The synthesis and pharmacological profile of a novel series of 7-methoxy-furo2,3-
cpyridine-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of ...phosphodiesterase type 4 (PDE4). Initial
The synthesis and pharmacological profile of a novel series of 7-methoxy-furo2,3-
cpyridine-4-carboxamides is reported.
A series of bicyclic heteroaryl ring systems was considered as a replacement for the 3-cyclopentyloxy-4-methoxyphenyl moiety in rolipram resulting in the discovery of ...8-methoxyquinoline-5-carboxamides as potent inhibitors of phosphodiesterase type 4 (PDE4).
A series of bicyclic heteroaryl ring systems was considered as a replacement for the 3-cyclopentyloxy-4-methoxyphenyl moiety in rolipram resulting in the discovery of 8-methoxyquinoline-5-carboxamides as potent inhibitors of phosphodiesterase 4.
The authors measured cardiac mass and function to determine whether these changed in patients who were critically ill who were losing large amounts of nitrogen from the body.
The large losses of body ...nitrogen that occur in patients with protein-energy malnutrition are associated with a loss of cardiac mass and function. It is not known if this also occurs in patients who were critically ill who are losing massive amounts of nitrogen.
Once hemodynamically stable, 13 patients who were critically ill underwent sequential measurements of left ventricular mass (LVM) and function, total body nitrogen (TBN), total body potassium, body weight, fat-free mass, and limb muscle mass.
Over a 21-day study period, there was no change in LVM or function despite falls of 14% and 21% in TBN and total body potassium, respectively, a 21% fall in limb muscle mass, and a deterioration in skeletal muscle function by approximately 40%.
In patients who were critically ill, cardiac mass does not decrease and function does not deteriorate after hemodynamic stability has been achieved despite massive losses of protein from the body.
Random numbers are an essential resource to many applications, including cryptography and Monte Carlo simulations. Quantum random number generators (QRNGs) represent the ultimate source of ...randomness, as the numbers are obtained by sampling a physical quantum process that is intrinsically probabilistic. However, they are yet to be widely employed to replace deterministic pseudo random number generators (PRNG) for practical applications. QRNGs are regarded as interesting devices. However they are slower than PRNGs for simulations and are typically seen as clumsy laboratory prototypes, prone to failures and unreliable for cryptographic applications. Here we overcome these limitations and demonstrate a compact and self-contained QRNG capable of generating random numbers at a pace of 8 Gbit/s uninterruptedly for 71 days. During this period, the physical parameters of the quantum process were monitored in real time by self-checking functions implemented in the generator itself. At the same time, the output random numbers were analyzed with the most stringent suites of statistical tests. The analysis shows that the QRNG under test sustained the continuous operation without physical instabilities or hardware failures. At the same time, the output random numbers were analyzed with the most stringent suites of statistical tests, which were passed during the whole operation time. This extensive trial demonstrates the reliability of a robustly designed QRNG and paves the way to its use in practical applications based on randomness.
Among individuals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with ...a BP-lowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system.
Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo.
After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/ 0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p<0.05 for all). Premature discontinuations were more frequent with omapatrilat than with placebo (p<0.001 for 20 mg and 40 mg).
Omapatrilat produced changes in BP, neurohormone and biochemical parameters that were similar for the two doses. The long-term clinical implications of the observed effects are uncertain and a large-scale randomised trial would be required to reliably establish the effects of omapatrilat on the risks of major vascular disease events among patients with coronary heart disease.
In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403–567 ...informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46–52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156–191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two‐point heterogeneity lod score (lod2) tests (dominant and recessive affected‐only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM‐IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = .001) and 2.68 (Combined sample, p=.0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p=.0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow‐up linkage studies of complex disorders can help to direct research efforts toward promising regions.
...discharging these patients back to primary care without echocardiography would deny them and their general practitioners clarification of the type and degree of left ventricular impairment, the ...aetiology of the heart failure, and guidance for treatment. ...we believe that, with the current limited resources for echocardiography, requests should be reserved for cases in which there is the most diagnostic doubt.
The major positive regulatory activity of the human α-globin gene complex has been localized to an element associated with a strong erythroid-specific DNase I hypersensitive site (HS -40) located 40 ...kb upstream of the ζ2-globin mRNA cap site. Footprint and gel shift analyses of the element have demonstrated the presence of four binding sites for the nuclear factor GATA-1 and two sites corresponding to the AP-1 consensus binding sequence. This region resembles one of the major elements of the β-globin locus control region in its constitution and characteristics; this together with evidence from expression studies suggests that HS -40 is a primary element controlling a-globin gene expression.
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