In other situations subjects may desire to reduce their natural s

In other situations subjects may desire to reduce their natural skin colour or the skin darkening caused by exposure to Pomalidomide price intense sun rays. The complexion of the skin is determined by the pigment melanin. Melanocytes are the pigment producing cells that provide photo protection to the skin by synthesizing and distributing the pigment melanin to keratinocytes. These melanocytes are located in the basal layer of

keratinocytes. Melanocytes and keratinocytes are resident population of epidermis and the color of skin is only because of the melanin in keratinocytes which is transferred from melanocytes. Melanin is synthesized and packed in cytoplasmic organelles of melanocytes, called melanosomes and are later transferred to keratinocytes through specialized structures in the melanocytes called dendrites. Since melanocytes are the minor population in the epidermis, the presence of the multiple dendrites facilitates transfer of melanosomes to keratinocytes that surround melanocytes. Movement of the melanosomes along melanocyte dendrites is also necessary for the transfer of melanin

pigment from melanocytes to basal and suprabasal keratinocytes to maintain the normal skin color.1 Melanocyte dendrite formation is regulated Selleck ROCK inhibitor by multiple signaling pathways stimulated by paracrine factors released by keratinocytes.2 The most effective mode of transfer of the melanin to the keratinocytes is governed by the dendritic phenomena of the melanocytes. Abroagating the dendricity of the melanocytes is of great importance for controlling skin colour.3 There are several dendrite inhibitors either crude extracts or pure compounds already reported in the literature. These compounds are benzoquinone group moiety that includes centaureidin,3 methyl-ophiopogonanone B from Ophiopogon japonicus ker-Gawler, 4 and 1, 3-dioxolane derivative of methyl-ophiopogonanone B, 5 berberine derivative, 6 and betuligenol. 7 In our continuous

interest on the isolation of biologically active molecules from medicinal plants for personal care applications,8, 9, 10, 11, 12, 13, 14 and 15 we have undertaken the chemical examination of the leaves of Artocarpus altilis Parkinson. The genus, Artocarpus is small to large evergreen trees, distributed from Sri Lanka, Sitaxentan India to south China and through Malaysia to the Solomon Islands. Nine species are recorded in India. The plant, A. altilis (syn. A. communis) is indigenous to Malaysia and commonly cultivated in South India. It is known as Breadfruit in English, Dephal in Bengali and Seema panasa in Telugu. The fruit is being used culinary preparations, as bread and pudding. The root is used as in controlling diarrhea and dysentery. The root bark is utilized in the treatment of fractures. The petiole is used for eye sores, irritation and itch. 16 The plant is rich source for pectin (5.7%) and also having good jelling properties.

Microbial PAMPs, such as lipopolysaccharides, single-stranded RNA

Microbial PAMPs, such as lipopolysaccharides, single-stranded RNA, and bacterial DNA motifs, bind to a family of PRRs called Toll-like receptors (TLR) on innate immune cells and stimulate antigen processing and presentation [16], [17] and [18]. TLRs are widely expressed on dendritic cells (DC) and other professional APCs such as macrophages and B cells. While some TLRs are expressed on the cell surface and act as sensors for extracellular PAMPs (e.g., lipopolysaccharides), a subset of TLR molecules (TLR3, 7, 8 and 9) are expressed

on endosomal membranes and bind selleck kinase inhibitor nucleic acid-derived molecules, such as single-stranded RNA of viral origin for TLR7 and 8 [19], [20], [21], [22], [23] and [24] and bacterial unmethylated DNA oligonucleotides (ODNs) containing CpG motifs (CpG ODNs) for TLR9 [14], [25], [26], [27] and [28]. TLR ligands of natural and synthetic origin are potent inducers of innate immune responses and have been shown to effectively stimulate the transition from an innate immune response to an adaptive immune SAR405838 molecular weight response. As such, TLR agonists have been evaluated as potential adjuvants in a variety of applications [4]. To date, only one PRR ligand,

3-O-desacyl-4′-monophosphoryl lipid A (MPL), a TLR4 agonist, has been included as an adjuvant in a FDA- or EMA-licensed vaccine. MPL adsorbed onto alum is utilized in the HPV vaccine Cervarix, licensed in the U.S. and Europe [29], and the hepatitis B vaccine Fendrix, licensed in Europe [30]. Imiquimod, a topically administered TLR7 agonist, has been approved for treatment of genital warts, actinic keratosis, and basal cell carcinoma [31]. Other TLR agonists, such as poly(I:C) (TLR3), imidazoquinolines other than imiquimod (TLR7, 8, or 7/8), and CpG ODNs (TLR9), have failed thus far to enter clinical practice as parenteral adjuvants despite a multitude

of over promising data obtained in preclinical and clinical studies [32], [33], [34], [35] and [36]. One of the main reasons for this failure is the delicate balance between the induction of augmented immunogenicity by TLR agonists and safety concerns, which are often related to the generation of systemic inflammatory responses [19], [37], [38] and [39]. Several groups have utilized micro- and nanocarriers, such as virus-like particles, liposomes, and PLGA particles, to encapsulate adjuvants [40], [41] and [42]. Encapsulation of adjuvants reduces systemic exposure of adjuvant and enhances uptake by APCs. Nano-size viruses and particles distribute rapidly to the local draining lymph node where they are taken up by subcapsular macrophages and dendritic cells [41], [43] and [44]. Antigens can also be delivered in particles to target efficient uptake by APCs [36], [41], [45] and [46].

4 U/ml > butanol – 2 7 U/ml Highest levels of activity was obser

4 U/ml > butanol – 2.7 U/ml. Highest levels of activity was observed in hexane according to Baharum et al28 The effect of detergents on lipase production is shown in Fig. 8. Triton X 100 at 1% showed highest lipase activity of 22 U/ml, whereas reduced activity was observed with SDS and hydrogen peroxide. Zhang et.al29 studied the most effective time for inducer addition to Candida rugosa cultures and observed, that addition of Tween 80 at an earlier period of cultivation

i.e 0 or 6 h was more effective than at a later stage say 18 h. Higher levels of lipase production might be due to the substrate forming emulsion so as to present an interfacial area to the enzyme. The strain MK-1, producing lipase was identified as S. hominis. Our results confirms it to be a growth associative model and inducible Selleckchem PARP inhibitor enzyme. Microbial lipases has been shown to be influenced by several factors namely, temperature, pH, oil source, nitrogen, solvent, metal ions, detergents etc. Compounds like oils and surfactants have been described as agents, that increases the production of enzymes with lipolytic activity. Hence, it is essential to optimize the sources. Significant percentage of produced enzyme was on the cell membrane, while the extracellular enzyme represented only about 40%. Surfactants

have the ability to solubilise lipids on the membrane, forming micelles and selleck chemicals llc extracting membrane bound proteins. 30 The most widely used lipid inducer are fatty acids, triacylglycerols and some esters. Our results demonstrated, increased extracellular lipolytic activity

about with Triton X100, Tween 80, each one by a different mechanism. First, by allowing a release of membrane bound enzymes without causing too much cell damage and the second, by favouring lysis, which triggers the release of both membrane and intracellular protein. As a consequence, the extracellular lipolytic activity is considerably increased. Thus it is not necessary to use techniques like ultrasounds to achieve cell lysis. Bacterial strains are generally used, as they offer higher activities, compared to yeasts and tend to have neutral/alkaline pH optima and are thermo stable. Present study showed, that Ca2+play an important role in influencing the structure and function of enzyme. The S. hominis lipase identified strain S. hominis MTCC 8980/JX961712,when supplied with essential nutrients showed moderate levels of lipase production. To conclude, highest lipase production of 22.3 U/ml was observed at 40 °C and 14.7 U/ml at pH7. Obtained results confirms, that Staphylococcus lipases are more specific to long chain fatty acids. Hence, this strain can be a better source for the increased production of lipase by inducing genetic manipulation. The author has none to declare. The author thank Dr. Tapan Chakravarthy, Microbial Type Culture Collection, Institute of Microbial Technology, Chandigarh, India for identifying the organism.

Moreover, the rat mesenteric

artery reportedly does not e

Moreover, the rat mesenteric

artery reportedly does not express functional NMDArs (51). (±)Ketamine racemate has been reported to inhibited NR1/NR2A and NR1/NR2B channels with IC50 values of 13.6 ± 8.5 and 17.6 ± 7.2 μM, respectively, whereas S(+)-ketamine inhibited NR1/NR2A and NR1/NR2B with IC50 values of 4.1 ± 2.5 and 3.0 ± 0.3 μM, respectively (52). The IC50 values of (+)MK801 and (−)MK801 for inhibiting channels with the NR1 subunit and various NR2 subunit complexes (NR1/NR2X) ranged LGK974 from 9–38 nM and from 32–354 nM, respectively. These IC50 values for inhibiting NMDArs are distinct from those for inhibiting Kv of RMASMCs. The pKa of MK801 is 8.37, and thus approximately 94% of MK801 exists in its protonated, positively charged form at pH 7.2 (the pH of the pipette solution). The results of this study showed that MK801 inhibition of Kv-channel currents was completely voltage-independent (Fig. 3), which suggests that the MK801-binding site of Kv channels is not affected by the sensing of the transmembrane potential, unlike in the case find more of the binding sites for open-pore blocking agents. In this study, we did not examine whether an extra-

or intra-cellular site is responsible for the MK801-Kv channel interaction, which warrants future investigation. As described above, MK801 is a potent NMDAr inhibitor. NMDAr is a glutamate receptor and glutamate is the brain’s primary excitatory neurotransmitter. NMDAr is an ionotropic receptor that, when activated, causes the influx of Ca2+ and other cations. MK801 blocks the NMDAr in a state- and voltage-dependent manner, because the PCP-binding sites in the NMDAr are accessible to MK801 only when the channel is open or activated. Therefore, the mechanism by which MK801 was determined

to inhibit the Kv channels of RMASMCs in this study differs considerably from the mechanism of MK801 inhibition of the NMDAr channel. Because we examined the effect of MK801 on native Kv-channel currents in RMASMCs in this study, the specific target of MK801 remains unknown. Multimeric heteromers of several Kv-channel subunits such as Kv1.1, Kv1.2, Kv1.5, and Kv2.1 have been reported to contribute to the native Kv-channel currents of vascular smooth Florfenicol muscle (53), (54) and (55). Furthermore, certain auxiliary Kv-channel beta subunits have been reported to contribute to the complexity and heterogeneity of native Kv currents (56) and (57). These Kv-channel subunits play critical roles in variety of excitable and non-excitable cells such as those in the cardiovascular system and in the CNS. Therefore, future studies could examine the effect of MK801 on specific Kv-channel subunits expressed in heterologous cell systems. As we stated above, we have observed that MK801 blocked the Kv1.5 expressed in CHO cells. The blockade of Kv1.5 by MK801 was very similar with that the present study.

Les cas de vascularites à ANCA (anticorps anticytoplasme des poly

Les cas de vascularites à ANCA (anticorps anticytoplasme des polynucléaires neutrophiles) sont très rares. Ils s’observent surtout en cas de traitement prolongé par un dérivé du thiouracile. La présence d’ANCA a été constatée chez

un tiers à deux tiers des sujets soumis à un traitement au long cours par le PTU. S’il est important de préciser que la présence d’ANCA n’est pas nécessairement liée à l’apparition de signes cliniques de vascularite, Obeticholic Acid ic50 leur survenue constitue cependant un facteur de prédiction du risque d’angéite. Dès lors, le recours à une autre thérapeutique doit être envisagé. Les ANCA ont été observés aussi mais plus rarement sous thiamazole, et même chez les basedowiens avant tout traitement. Il n’y a pas d’étude randomisée qui ait définitivement établi la supériorité d’un antithyroïdien en termes d’efficacité, de coût ou de tolérance. Toutefois, il est manifeste que l’activité antithyroïdienne des imidazolines est plus forte. Chez l’enfant, il est déconseillé d’utiliser en première intention les dérivés du thiouracile, du fait de rares cas d’hépatite cytolytique sévère, constatés surtout lors de l’utilisation de PTU

à forte dose. Celles-ci ont conduit à des insuffisances hépatiques définitives, nécessitant une greffe hépatique. Dans les hyperthyroïdies sévères et celles liées aux surcharges iodées (hyperthyroïdies de type 1), l’utilisation préférentielle de PTU a été suggérée selleck kinase inhibitor du fait de sa capacité à réduire essentiellement la désiodation de T4 en L-NAME HCl T3. Dans ces situations, il faut tenir compte toutefois des altérations

de la désiodation déjà présentes, du fait de la sévérité de l’état général, de l’utilisation éventuelle de la corticothérapie ou du propranolol, ou lorsque l’hyperthyroïdie s’est constituée sous amiodarone ; de plus, la nécessité de fortes doses d’antithyroïdiens légitime aussi l’utilisation possible des présentations disponibles de thiamazole ou de carbimazole. L’utilisation préférentielle du PTU est recommandée lors de l’initiation des grossesses chez les femmes atteintes de maladie de Basedow soumises à un antithyroïdien. En effet, les aplasies du cuir chevelu, les embryopathies des ATS (omphalocèle, atrésies choanales ou œsophagiennes, malformations diaphragmatique, cardiaque…) n’ont été décrites que sous imidazolines, même si elles ont pu survenir en l’absence de traitement, et chez les sujets indemnes de pathologie thyroïdienne. En revanche, leur survenue n’a pratiquement jamais été rapportée sous dérivés du thiouracile, ce qui légitime l’utilisation du Propylex® si l’initiation d’une grossesse sous ATS est programmée, ou possible (en l’absence de contraception efficace).

This suggests that there may be a greater latent demand for cycli

This suggests that there may be a greater latent demand for cycling in deprived areas, perhaps due to low levels of bicycle ownership resulting from lack of affordability or storage facilities. It is therefore possible that a disproportionate increase in uptake would be seen among deprived populations if BCH docking stations were situated in more deprived areas, as is planned with the expansion of the BCH scheme in spring 2012. Exploration of other potential barriers to usage among deprived populations, including the cost of annual access and the need to pay using a Palbociclib cell line debit or credit card is also warranted. The

use of routinely collected registration data limited what could be studied. It was necessary to use area-level data as a proxy for individual socio-economic deprivation and ethnicity, and it is not known if the observed associations would hold true at the individual level. This is a particular limitation with respect to ethnicity data, which in addition was (like our commuter data) collected almost a decade before the period of this study. In addition, as access keys can be passed between individuals, it is likely that a small number of trips were made by individuals with different demographic ABT-199 in vivo profiles to those who registered. A further limitation is the lack of a clearly defined denominator population, as any individual with a UK debit or credit card could

register to use the scheme. Having data for only a seven month period meant it was not possible to study temporal trends, particularly as usage levels are likely to be highly affected

by the seasons. The health benefits of cycling are well known, and public bicycle sharing schemes are becoming a popular way of promoting cycling in urban environments. Our study has shown that London’s public bicycle sharing scheme is being well used, but that usage is not equitably distributed throughout the population. Oxalosuccinic acid Specifically, women and those living in deprived areas are less likely to register to use the scheme. Amongst those who did register, however, usage was actually higher among those living in deprived areas after adjusting for the fact that those areas were less likely to be close to a BCH docking station. This suggests that the scheme may be meeting a currently unmet need for access to bicycling in deprived communities. Policy makers should consider the health benefits that could be gained from expanding the scheme into deprived areas, and from investigating other means to increase uptake of the scheme among women and those on low incomes. FO conducted this independent research during an MSc funded by the UK National Health Service (NHS)’s postgraduate public health training programme. AG supervised the research during a post-doctoral research fellowship supported by the UK National Institute for Health Research (NIHR).

Furthermore, only a slight cross-reactivity to the HA of a conven

Furthermore, only a slight cross-reactivity to the HA of a conventional H1N1 strain (PR/08/34) was detected in this assay indicating the specificity for the

novel swine flu HA (data not shown). Therefore, a robust selleck kinase inhibitor and consistent antibody response depended on the use of codon-optimized expression plasmids (Fig. 4). For pandemic viral infections such as the 2009 H1N1 swine flu, it is highly desirable to develop vaccines which can be easily adapted to the new circulating strains and can be rapidly deployed in a predictable and reproducible manner. DNA vaccines seem to be particularly advantageous in these respects since production and purification of plasmid DNA is well established. Importantly, previous experience with production of DNA vaccines suggests that changes in the sequence encoding the vaccine antigen have minimal effect on the production process. Thus manufacturing procedures developed for one influenza vaccine can be readily and predictably adapted for use against novel strains. Since it is known that HA expression plasmids can protect mice from a lethal challenge with A/PR/8/34 (H1N1)

[2] and [20], we evaluated swine origin H1N1-derived HA expression plasmids administered using a DNA electroporation system in Balb/c mice. In contrast to the selleckchem results of the studies mentioned above, the immune responses induced by plasmids containing the wildtype sequence were low with substantial variation from animal to animal. Although polyfunctional CD4 responses could be detected in all vaccinees, CTL responses and HA-specific antibodies were found in only half of the recipients. Codon-optimized DNA vaccines against different influenza strains such as avian H5N1 or human H3 variants have been reported to enhance protective efficacy in mice, chickens and humans [1], [8] and [21]. In agreement with these studies, codon-optimization of a HA expression plasmid derived from the novel swine origin H1N1 virus also significantly enhanced

the immunogenicity of the DNA vaccine. Interestingly, the antigen-specific Fossariinae CD4 response was similar to that achieved using to the WT plasmids, but the CD8 responses and antibody levels were significantly enhanced. Furthermore, the responses were consistent among all animals in this group and included polyfunctional CD8 T-cells. These polyfunctional CD8 T-cells seem to correlate well with protection in a number of viral infections [22] and [23]. The dichotomy between the CD4 and CD8 responses was quite surprising, since the increased expression level resulting from codon-optimization should affect both responses to a similar extent as has been previously reported in studies of HIV and HPV DNA vaccines [9] and [24]. This suggests that HA expression of swine origin H1N1 virus is restricted by a different mechanism than genes of HIV and HPV.

In Mexico, Russia and Chile, current and former government employ

In Mexico, Russia and Chile, current and former government employees represented 67%, 50% and 42% of respondents, HA-1077 cell line respectively, compared to 20–30% of respondents in other countries. Other respondents included clinicians (29%), academics (23%), members of civil society (6%), vaccine manufacturers (2%), and international organization representatives (2%). Among those not interviewed, 72% did

not respond to interview invitations, 15% were unable to participate due to travel, 11% stated they were not experts on hepatitis A, and 2% could not be conducted without permission in Russia. Epidemiologic data from the literature were compared with interviewees’ general perceptions of data availability and risk of hepatitis A disease (Table 2). There was strong agreement between the literature and interviewees’ perceptions of the ample epidemiologic evidence on hepatitis

A in find more South Korea (75 articles) and Taiwan (65 articles). Many Korean interviewees mentioned epidemiologic data including disease burden and infection source of hepatitis A. In Taiwan, a number of interviewees expressed confidence in the country’s surveillance system: “We have disease burden and reported cases, very excellent surveillance.” Published data in South Korea and Taiwan show a downward shift in population seroprevalence over time and trends toward infection at older ages [4], [5], [6] and [7]. A number of Korean studies showed most people aged 10–29 have no antibodies against hepatitis A virus [6], [8], [9], [10] and [11], a trend also mentioned in Taiwan. Recent outbreaks were reported in both countries (2007 in Taiwan, 2008–9 in South Korea) [12], [13], [14] and [15]. In Chile and Russia, the majority of interviewees suggested that routine surveillance provided reasonable epidemiological data on hepatitis A, but recent data were not verified from the literature review. Many Chilean respondents were positive about the surveillance data, and our review found sufficient literature through the 1990s documenting the transition

to lower endemicity [16], [17], [18], [19], [20], [21] and [22]. The most recent hepatitis A specific data, however, those were from 2001, with only two studies [23] and [24] examining the changing epidemiology of hepatitis A and the potential threat it poses. Although the Chile Ministry of Health reports incidence data from 1975 to 2011, all hepatitis cases are combined, leaving doubts as to the specific role of hepatitis A: “We don’t have routine hepatitis A tested. Typing is for B only, and if not B, then “non-B.” Overall, respondents in Chile reported a high level of confidence that water and sanitation improvements had largely addressed disease, except for a small number of areas. In Russia, several respondents reported that disease burden data is available and cited numbers of cases by region and year; however, we could not identify such data through the literature review.

27 Therefore, the results obtained from the present fluorescence

27 Therefore, the results obtained from the present fluorescence studies will also help to check any impurities present in fruit powder of A. bilimbi. Preliminary phytochemical and HPTLC analysis

showed presence of different phytochemical compounds such as carbohydrates, proteins, amino acids, tannins, hydrolysable tannins, bitter principles, essential oils, valepotraites, coumarins, flavonoids and terpenes, which could make the fruits useful for treating different ailments. Thus the preliminary screening tests may be useful in the detection of the bioactive principles and subsequently may lead to the drug discovery and development.25 Neratinib mouse HPTLC is one of the simplest and modern technique available today, which provides a chromatographic fingerprint and is suitable for confirming the identity and purity of plants and for detecting adulteration and substitution. HPTLC fingerprint profile along with their recorded Rf values, can serve as reference standard for further research on the medicinal properties of the plant. 24 Plant materials are used throughout developed and developing countries as home remedies, over-the-counter drug products and raw materials for the pharmaceutical industry and represent a substantial proportion of the global herbal drug market. Therefore it is essential to ensure reproducible quality of herbal products.

Thus in recent years there has been an emphasis on standardization of medicinal plants of AZD8055 mouse therapeutic potential. Despite the modern techniques, identification and evaluation of plant drugs

by pharmacognostical studies is still more Carnitine palmitoyltransferase II reliable, accurate and inexpensive means. Since A. bilimbi L. fruits are known for its various medicinal properties, the present study could be useful to supplement information with respect to its identification, authentication and standardization. The information generated can also be useful for preparation of monograph of the plant, which could be incorporated in the preparation of Indian Herbal Pharmacopoeia. All authors have none to declare. “
“Among the different biological agents, laccases represents an interesting group of oxidative enzymes owing to their great potential for biotechnological and environmental applications.1 Laccases (p-benzenediol: oxygen oxidoreductase, EC are multi-copper containing enzymes belonging to the family of enzymes called blue copper proteins, with a copper content varying from two to four atoms per laccase molecule. 2 This enzyme catalysis the oxidation of a broad range of compounds as well as some inorganic ions coupled to the reduction of molecular oxygen to water. 3, 4 and 5 Laccase-mediated system has been applied to numerous processes such as pulp delignification, 6 textile dye decolourization, 4 food industry, 7 development of biosensors and biofuel cells, 8 bioremediation of xenobiotics, 9 synthetic chemistry 10 and cosmetic and dermatological preparations.

Noel Bairey Merz Cardiac Syndrome X (CSX), characterized by angin

Noel Bairey Merz Cardiac Syndrome X (CSX), characterized by angina-like chest discomfort, ST segment depression during exercise, and normal epicardial coronary arteries at angiography, is highly prevalent in women. CSX is not benign, and linked to adverse cardiovascular outcomes and a poor quality of life. Coronary microvascular and endothelial dysfunction and abnormal cardiac nociception have been implicated in the pathogenesis of CSX. Treatment includes life-style modification, anti-anginal, anti-atherosclerotic, and anti-ischemic medications. Non-pharmacological options include cognitive behavioral therapy, enhanced external buy BTK inhibitor counterpulsation, neurostimulation, and stellate ganglionectomy.

Studies have shown the efficacy of individual treatments but guidelines outlining the best course of therapy are lacking. Index 479 “
“An error was made in an article published in the November

2013 issue of Cardiology Clinics (Volume 31, Issue 4) on page 581. “Durable Mechanical Circulatory Support in Advanced Heart Failure: A Critical Care Cardiology Perspective” by Anuradha Lala, MD, and Mandeep R. Mehra, MD, should have included the following disclosure: MRM is a consultant with Thoratec, chair of the REVIVE-IT DSMB (a National Heart, Lung, and Blood Institute-sponsored trial with Thoratec as the device sponsor) and editor of the Journal of Heart and Lung Transplantation. In addition he consults for Boston Scientific, Medtronic, St. Jude Medical, Baxter, the American Board of Internal Medicine, and the National TSA HDAC concentration Institutes of Health. “

J. Eisen Longjian Liu and Howard J. Eisen Heart failure (HF) is typically a chronic disease, with progressive deterioration occurring over a period of years or even decades. HF poses an especially large public health burden. It represents a new epidemic of cardiovascular disease, affecting nearly 5.8 million people in the United States, and over 23 million worldwide. In the present article, our goal is to describe the most up-to-date epidemiology of HF in the United States and worldwide, and challenges facing HF prevention and treatment. Frances L. Johnson Heart failure is a clinical syndrome that is heterogeneous crotamiton in both pathophysiology and etiology. This article describes some of the common mechanisms underlying heart failure, and reviews common causes. Informative diagnostic testing is reviewed. Gabriel Sayer and Geetha Bhat The renin-angiotensin-aldosterone system (RAAS) plays a critical role in the pathophysiology of heart failure with reduced ejection fraction (HFrEF). Targeting components of the RAAS has produced significant improvements in morbidity and mortality. Angiotensin-converting enzyme (ACE) inhibitors remain first-line therapy for all patients with a reduced ejection fraction. Angiotensin-receptor blockers may be used instead of ACE inhibitors in patients with intolerance, or in conjunction with ACE inhibitors to further reduce symptoms.