Melanocortin receptors in GtoPdb v.2021.3

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development

Melanocortin receptors in GtoPdb v.2023.1

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test. setmelanotide was approved by the US FDA for weight management in patients with POMC, PCSK1 or LEPR defiency, bremelanotide was approved by the US FDA for generalized hypoactive sexual desire disorder in premenopausal women, and NDP-MSH (afamelanotide) was approved by the EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development

Melanocortin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [36]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development

Breast Tumor Cells with PI3K Mutation or HER2 Amplification Are Selectively Addicted to Akt Signaling

Dysregulated PI3K/Akt signaling occurs commonly in breast cancers and is due to HER2 amplification, PI3K mutation or PTEN inactivation. The objective of this study was to determine the role of Akt activation in breast cancer as a function of mechanism of activation and whether inhibition of Akt signaling is a feasible approach to therapy.A selective allosteric inhibitor of Akt kinase was used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate PI3K/Akt signaling: HER2 amplification or PI3K or PTEN mutations in order to determine the biochemical and biologic consequences of inhibition of this pathway. A variety of molecular techniques and tissue culture and in vivo xenograft models revealed that tumors with mutational activation of Akt signaling were selectively dependent on the pathway. In sensitive cells, pathway inhibition resulted in D-cyclin loss, G1 arrest and induction of apoptosis, whereas cells without pathway activation were unaffected. Most importantly, the drug effectively inhibited Akt kinase and its downstream effectors in vivo and caused complete suppression of the growth of breast cancer xenografts with PI3K mutation or HER2 amplification, including models of the latter selected for resistance to Herceptin. Furthermore, chronic administration of the drug was well-tolerated, causing only transient hyperglycemia without gross toxicity to the host despite the pleiotropic normal functions of Akt.These data demonstrate that breast cancers with PI3K mutation or HER2 amplification are selectively dependent on Akt signaling, and that effective inhibition of Akt in tumors is feasible and effective in vivo. These findings suggest that direct inhibition of Akt may represent a therapeutic strategy for breast and other cancers that are addicted to the pathway including tumors with resistant to Herceptin

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

High-Intensity Interval Training for Cardiometabolic Disease Prevention

The 2018 Physical Activity Guidelines Advisory Committee systematically searched existing literature reviews to assess the relationship between high-intensity interval training (HIIT) and reduction in cardiometabolic disease risk.Duplicate independent screenings of 260 articles identified from PubMed®, Cochrane Library, and CINAHL databases yielded suitable data from one systematic review and two meta-analyses. Search terms included a combination of "high intensity" "physical activity/exercise" and "interval training" and outcome-specific terms. The quality of the included reviews was assessed using a tailored version of the AMSTARExBP report on quality. Exposure Subcommittee members graded scientific evidence strength based on a five-criteria rubric and assigned one of four grades: strong, moderate, limited, or not assignable.Moderate evidence indicates that HIIT can improve insulin sensitivity, blood pressure, and body composition in adults with group mean ages ranging from ~20 to ~77 yr. These HIIT-induced improvements in cardiometabolic disease risk factors are comparable with those resulting from moderate-intensity continuous training, and they are more likely to occur in adults at higher risk of cardiovascular disease and diabetes than in healthy adults. Moderate evidence also indicates that adults with overweight or obesity classification are more responsive than adults with normal weight to HIIT-related improvements in insulin sensitivity, blood pressure, and body composition. Insufficient evidence was available to determine whether a dose-response relationship exists between the quantity of HIIT performed and several risk factors for cardiovascular disease and diabetes, or whether the effects of HIIT on cardiometabolic disease risk factors are influenced by age, sex, race/ethnicity, or socioeconomic status.HIIT by adults, especially those with overweight and obesity classification, can improve insulin sensitivity, blood pressure, and body composition, comparable with those resulting from moderate-intensity continuous training

Data Paper. Data Paper

<h2>File List</h2><blockquote> <p>Data files are in ASCII format, tab delimited. No compression schemes were used. Data set consists of 5732 records, not including header row.</p> <p><a href="MOMv3.3.txt">MOMv3.3.txt</a></p> </blockquote><h2>Description</h2><blockquote> <p>The purpose of this data set was to compile body mass information for all mammals on Earth so that we could investigate the patterns of body mass seen across geographic and taxonomic space and evolutionary time.  We were interested in the heritability of body size across taxonomic groups (How conserved is body mass within a genus, family, and order?), in the overall pattern of body mass across continents (Do the moments and other descriptive statistics remain the same across geographic space?), and over evolutionary time (How quickly did body mass patterns iterate on the patterns seen today?  Were the Pleistocene extinctions size specific on each continent, and did these events coincide with the arrival of man?).  These data are also part of a larger project that seeks to integrate body mass patterns across very diverse taxa (NCEAS Working Group on Body size in ecology and paleoecology:  linking pattern and process across space, time and taxonomic scales).  We began with the updated version of Wilson and Reeder’s (1993) taxonomic list of all known Recent mammals of the world (<i>N</i> = 4629 species) to which we added status, distribution, and body mass estimates compiled from the primary and secondary literature. Whenever possible, we used an average of male and female body mass, which was in turn averaged over multiple localities to arrive at our species body mass values.  The sources are line referenced in the main data set, with the actual references appearing in a table within the metadata.  Mammals have individual records for each continent they occur on.  Please note that our data set is more than an amalgamation of smaller compilations.  Although we relied heavily a data set for Chiroptera by K. E. Jones (<i>N</i> = 905), the CRC handbook of Mammalian Body Mass (<i>N</i> = 688), and a data set compiled for South America by P. Marquet (<i>N</i> = 505), these total less than half the records in the current database.  The remainder are derived from more than 150 other sources (see reference table).  Furthermore, we include a comprehensive late Pleistocene species assemblage for Africa, North and South America, and Australia (an additional 230 species). “Late Pleistocene” is defined as approximately 11 ka for Africa, North and South America, and as 50 ka for Australia, because these times predate anthropogenic impacts on mammalian fauna. Estimates contained within this data set represent a generalized species value, averaged across gender and geographic space.  Consequently, these data are not appropriate for asking population-level questions where the integration of body mass with specific environmental conditions is important.  All extant orders of mammals are included, as well as several archaic groups (<i>N</i> = 4859 species).  Because some species are found on more than one continent (particularly Chiroptera), there are 5731 entries.  We have body masses for the following:  Artiodactyla (280 records), Bibymalagasia (2 records), Carnivora (393 records), Cetacea (75 records), Chiroptera (1071 records), Dasyuromorphia (67 records), Dermoptera (3 records), Didelphimorphia (68 records), Diprotodontia (127 records), Hydracoidea (5 records), Insectivora (234 records), Lagomorpha (53 records), Litopterna (2 records), Macroscelidea (14 records), Microbiotheria (1 record), Monotremata (7 records), Notoryctemorphia (1 record), Notoungulata (5 records), Paucituberculata (5 records), Peramelemorphia (24 records), Perissodactyla (47 records), Pholidota (8 records), Primates (276 records), Proboscidea (14 records), Rodentia (1425 records), Scandentia (15 records), Sirenia (6 records), Tubulidentata (1 record), and Xenarthra (75 records).  </p> <p>   <i>Key words</i>: <i>body mass; extinct mammals; late Quaternary; macroecology; taxonomy.</i></p> </blockquote