Noninvasively assessed pulsatility of ascending aortic pressure waveform is associated with the presence of coronary artery narrowing

Several hemodynamic indices, measured invasively in the ascending aorta during routine angiography, are related to the presence and severity of coronary atherosclerosis. Radial artery tonometry, when combined with a validated transfer function, offers the possibility of noninvasive assessment of central arterial pressure. We aim to evaluate the association between noninvasive indices of aortic or radial pressure waveforms and the presence of a significant coronary stenosis. Patients who underwent elective coronary angiography were studied (110 men, 91 women, mean age 53 ± 0.9 years). Noninvasive measurement of their central hemodynamics was performed by analysis of the aortic pressure waveform derived from the radial artery. An increase in aortic fractional pulse pressure was associated with coronary artery narrowing or previous myocardial infarction. After multivariate adjustment, the odds ratio and confidence intervals (CI) of having a significant coronary aortic stenosis was 1.72 (95% CI, 1.1–2.7) and of previous myocardial infarction 1.6 (95% CI, 1.1–2.2). An increase in noninvasively assessed aortic fractional pulse pressure, but not of the peripheral index is significantly associated with the presence of coronary artery disease.     

Inhibition of Kupffer cell activity induces hepatic triglyceride synthesis in fasted rats, independent of lipopolysaccharide challenge

BACKGROUND: Lipopolysaccharides (LPS), cleared from the blood by Kupffer cells, induce hypertriglyceridemia. AIMS: To test the hypothesis that GdCl(3), through inhibition of large Kupffer cell activity, modulates LPS-induced hyperlipidemia in rats. METHODS: Male Wistar rats received a single intravenous injection of GdCl(3)(10 mg/kg) or saline, 24 h before intraperitoneal LPS (1.5 mg/kg) administration. Serum and hepatic lipids as well as activity of key enzymes controlling fatty acid synthesis and esterification in liver tissue were measured. The incorporation of labeled precursors into lipids was assessed in cultured precision-cut liver slices. RESULTS: GdCl(3) does not prevent hypertriglyceridemia occurring in LPS-treated rats. Surprisingly, GdCl(3) per se is able to promote triglycerides accumulation in the liver tissue, an effect related to an increase in hepatic fatty acid esterification. Such an effect also occurs in rats receiving a dietary supplementation with glycine (5%) known to inhibit Kupffer cell secretory capacity. CONCLUSIONS: Large Kupffer cell inhibition does not prevent LPS-induced hypertriglyceridemia and even leads to a metabolic shift of fatty acids towards their esterification and accumulation in the liver tissue, suggesting that Kupffer cells play a role in the regulation of lipid metabolism of the adjacent hepatocytes, independent of any inflammatory stimulus.     

Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases

In man, mutations in different regions of the prion protein (PrP) are associated with infectious neurodegenerative diseases that have remarkably different clinical signs and neuropathological lesions. To explore the roots of this phenomenon, we created a knock-in mouse model carrying the mutation associated with one of these diseases [Creutzfeldt–Jakob disease (CJD)] that was exactly analogous to a previous knock-in model of a different prion disease [fatal familial insomnia (FFI)]. Together with the WT parent, this created an allelic series of three lines, each expressing the same protein with a single amino acid difference, and with all native regulatory elements intact. The previously described FFI mice develop neuronal loss and intense reactive gliosis in the thalamus, as seen in humans with FFI. In contrast, CJD mice had the hallmark features of CJD, spongiosis and proteinase K-resistant PrP aggregates, initially developing in the hippocampus and cerebellum but absent from the thalamus. A molecular transmission barrier protected the mice from any infectious prion agents that might have been present in our mouse facility and allowed us to conclude that the diseases occurred spontaneously. Importantly, both models created agents that caused a transmissible neurodegenerative disease in WT mice. We conclude that single codon differences in a single gene in an otherwise normal genome can cause remarkably different neurodegenerative diseases and are sufficient to create distinct protein-based infectious elements.     

Research on the Grinding Energy Density in a Jet Mill

Raw materials are used in many industrial technologies. The raw material frequently has to be prepared as an intermediate with an appropriate particle size distribution, which requires the use of grinding. In grinding processes, energy consumption is a very important profitability criterion for the applied particular size reduction technology. The paper describes the comminution process that takes place in the jet mill using a modified form of the thermodynamic theory of grinding. In this theory, new material characteristics have been added: the surface and volumetric density of grinding energy. The thermodynamic theory is a combination of the classical Kick’s theory and the modified form of Rittinger’s theory. The tested physical magnitudes are a measure of the energy consumption of the grinding process. They describe the energy that must be provided in the grinding process to overcome interactions between particles related to the volume and surface of the material. Knowledge of these magnitudes is necessary to model thermomechanical phenomena in the solid state. The paper presents the results of research on comminution in a jet mill, on the basis of which the values of the tested material magnitudes were determined. It is graphically shown how the values of the tested magnitudes depend on the grain size of the ground samples.     

Right heart function in impaired left ventricular diastolic function: 2D speckle tracking echocardiography–based and Doppler tissue imaging–based analysis of right atrial and ventricular function

Aim

The aim of our study was to describe right atrial (RA) and right ventricular (RV) function, assessed by Doppler tissue imaging and 2D speckle tracking echocardiography (2DSTE), in women with signs of early impaired left ventricular diastolic function (DD).

Methods and Results

In a cross‐sectional trial, standard parameters of diastolic and right heart function were investigated in 438 women of the Berlin Female Risk Evaluation (BEFRI) study. In a subset of women, average peak systolic RA strain (RAS), as well as the average peak systolic RV strain of the free wall (RVS free wall) and of all RV segments (average RV strain; RVS Avg), was analyzed using 2DSTE. Compared to women with normal diastolic function (DD0), RAS, RVS free wall and RVS Avg were significantly reduced in DD (43.1% ± 11.9%, ?26.7% ± 5.6%, and ?23.3% ± 3.5% in DD0; vs 35.1% ± 10.4%, ?23.9% ± 5.5%, and ?20.6% ± 3.8% in DD; P < .01). Peak RV myocardial velocity (RV‐IVV) and acceleration during isovolumetric contraction (RV‐IVA) were markedly higher in DD (15.0 ± 3.9 cm/s and 3.1 ± 1.0 m/s² in DD vs 11.9 ± 3.2 cm/s and 2.8 ± 0.8 m/s² in DD0; P < .05). RAS and RV‐IVV were significantly associated with DD after adjustment to age, BMI, and left atrial strain in multivariate regression analysis.

Conclusion

Systolic right heart function is significantly altered in DD. DTI as well as 2DSTE constitute sensitive echocardiographic tools that enable the diagnosis of impaired right heart mechanics in early‐staged DD.     

Stem cells with potential to generate insulin producing cells in man

Replacement of insulin-producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans--although successful in experienced centres--is limited by the lack of donor organs. Generation of insulin-producing cells from stem cells represents an attractive alternative. Stem cells with the potential to differentiate into insulin-producing cells include embryonic stem cells (ESC) as well as adult stem cells from various tissues including the pancreas, liver, central nervous system, bone marrow and adipose tissue. The use of human ESC is hampered by ethical concerns and the inability to create patient specific ESC with therapeutic cloning. Among adult stem cells mesenchymal stem cells appear to have a particular developmental plasticity ex vivo that include their ability to adopt a pancreatic endocrine phenotype. The present review summarises the current knowledge on the development of insulin-producing cells from stem cells with special emphasis on human mesenchymal stem cells isolated from the pancreas and adipose tissue.     

Poly(ADP-ribose) polymerase during reperfusion after transient forebrain ischemia

The activation of poly(ADP-ribose) polymerase (PARP) in the reperfused brain after ischemia has been assumed but never has been directly presented. Our studies indicate a different dynamic of PARP activity alteration in hippocampus during reperfusion after 3 and 10 min of transient forebrain ischemia in gerbils. The phasic stimulation of PARP activity was observed during reperfusion 15 min, 120 min, and 4 d after 3 min of ischemia with subsequent lowering of its activity close to control value on the seventh day of reperfusion. After 10 min of ischemic insult, PARP activity significantly increased from the third to the seventh day of reperfusion. The protein level of PARP was not significantly changed during reperfusion after 3 and 10 min of ischemia, with one exception: On the third day after 10 min of ischemia, PARP protein level was 28% lower compared to control; however, no enhancement of 85-kDa protein immunoreactivity was observed. These data indicate the lack of PARP cleavage in hippocampus of gerbils subjected to ischemia-reperfusion injury. The inhibitor of PARP, 3-aminobenzamide (3-AB) in a dose of 30 mg/kg b.w. (body weight) injected intravenously directly after 3 min of ischemia protects >60% of neuronal cells against death in the CA1 layer of hippocampus but has no effect after 10 min of ischemic episode. 3-AB decreased forebrain edema significantly after 3 and 10 min of ischemia. Our data indicate that PARP inhibitor(s) might offer a potent therapeutic strategy for short global ischemia. The combination of PARP inhibitor with potent antioxidant might enhance its ameliorating effect.