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Angiotensin-converting enzyme (ACE), a zinc metalloprotein, is a central component of the renin–angiotensin system (RAS). It degrades bradykinin and other vasoactive peptides. Angiotensin-converting-enzyme inhibitors (ACE inhibitors, ACEIs) decrease the formation of angiotensin II and increase the level of bradykinin, thus relaxing blood vessels as well as reducing blood volume, lowering blood pressure and reducing oxygen consumption by the heart, which can be used to prevent and treat cardiovascular diseases and kidney diseases. Nevertheless, ACEIs are associated with a range of adverse effects such as renal insufficiency, which limits their use. In recent years, researchers have attempted to reduce the adverse effects of ACEIs by improving the selectivity of ACEIs for structural domains based on conformational relationships, and have developed a series of novel ACEIs. In this review, we have summarized the research advances of ACE inhibitors, focusing on the development sources, design strategies and analysis of structure-activity relationships and the biological activities of ACE inhibitors.

The free-living, non-parasitic nematode Caenorhabditis elegans is a premier model organism for the study of aging and longevity due to its short lifespan, powerful genetic tools, and conservation of fundamental mechanisms with mammals. Approximately 70 percent of human genes have homologs in C. elegans , including many that encode proteins in pathways that influence aging. Numerous genetic pathways have been identified in C. elegans that affect lifespan, including the dietary restriction pathway, the insulin/insulin-like growth factor (IGF) signaling pathway, and the disruption of components of the mitochondrial electron transport chain. C. elegans is also a powerful system for performing drug screens, and many lifespan-extending compounds have been reported; notably, several FDA-approved medications extend the lifespan in C. elegans , raising the possibility that they can also extend the lifespan in humans. The renin–angiotensin system (RAS) in mammals is an endocrine system that regulates blood pressure and a paracrine system that acts in a wide range of tissues to control physiological processes; it is a popular target for drugs that reduce blood pressure, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Emerging evidence indicates that this system influences aging. In C. elegans , decreasing the activity of the ACE homolog acn-1 or treatment with the ACE-inhibitor Captopril significantly extends the lifespan. In Drosophila , treatment with ACE inhibitors extends the lifespan. In rodents, manipulating the RAS with genetic or pharmacological interventions can extend the lifespan. In humans, polymorphisms in the ACE gene are associated with extreme longevity. These results suggest the RAS plays a conserved role in controlling longevity. Here, we review studies of the RAS and aging, emphasizing the potential of C. elegans as a model for understanding the mechanism of lifespan control.

Objective: To determine the impact of multidisciplinary interventions on hospital admission and mortality in heart failure. Design: Systematic review. Thirteen databases were searched and reference lists from included trials and related reviews were checked. Trial authors were contacted if further information was required. Setting: Randomised controlled trials conducted in both hospital and community settings. Patients: Trials were included if all, or a defined subgroup of patients, had a diagnosis of heart failure. Interventions: Multidisciplinary interventions were defined as those in which heart failure management was the responsibility of a multidisciplinary team including medical input plus one or more of the following: specialist nurse, pharmacist, dietician, or social worker. Interventions were separated into four mutually exclusive groups: provision of home visits; home physiological monitoring or televideo link; telephone follow up but no home visits; and hospital or clinic interventions alone. Pharmaceutical and exercise based interventions were excluded. Main outcome measures: All cause hospital admission, all cause mortality, and heart failure hospital admission. Results: 74 trials were identified, of which 30 contained relevant data for inclusion in meta-analyses. Multidisciplinary interventions reduced all cause admission (relative risk (RR) 0.87, 95% confidence interval (CI) 0.79 to 0.95, p  =  0.002), although significant heterogeneity was found (p  =  0.002). All cause mortality was also reduced (RR 0.79, 95% CI 0.69 to 0.92, p  =  0.002) as was heart failure admission (RR 0.70, 95% CI 0.61 to 0.81, p < 0.001). These results varied little with sensitivity analyses. Conclusion: Multidisciplinary interventions for heart failure reduce both hospital admission and all cause mortality. The most effective interventions were delivered at least partly in the home.

Objective Our case–control study aimed to access the potential association of insertion/deletion (I/D) ACE (angiotensin converting enzyme) gene polymorphism with myocardial infarction (MI) risk of occurrence among a sample of Moroccan patients, especially young ones. Results Distribution of I/D ACE gene variant among cases vs controls, showed that healthy controls carried out higher frequency of wild type allele I compared to cases (23.5% vs 21.79% respectively), when cases were carrying higher frequency of mutant allele D (78.21% vs 76.5% for controls). Patients were-after this- divided into two groups of < 45 and > 55 years of age, to investigate whether or not younger patients carried out higher frequency of the mutant allele D, than older ones. As expected, < 45 years old patients carried out more DD genotype than older ones (68.9% vs 54.6% respectively), and higher frequency of mutant allele D (81.08% vs 75% respectively). Besides, a tendency to a positive association was found under the recessive genetic transmission model (OR [95% CI] = 1.85 [0.93–3.69], P = 0.08), suggesting that the I/D ACE polymorphism may be associated with MI occurrence among younger patients (< 45 years of age).

People with hypertension have a high prevalence of insulin resistance and are at relatively high risk of developing type 2 diabetes mellitus. It is becoming increasingly evident that antihypertensive agents have disparate metabolic effects. For example, recent clinical trials indicate that agents that interrupt the renin-angiotensin axis reduce the risk of developing diabetes compared with other classes of antihypertensive agents. Blockade of the effects of angiotensin II might improve blood flow to insulin-sensitive tissues. Furthermore, interruption of the renin-angiotensin system might provide metabolic benefit through such mechanisms as reduced oxidative stress and restored nitric oxide production, which could lead to improved insulin signaling. Alternatively, collective trials suggest that both diuretics and β-blockers accelerate the appearance of new-onset type 2 diabetes mellitus in patients with hypertension. Therefore, the risk of new-onset diabetes-associated cardiovascular risks should be factored into future treatment recommendations for patients who require antihypertensive therapy. This will become even more important as the number of insulin-resistant patients with hypertension increases in parallel with the steady growth in the number of sedentary, obese, and aged persons in our population.

Objective: To evaluate the effects of a nurse based outpatient management programme for elderly patients discharged with heart failure from a university hospital. Design: Patients with heart failure (New York Heart Association class II–IV) and left ventricular systolic dysfunction aged 60 years or more were randomly assigned to follow up within the management programme or to conventional follow up, usually in primary care. Of the 208 participants, 58% were men, mean age was 75 years, and mean ejection fraction 34%. All patients were scheduled for three observational study visits at six month intervals. The primary end point was quality of life (QoL) and secondary end points were hospitalisation and mortality. Results: More patients achieved target doses of angiotensin converting enzyme (ACE) inhibitors in the intervention group than in the control group (82% v 69%, 88% v 69%, and 88% v 74% of recommended target doses at 6, 12, and 18 months of follow up, respectively, p < 0.05 for all). Patients with initial low QoL had a poor prognosis. After a mean 1122 days of follow up, 82% of all patients had been readmitted. There were on average 4.7 readmissions per patient and 66% were due to non-cardiac diagnoses. There were no differences in QoL or health care consumption between the two study groups during follow up. Conclusion: A nurse based management programme is more effective than follow up in primary care in optimising medication for elderly patients with heart failure. However, such a programme does not seem to have a favourable influence on QoL or readmission rate during long term follow up.

Background: There have been only a few reports on the renin-angiotensin system in low birthweight infants; in particular, plasma angiotensin II concentrations have not been studied. Aim: To investigate plasma angiotensin II concentrations in early neonatal infants including low birthweight infants. Methods: Forty six patients were studied, of whom 14 weighed not less than 2500 g (normal birth weight), 16 weighed less than 2500 g but not less than 1500 g (moderately low birth weight), and 16 weighed less than 1500 g (very low birth weight). Blood samples were collected twice, on day 0 and day 7. Angiotensin II concentration was assayed using an enzyme immunoassay kit with a microplate. Results: Geometric means of angiotensin II concentrations on day 7 were 19 pg/ml in the normal birthweight group, 28 pg/ml in the moderately low birthweight group, and 76 pg/ml in the very low birthweight group. The concentrations on day 7 in the very low birthweight group were significantly higher than those in the normal birthweight and moderately low birthweight groups (p  =  0.005, p  =  0.031). There were significant correlations between angiotensin II concentration on day 7 and gestational age (rs  =  −0.4, p  =  0.007) and birth weight (rs  =  −0.36, p  =  0.016). Conclusions: Specific physiological conditions associated with a very low birth weight are thought to be responsible for the increased concentration of angiotensin II on day 7. It is necessary to measure angiotensin II concentration for a longer period after birth and study the factors that could influence it.

The angiotensin-converting enzyme (ACE) gene in humans contains an insertion-deletion polymorphism in its intron 16. Because of its involvement with the renin-angiotensin system, the insertion-deletion polymorphism of the ACE gene has been widely investigated in different populations and in case-control studies. However, similar studies for Arab populations are limited in number. Therefore we have investigated the frequencies of the *I and *D alleles of the ACE gene among Sudanese, Somalis, and Arab nationals of the United Arab Emirates and Oman using previously described methods. Our data indicate a preponderance of the *D allele among the Arab and African populations studied (Sudanese, 0.64; Somalis, 0.73; Emiratis, 0.61; and Omanis, 0.71).

Patients with acute coronary syndrome (ACS) are at high risk for recurrent coronary events, sudden death, and all-cause mortality. Conventional revascularization therapies reduce the risk of further ischemia but do not affect the underlying atherosclerotic disease. Statins have a proven record in the secondary prevention of coronary heart disease. Furthermore, statins have been shown to exert varying degrees of pleiotropic effects, which may stabilize vulnerable atherosclerotic plaques. A compelling body of evidence from randomized controlled trials demonstrates that high-dose, potent statin therapy initiated immediately after an acute coronary event can significantly reduce early as well as longer-term morbidity and mortality. Furthermore, high-dose, potent statin therapy displays a reasonable safety profile. National guidelines now recommend that in patients with ACS, statin therapy should be initiated in hospital prior to discharge, irrespective of baseline low-density lipoprotein cholesterol levels, to improve clinical outcomes. Every effort should be made to ensure all eligible patients with ACS are initiated and maintained on statin therapy.

Approximately 50% of patients with a firm clinical diagnosis of heart failure (HF) have a normal ejection fraction. Some patients have valvular disease, but most have underlying diastolic dysfunction that leads to pulmonary and systemic congestion and signs and symptoms of HF. Although diastolic HF is clinically and radiographically indistinguishable from HF with depressed left systolic ventricular function, knowledge of which patients are at risk of diastolic HF, the common clinical profiles, and the common echocardiographic findings enhances the clinician's ability to diagnose diastolic HF with confidence. The prognostic implications of a diagnosis of diastolic HF and the therapeutic approach to such patients are reviewed.