this field.
...
PMID:Peripheral artery disease: therapeutic advances. 1840 43
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