Clinical application of pulsatility index

Pulsatility index (PI) is defined as the difference between the peak systolic flow and minimum diastolic flow velocity, divided by the mean velocity recorded throughout the cardiac cycle. It is a non-invasive method of assessing vascular resistance with the use of Doppler ultrasonography. It was first introduced in 1974 by Gosling and King and is also known as the Gosling Index. PI as a method of examining macrocirculation has a variety of clinical applications. For instance, in diabetic patients, it has been measured on the common carotid, middle cerebral or renal arteries to help predict complications such as cerebrovascular disease or nephropathy. In hypertensive patients, it has been used to assess complications and assess the chronicity of the disease. To our knowledge, despite the diverse use of this ultrasonographic parameter, there is a deficiency in reports that would comprehensively summarize its clinical applications. Based on our extensive review of the literature and the gathered information, we conclude that pulsatility index (PI) is an easy to obtain parameter with a broad range of both, research and clinical applications. It has been widely used in the assessment of macrocirculation in highly prevalent chronic medical conditions, such as hypertension, both type 1 and type 2 diabetes and thyroid disorders

Journal of Cardiovascular Magnetic Resonance ® , 3(4), 349–360 (2001) Mechanisms of the Effects of Nicorandil in the Isolated Rat Heart During Ischemia and Reperfusion: A 31 P-Nuclear Magnetic Resonance Study

Nicorandil (SG75) is a potent K �-channel activator with an additional nitro moiety. In the present study we investigated the potential mechanisms (K �-channel activation and nitric oxide [NO] release) for the effects of nicorandil on isolated perfused rat hearts during total global ischemia using 31 P-nuclear magnetic resonance. After a 10-min control perfusion, hearts were subjected to treatment with nicorandilcontaining (100, 300, or 1000 µM) buffer for 10 min, 15 min of total global ischemia, and 30 min of reperfusion. At high dose (10 �3 M), nicorandil reduced ATP depletion during ischemia by 26 % compared with untreated hearts. Blockade of K � channels by glibenclamide prevented this protective effect. At all doses (10 �4 to 10 �3 M), nicorandil reduced the accumulation of protons during ischemia compared with untreated hearts (pH 6.22 � 0.03 vs. 6.02 � 0.05 in untreated hearts at the end of ischemia). This effect was preserved after blockade of K � channels by glibenclamide. Hearts treated with nitroglycerine before ischemia also showed reduced proton accumulation. Therefore, NO release accompanied by increased coronary flow before ischemia, which is caused by the nitro moiety of nicorandil and nitroglycerine treatment, results in reduced proton accumulation. During reperfusion, a pro-arrhythmic effect was observed in hearts treated with the nonpharmacologically high dose of nicorandil (1000 µM). Thus, we conclude that the effects of nicorandil are caused Address correspondence and reprint requests to Michael Horn

Restoration of sinus rhythm does not improve peripheral blood flow in hemodynamically stable patients with atrial fibrillation

Background. Atrial fibrillation (AFib) is the most common atrial tachyarrhythmia with multiple negative hemodynamicconsequences. Although there have been many studies on the effects of AFib on cardiac function, very fewhave focused on changes in peripheral circulation during arrhythmia. Therefore, the aim of the present study was todetermine the effect of the reversal of AFib to sinus rhythm (SR) on peripheral blood flow. Material and methods. The forearm blood flow was determined by strain gauge plethysmography (EC 5R, Hokanson,Bellevue, USA) in hemodynamically stable 41 patients aged 63 ± 12 years with paroxysmal or persistent AFib.Venous capacity (VC), venous outflow (VO) and V0.5–2.0 index, arterial inflow (AI) and fast blood flow (FBF) weremeasured. 24 patients underwent successful cardioversion. The assessment of peripheral blood flow, BP and HR wasperformed during arrhythmia and then replicated within 7 day period after restoring of SR. Results. At baseline, plethysmographic parameters, heart rate, systolic and diastolic BP did not differ significantlyfor patients who underwent successful cardioversion vs. in those who failed to restore SR. Conversion of AFib to SRdid not change values of indices characterizing both venous and arterial vessels, values of systolic and diastolic bloodpressure, whereas heart rate was significantly reduced. Conclusions. Restoration of sinus rhythm does not improve peripheral blood flow in hemodynamically stable patientswith AFib in short term observation

Deep drilling reveals massive shifts in evolutionary dynamics after formation of ancient ecosystem

The scarcity of high-resolution empirical data directly tracking diversity over time limits our understanding of speciation and extinction dynamics and the drivers of rate changes. Here, we analyze a continuous species-level fossil record of endemic diatoms from ancient Lake Ohrid, along with environmental and climate indicator time series since lake formation 1.36 million years (Ma) ago. We show that speciation and extinction rates nearly simultaneously decreased in the environmentally dynamic phase after ecosystem formation and stabilized after deep-water conditions established in Lake Ohrid. As the lake deepens, we also see a switch in the macroevolutionary trade-off, resulting in a transition from a volatile assemblage of short-lived endemic species to a stable community of long-lived species. Our results emphasize the importance of the interplay between environmental/climate change, ecosystem stability, and environmental limits to diversity for diversification processes. The study also provides a new understanding of evolutionary dynamics in long-lived ecosystems

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

Systematic Two-Hybrid and Comparative Proteomic Analyses Reveal Novel Yeast Pre-mRNA Splicing Factors Connected to Prp19

Prp19 is the founding member of the NineTeen Complex, or NTC, which is a spliceosomal subcomplex essential for spliceosome activation. To define Prp19 connectivity and dynamic protein interactions within the spliceosome, we systematically queried the Saccharomyces cerevisiae proteome for Prp19 WD40 domain interaction partners by two-hybrid analysis. We report that in addition to S. cerevisiae Cwc2, the splicing factor Prp17 binds directly to the Prp19 WD40 domain in a 1∶1 ratio. Prp17 binds simultaneously with Cwc2 indicating that it is part of the core NTC complex. We also find that the previously uncharacterized protein Urn1 (Dre4 in Schizosaccharomyces pombe) directly interacts with Prp19, and that Dre4 is conditionally required for pre-mRNA splicing in S. pombe. S. pombe Dre4 and S. cerevisiae Urn1 co-purify U2, U5, and U6 snRNAs and multiple splicing factors, and dre4Δ and urn1Δ strains display numerous negative genetic interactions with known splicing mutants. The S. pombe Prp19-containing Dre4 complex co-purifies three previously uncharacterized proteins that participate in pre-mRNA splicing, likely before spliceosome activation. Our multi-faceted approach has revealed new low abundance splicing factors connected to NTC function, provides evidence for distinct Prp19 containing complexes, and underscores the role of the Prp19 WD40 domain as a splicing scaffold