Angiotensin Converting Enzyme Inhibitor Drugs Research Articles

339 Angiotensin Converting Enzyme Inhibitor Drug Use and Risk of Finding Pre-Cancerous Colonic Polyps on Initial Colonoscopies

INTRODUCTION: The widespread use of Angiotensin converting enzyme inhibitors (ACEi), especially lisinopril, and their association with colorectal cancer (CRC) has been studied with mixed results. Data suggest angiotensin II inhibition may decrease CRC risk. Contrasting studies suggest a role for kinins in pro-angiogenic effects with their accumulation blunting the effects of angiotensin II inhibition. Since ACEi’s affect both angiotensin II and bradykinin levels, we studied the effect of lisinopril on the risk of developing pre-cancerous (PC) colon polyps. METHODS: Data were collected on 3,541 patients admitted to the Louisville Veterans Affairs Medical Center, and 2,312 were excluded based on specific criteria, including pro-inflammatory states postulated to increase polyposis (e.g., IBD history and pre-existing malignancies). Of the 1,229 patients who were included, 393 (32%) used lisinopril; median age was 61; 88% of patients were male; and 24% were African American. Retrospective chart review of the patients’ active medications at the time of initial colonoscopy was done. Lisinopril use was further stratified by duration of usage. A Poisson Regression Model was employed for analysis with upper and lower bounds, and rate ratios (RR) with corresponding P-values calculated. Statistical significance was set at P < 0.05. Age, sex, race, smoking history, and NSAID use were controlled for. RESULTS: Our study indicates that long-term lisinopril use may be associated with increased PC colon polyp rates. Long-term (>10 years) lisinopril use was associated with a 35% increase in PC colon polyp risk (n = 46, RR = 1.35, P = 0.049). Short-term (<5 years) lisinopril use was associated with a 4%, statistically insignificant, increase in PC polyp risk (n = 273, RR = 1.04, P = 0.64). The total exposure (defined here as dose multiplied by years of use) of lisinopril did not show any difference in risk. CONCLUSION: The mechanisms of ACEi effects are complex and relate to their specific pharmacological properties. It needs to be determined whether or not the accumulation of kinins generated by ACEi’s attenuates their overall anti-angiogenesis effect. Our study indicates that long-term use of lisinopril, irrespective of dose, may increase PC colon polyp risk. This suggests that long-term usage changes the dynamics of the pro- and anti-neoplastic effects of ACEi’s. Larger studies are needed to determine the dose-duration relationship between ACEi and PC colon polyps, given their widespread use.

The effect of topical ramipril and losartan cream in inhibiting scar formation

The renin-angiotensin system (RAS) plays an important role in scar formation. We have previously shown that oral administration of ramipril and losartan could inhibit scarring. For easier application, here we developed a series of topical ramipril and losartan creams in different concentrations and formulations to explore the effect on scar formation in a C57BL/6 mouse scar model. The harvested scar tissues were analyzed with H&E staining, Masson staining and immunohistochemical staining. We found the group treated with 0.2% losartan urea cream (Prep. 1) or 0.1% ramipril cream (Prep. 2) had significantly smaller scars compared to the negative control, while the proliferation of fibroblasts was less active and the collagen fibers were more regular; both groups showed similar efficacy with the positive control (triamcinolone acetonide urea). We also found that drug transdermalness couldn’t directly determine the efficacy. Our findings indicate that local application of angiotensin converting enzyme inhibitor drugs (ACEIs) and angiotensin receptor blocker drugs (ARBs) can reduce scarring by reducing the expression of collagen I, collagen III, phosphorylated small mothers against decapentaplegic 3 (p-Smad3) and transforming growth factor-β 1 (TGF-β1). This may provide new insight on scar treatment in clinic.

A Glucose-Dependent Pharmacokinetic/ Pharmacodynamic Model of ACE Inhibition in Kidney Cells

Diabetic kidney disease (DKD) is a major cause of renal failure. Podocytes are terminally differentiated renal epithelial cells that are key targets of damage due to DKD. Podocytes express a glucose-stimulated local renin-angiotensin system (RAS) that produces angiotensin II (ANG II). Local RAS differs from systemic RAS, which has been studied widely. Hyperglycemia increases the production of ANG II by podocyte cells, leading to podocyte injury. Angiotensin-converting enzyme (ACE) is involved in the production of ANG II, and ACE inhibitors are drugs used to suppress elevated ANG II concentration. As systemic RAS differs from the local RAS in podocytes, ACE inhibitor drugs should act differently in local versus systemic contexts. Experimental and computational studies have considered the pharmacokinetics (PK) and pharmacodynamics (PD) of ACE inhibition of the systemic RAS. Here, a PK/PD model for ACE inhibition is developed for the local RAS in podocytes. The model takes constant or dynamic subject-specific glucose concentration input to predict the ANG II concentration and the corresponding effects of drug doses locally and systemically. The model is developed for normal and impaired renal function in combination with different glucose conditions, thus enabling the study of various pathophysiological conditions. Parameter uncertainty is also analyzed. Such a model can improve the study of the effects of drugs at the cellular level and can aid in development of therapeutic approaches to slow the progression of DKD.

Biocatalytic Synthesis of Angiotensin–converting Enzyme (ACE) Inhibitor Drug Precursors Using Membrane Bioreactor: A Review

Over the past decade, the production of angiotensin–converting enzyme (ACE) inhibitor drug intermediates has become increasingly important in the pharmaceutical industry. The most significant clinical application of ACE inhibitors is in the management of hypertension and cardiovascular diseases, particularly congestive heart failure (CHF). A number of chemical methods have been reported thus far for the synthesis of ACE inhibitor precursors. However, chemical methods generally suffer from process complexity, high cost, and environmental pollution. On the other hand, enantiomerically pure ACE inhibitor drug precursors can be obtained elegantly and efficiently by employing biocatalytic methods, where it appears to be the most attractive process in terms of potential industrial applications and green chemistry. In the recent past, membranes are expeditiously used in the enzyme–catalyzed synthesis of optically active pharmaceutical compounds on laboratory and industrial scales, being incorporated in membrane bioreactor system. This technique can be applied for the repeated use of the enzymes in the synthesis via retention or immobilization, especially when dealing with costly biocatalysts. Herein we review the enzymatic synthesis of vital ACE inhibitor drug precursors as potentially useful intermediates in the synthesis of pharmaceutical products, in environmentally friendly condition, using membrane bioreactor for biotransformation.

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study.

Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-β and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-β, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45-84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than -950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders. Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema.

RAS Genetic Variants in Interaction with ACE Inhibitors Drugs Influences Essential Hypertension Control

Essential Hypertension (EH) is a common disorder associated with increased cardiovascular morbidity and mortality in Malaysia. To investigate how genetic polymorphisms of the renin-angiotensin-aldosterone system (RAS) influence EH control with angiotensin-converting enzyme inhibitor drugs (ACEI). A case-control, cross-sectional population-based nested study (n=142) included hypertensive subjects treated with ACEI drugs, either lisinopril or enalapril (20mg, once daily) as monotherapy for 24weeks. In total seven possible polymorphisms of RAS genes were genotyped. The association between those polymorphisms and the changes in blood pressure were observed in the 24week treatment. Statistically significant associations of I, G, T, M and G alleles of ACE (I/D, G2350A), AGT (M235T, T175M and G-6A) respectively were observed in essential hypertensive subjects. The decrease in systolic blood pressure and diastolic blood pressure after 24weeks of treatment of the patients carrying II, GG, and TT genotypes were greater than the groups carrying DD, AA, MM, MM and GG of I/D, G2350A, M235T, T174M and G-6A genotypes respectively. In contrast, No significant difference was observed between renin gene polymorphisms (Bg/I and MboI) and hypertensives. Although this study shows a possible association of polymorphisms of RAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.

Electrochemically reduced graphene and iridium oxide nanoparticles for inhibition-based angiotensin-converting enzyme inhibitor detection

In this work, a novel biosensor based on electrochemically reduced graphene oxide and iridium oxide nanoparticles for the detection of angiotensin-converting enzyme inhibitor drug, captopril, is presented. For the preparation of the biosensor, tyrosinase is immobilized onto screen printed electrode by using 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide and N-Hydroxysuccinimide coupling reagents, in electrochemically reduced graphene oxide and iridium oxide nanoparticles matrix. Biosensor response is characterized towards catechol, in terms of graphene oxide concentration, number of cycles to reduce graphene oxide, volume of iridium oxide nanoparticles and tyrosinase solution. The designed biosensor is used to inhibit tyrosinase activity by Captopril, which is generally used to treat congestive heart failure. It is an angiotensin-converting enzyme inhibitor that operates via chelating copper at the active site of tyrosinase and thioquinone formation. The captopril detections using both inhibition ways are very sensitive with low limits of detection: 0.019µM and 0.008µM for chelating copper at the active site of tyrosinase and thioquinone formation, respectively. The proposed methods have been successfully applied in captopril determination in spiked human serum and pharmaceutical dosage forms with acceptable recovery values.

Treatment of IgA nephropathy based on the severity of clinical and histological features.

Immunoglobulin A (IgA) nephropathy (IgAN) represents a common glomerular disease treated by various therapeutic regimens. We studied 50 IgAN patients to determine the effect of different regimens selected according to severity of the disease on the clinical outcome of patients over a follow-up period of five years. Patients with normal renal function and proteinuria <1 g/24-h received no treatment (Group A, n = 6). Thοse with normal renal function, proteinuria >1 g/24-h and mild to moderate histological lesions received angiotensin-converting enzyme inhibitors (ACEi) and corticosteroids (Group B, n = 23). Patients with baseline serum creatinine (Scr) <2.5 mg/dL, proteinuria >3.5 g/24-h and severe histological lesions received ACEi, corticosteroids and other immunosuppressive drugs (Group C, n = 18). Finally, patients with Scr >2.5 mg/dL, glomerulosclerosis and tubulointerstitial fibrosis received ACEi and fish oil (Group D, n = 3). Doubling of baseline Scr was observed in nine (18%) patients; two (8.7%) patients from Group B, five (27.7%) patients from Group C and two (66.7%) patients from Group D. Of the seven (14%) patients who reached end-stage renal disease, one (4.3%) patient was from Group B, four (21.0%) patients were from Group C and two (66.7%) patients were from Group D. Reduction of proteinuria was observed in all (100%) patients from Group B and in 15 (83.3%) patients from Group C. Adverse reactions occurred in three of 18 (16%) patients treated with immunosuppressive drugs. The choice of therapeutic regimen used in the treatment of patients with IgAN could be based on the severity of clinical and histological involvement in order to achieve the maximum effect with the least of adverse reactions.

A crossover randomized comparative study of zofenopril and ramipril on cough reflex and airway inflammation in healthy volunteers.

BackgroundPersistent dry cough is a well known unwanted effect of Angiotensin-Converting Enzyme inhibitors (ACE-i). Animal studies have shown that the ACE-i zofenopril has a less tussigenic effect compared to the widely used ACE-i ramipril. The aim of this study was to compare cough sensitivity to inhaled tussigens, as well as spontaneous cough in response to the administration of zofenopril and ramipril in healthy volunteers; pharmacokinetic (PK) data of both zofenopril and ramipril, as well as their respective active forms, zofenoprilat and ramiprilat, was also collected.MethodsForty healthy volunteers were enrolled in a randomized crossover study. Patients were administered zofenopril calcium salt (test drug) coated tablets, 30 mg daily dose or ramipril (reference drug) tablets, 10 mg daily dose, for 7 consecutive days in two periods separated by a 21-day wash-out period. Cough sensitivity to capsaicin and citric acid was assessed as the concentration of each tussigenic agent causing at least 2 (C2) or 5 coughs (C5); spontaneous cough was also monitored throughout the study. PK parameters of zofenopril, ramipril and their active forms, were collected for each of the two study periods. Airway inflammation, as assessed by fractional exhaled nitric oxide (FeNO) and bradykinin (BK) levels, were measured prior to and following each treatment period.ResultsRamipril, but not zofenopril, increased (p < 0.01) cough sensitivity to both tussigenic agents as assessed by C2. With citric acid, C5 values calculated after both ramipril and zofenopril administration were significantly (p < 0.05 and p < 0.01, respectively) lower than corresponding control values. With both ACE-i drugs, spontaneous cough was infrequently reported by subjects.Zofenopril/zofenoprilat PK analysis showed higher area under the curve of plasma concentration, τ values (ng/ml x h) than ramipril/ramiprilat (zofenopril vs. ramipril, 84.25 ± 34.47 vs. 47.40 ± 21.30; and zofenoprilat vs. ramiprilat, 653.67 ± 174.91 vs. 182.26 ± 61.28).Both ACE-i drugs did not affect BK plasma levels; in contrast, ramipril, but not zofenopril, significantly increased control FeNO values (from 24 ± 9.6 parts per billion [PPB] to 33 ± 16 PPB; p < 0.01).ConclusionsZofenopril has a more favourable profile when compared to ramipril as shown by a reduced pro-inflammatory activity and less impact on the cough reflex.

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo.

Factores implicados en el desarrollo de vasoplejía tras cirugía cardiaca con circulación extracorpórea. Estudio prospectivo observacional

The incidence and risk factors for vasoplegia in the early postoperative period and at 24h are investigated in patients subjected to cardiopulmonary bypass surgery. Vasoplegia following cardiac surgery with cardiopulmonary bypass is associated with a high morbimortality. The risk factors described emerged from retrospective, non-controlled studies. Observational prospective study of 188 consecutive patients subjected to cardiac surgery with cardiopulmonary bypass in a single hospital between November 2011 and May 2012. Emergency surgery or complex procedures were excluded. Vasoplegia was assessed during the immediate postoperative period, and at 24h after surgery, and was defined as a mean arterial pressure below 50mmHg, and the need for a noradrenaline perfusion of more than 0.08μg/kg/min, monitored by cardiac output and systemic vascular resistances. The anaesthetic and cardiopulmonary bypass protocols, as well as haemodynamic management, were the same in all patients. Almost half (48%) of patients had vasoplegia in the immediate postoperative period, and 34% at 24h. Risk factors for immediate vasoplegia development were preoperative use of angiotensin converting enzyme inhibitor drugs, a mean arterial pressure<50mmHg immediately after beginning cardiopulmonary bypass, duration of aortic clamping as well as the cardiopulmonary bypass, and minimum temperature in cardiopulmonary bypass. Vasoplegia at 24h after surgery was correlated to preoperative angiotensin converting enzyme inhibitor drug treatment and cardiopulmonary bypass duration. The incidence of vasoplegia after cardiac surgery with cardiopulmonary bypass is high during the first 24 postoperative hours. Preoperative treatment with angiotensin converting enzyme inhibitor and the mean arterial pressure at the beginning of cardiopulmonary bypass are the more easily controllable risk factors. In patients arriving to surgery with those drugs, treatment or prevention of vasoplejia should be planned.

Unnecessary surgery for acute abdomen secondary to angiotensin-converting enzyme inhibitor use

Acute abdominal pain is the reason for 5% to 10% of all emergency department visits. In 1 in every 9 patients, operated on for an acute abdomen, laparotomy is negative. In a minority of patients, the acute abdomen is caused by side effects of medication. We present a case of unnecessary abdominal surgery in a patient with acute abdominal pain caused by intestinal angioedema (AE), which was eventually due to angiotensin-converting enzyme inhibitor (ACE-i) use. We hope that this case report increases awareness of this underdiagnosed side effect. Emergency department physicians, surgeons, internists, and family physicians should always consider ACE-i in the differential diagnosis of unexplained abdominal pain. Since early withdrawal of the medication causing intestinal AE can prevent further complications and, in some cases, needless surgery, we propose an altered version of the known diagnostic algorithm, in which ACE-i and nonsteroidal anti-inflammatory drugs–induced AE is excluded at an early stage.

L’angiœdème laryngé induit par les médicaments interférant avec le métabolisme de la bradykinine

Angiotensin converting enzyme inhibitors (ACEi) provoke a specific angioedema (AE). This reaction is bradykinin-mediated and consequently it is resistant to corticosteroids, antihistamines and adrenalin. ACEi drugs induce unpredictable AE which can appear some months after the beginning of the treatment. It is a rare complication (0.68% of ACEi drug users) but nevertheless a very dangerous one; in cases with laryngeal AE, the risk of death is 20–25% if the patient doesn’t receive specific treatment. Diagnosis is difficult because there is still no rapid laboratory-based diagnosis, but nevertheless necessary because effective treatments (icatibant, pdhC1INH) are available.

Expression of angiotensin-converting enzyme mRNA gene in the kidneys of patients with glomerulonephrites

A little is known about the behavior of the renin-angiotensin system (RAS) in glomerulo-nephritis (GN), although it is activated in other models of injury. To study renal angiotensin-converting enzyme (ACE) messenger ribonucleic acid (mRNA) gene expression in patients with GN to determine its role in the disease process and other factors that may influence the course of the disease and the prognosis, e.g. treatment with ACE inhibitor (ACEI) drugs, we studied 20 patients with GN allocated to two groups: ten patients received an ACEI drug and ten patients did not receive ACEI in addition to a control group of ten healthy subjects. Routine and special laboratory investigation, histopathological studies and quantitative polymerase chain reaction analysis for renal ACE mRNA were done for both the study and the control groups. There was a statistically significant increase in ACE mRNA gene expression in the GN groups than in control group, but no statistically significant difference in ACE mRNA gene expression between the patients group that received and the group that did not receive ACEI. A significant correlation was found between the ACE mRNA gene expression and the mean blood pressure, serum creatinine, blood urea nitrogen and 24-h urinary protein. In conclusion, a higher level of ACE mRNA gene expression in patients suffering from GN may suggest a role of the RAS in the process of GN, perhaps contributing to glomerular hypertrophy and matrix overproduction. The use of ACEI drugs possibly slows the rate of progression of renal failure and plays a role in controlling the pathophysiology.

Chronic urticaria and use of statins

To the Editor, I read with interest the consensus guidelines on chronic urticaria by Steven KW Chow and colleagues [1] but have reservations with the statement that angiotensin converting enzyme inhibitors (ACEIs) should usually be avoided in chronic urticaria with or without angioedema. Although the EAACI/GA2LEN/EDF/WAO position paper does allude to the fact that ACEIs come second to non-steroidal anti-inflammatory drugs in eliciting and aggravating urticaria [2], the level of evidence to support this statement was not provided. Yet another consensus statement on the management of urticaria by Godse KV et al. [3] does not mention ACEIs as a possible trigger for urticaria. The incidence of urticaria to the ACEI drug enalapril was reported at 0.3% (32 of 12,543 patients) in a 12 months post-marketing surveillance study, but the report also mentioned that this necessitated withdrawal of the drug only in 5 cases and 6 other cases of urticaria were not attributed to enalapril [4]. Dr. Pfeiffer [5] referenced the above paper in a correspondence to a review by Dr. Allen P Kaplan [6] on chronic urticaria and angioedema in The New England Journal of Medicine, but that ACEI drugs can elicit urticaria was not entirely accepted by Dr. Kaplan in his reply [5]. A more commonly prescribed class of drugs that have a higher incidence of urticaria are lipid lowering statins. Manufacturers of statin drugs report the combined incidence of rash and allergic reactions to be 7.7% (data on file; Parke-Davis, USA) that is much higher than that for ACEIs [see Table 1 for published reports; MEDLINE from PubMed, EMBASE, BNI, CINAHL with search terms: 'statin', 'urticaria']. A recently published 10-year study from the French PharmacoVigilance Database reported 7.3% of systemic lupus erythematosus cases associated with statin use [with reporting odds ratio at 1.67 (95% CI 1.02-2.74)] [7]. The mechanisms of statin-induced (autoimmune) urticaria/systemic lupus erythematosus may be related to (1) the proapoptotic nature of the drug (at least the second generation statins) that may release otherwise unaccessible nuclear antigens and subsequent generation of autoantibodies; and (2) statins have been shown to promote a shift from T helper 1 (Th1) to Th2 immune responses that leads to B-cell reactivity and the production of pathogenic autoantibodies [8-10]. Table 1 Reports of statin use with development of urticaria With several consensus guidelines from various clinical groups recommending prophylactic statin therapy, clinicians should be aware of all side effects with these widely prescribed medications.

Fast parameters estimation in medication efficacy assessment model for heart failure treatment.

Introduction. Heart failure (HF) is a common and potentially fatal condition. Cardiovascular research has focused on medical therapy for HF. Theoretical modelling could enable simulation and evaluation of the effectiveness of medications. Furthermore, the models could also help predict patients' cardiac response to the treatment which will be valuable for clinical decision-making. Methods. This study presents a fast parameters estimation algorithm for constructing a cardiovascular model for medicine evaluation. The outcome of HF treatment is assessed by hemodynamic parameters and a comprehensive index furnished by the model. Angiotensin-converting enzyme inhibitors (ACEIs) were used as a model drug in this study. Results. Our simulation results showed different treatment responses to enalapril and lisinopril, which are both ACEI drugs. A dose-effect was also observed in the model simulation. Conclusions. Our results agreed well with the findings from clinical trials and previous literature, suggesting the validity of the model.

P37 Muscle mass in COPD patients receiving angiotensin II receptor blockers and ACE-inhibitors

BackgroundSkeletal muscle dysfunction is well recognised in chronic obstructive pulmonary disease (COPD) and is associated with increased morbidity and mortality. Considerable circumstantial evidence supports a role for renin-angiotensin systems in...

Establishment of three screening models of angiotensin converting enzyme inhibitors

To establish and compare three in vitro screening models of angiotensin converting enzyme inhibitors (ACEI), and provide methodological basis for screening ACEI drugs from Chinese herbal medicine. Three screening models were established using rat serum, pure angiotensin converting enzyme (ACE) and crude extract enzyme from rabbit lung as enzyme sources, respectively, with corresponding testing methods, and captopril as the positive drug. The IC50 of captopril was 2.30 nmol x L(-1) using rat serum as the enzyme; and 1.04 nmol x L(-1) for ACE pure enzyme; and 1.40 nmol x L(-1) for crude extract enzyme from rabbit lung. Results from the three screening models were all in accordance with literature reports. These models can be applied to in vitro pharmaceutical screening. The selection of suitable screening model depend on the experimental situation and the inherent characters of models.

Controlled Drug Delivery System Based on Ordered Mesoporous Silica Matrices of Captopril as Angiotensin-Converting Enzyme Inhibitor Drug

In the present study, captopril-loaded ordered mesoporous SBA-15 silica matrix were produced, functionalized, and characterized to obtain an efficient formulation of controlled drug delivery system. First, the starting SBA-15 materials are examined to verify that their synthesis has been successful considering the structural properties, using XRD, FTIR, and BET methods. Second, the influence of processing parameters of ordered mesoporous matrices for the loading and release of captopril was investigated. The release of captopril was controlled by tailoring the surface properties of the mesoporous silica via functionalization. The loading and release kinetics (in vitro in simulated gastric and intestinal fluids) showed that both of them were affected by the surface properties of the mesoporous silica materials. Such a formulation shows potential as an efficient controlled drug delivery system.

Caring for uninsured patients with diabetes: designing and evaluating a novel chronic care model for diabetes care

Safety net urban hospitals are being overwhelmed by an increasing number of patients with diabetes, who frequently only access the health system through visits to emergency departments and urgent care clinics. It is uncertain whether the chronic care model advocated for diabetes care would be feasible and effective for managing diabetes in an acute care setting. Determine if redesigning the system of care for treating diabetic patients who do not have primary care doctors is feasible, acceptable to patients and effectively lowers patients' haemoglobin A1c, blood pressure and cholesterol levels. Prospective single cohort study. A total of 1098 consecutive diabetic patients presenting to an urgent care clinic at an urban safety net public hospital in Chicago between October 2004 and April 2006 who had a haemoglobin A1c measured at baseline. Adapt the chronic care model for managing diabetes to the acute care setting of an urgent care clinic to manage uninsured patients with diabetes who do not have primary care. Among the 1098 patients, 833 (76%) had a repeat A1c during the 2- to 12-month follow-up period. On average, A1c values decreased by 1.5 percentage points; systolic blood pressure decreased by 9 mmHg; low-density lipoprotein cholesterol decreased 11 points; and weight decreased 2.3 pounds (all: P < 0.001). The percentage using angiotensin-converting enzyme inhibitor drugs increased from 45% to 83%; aspirin use increased from 38% to 83%; and statin use increased from 34% to 76%. This novel chronic care model for diabetes care of uninsured patients without primary care doctors was feasible, acceptable and effective in increasing the quality of diabetes care and decreasing haemoglobin A1c, blood pressure, cholesterol and weight.