Sustained Increase in Serum Glial Fibrillary Acidic Protein after First ST-Elevation Myocardial Infarction

Acute ischemic cardiac injury predisposes one to cognitive impairment, dementia, and depression. Pathophysiologically, recent positron emission tomography data suggest astroglial activation after experimental myocardial infarction (MI). We analyzed peripheral surrogate markers of glial (and neuronal) damage serially within 12 months after the first ST-elevation MI (STEMI). Serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were quantified using ultra-sensitive molecular immunoassays. Sufficient biomaterial was available from 45 STEMI patients (aged 28 to 78 years, median 56 years, 11% female). The median (quartiles) of GFAP was 63.8 (47.0, 89.9) pg/mL and of NfL 10.6 (7.2, 14.8) pg/mL at study entry 0–4 days after STEMI. GFAP after STEMI increased in the first 3 months, with a median change of +7.8 (0.4, 19.4) pg/mL (p = 0.007). It remained elevated without further relevant increases after 6 months (+11.7 (0.6, 23.5) pg/mL; p = 0.015), and 12 months (+10.3 (1.5, 22.7) pg/mL; p = 0.010) compared to the baseline. Larger relative infarction size was associated with a higher increase in GFAP (ρ = 0.41; p = 0.009). In contrast, NfL remained unaltered in the course of one year. Our findings support the idea of central nervous system involvement after MI, with GFAP as a potential peripheral biomarker of chronic glial damage as one pathophysiologic pathway.     

Inhibition of cholesterol synthesis in mammary tissue,lung, and kidney following cholesterol feeding in the lactating rat

Pregnant rats were randomly allocated to one of 3 experimental dietary groups: Group 1–15.5% butter, 2% cholesterol, 0.78% sodium cholate purified diet; Group 2-standard rat diet with the addition of 10% lard and 2% cholesterol, and Group 3-standard rat diet. Plasma and milk cholesterol at 10 days postpartum were significantly elevated in dams fed exogenous cholesterol. The rat of incorporation of [1-¹⁴C] acetate into digitonin-precipitable sterols of mammary tissue slices from dams in Group 1 and Group 2 was eight-fold and two-fold, respectively, less than controls. Mammary tissue cholesterol was greater in dams fed dietary cholesterol. Thus, our data, for the first time, demonstrate that cholesterol synthesis in lactating rat mammary tissue is suppressed following cholesterol feeding. In a second experiment, the rate of incorporation of [1-¹⁴C] acetate into digitonin-precipitable sterols in kidney and lung tissue of Group 1 rats was suppressed; however, this response was not as marked as that observed in lactating mammary tissue. The concentration of cholesterol in kidney and lung was greater than controls. These results suggest that extrahepatic inhibition of cholesterol synthesis exists in the rat with a concomitant increase in tissue cholesterol.     

In vitro comparisons between Carica papaya and pancreatic lipases during test meal lipolysis: Potential use of CPL in enzyme replacement therapy

High levels of lipase activity are known to occur in Carica papaya latex, and this activity is being used in some biotechnological applications. The lipolytic activity of C. papaya lipase (CPL) on dietary triacylglycerols (TAG) has not yet been studied. Hence, the aim of this study was to characterise the specific activity of CPL on dietary TAG present in a crude preparation. Also, we have determined its stability during the lipolysis of a test meal at various pH values mimicking those occurring in the gastro-intestinal tract, with or without bile, and have compared these properties with those of porcine pancreatic extract (PPE) and human pancreatic lipase (HPL). CPL showed maximum stability at pH 6.0, both with and without bile. Some residual activity was still observed at pH 2 (20%), whereas the pancreatic lipases tested were immediately completely inactivated at this pH. In the absence of bile, the highest specific activities were measured at pH 6 in the case of CPL, PPE and HPL. Adding bile slightly decreased the CPL activity in the 4–6 pH range, thus shifting the optimum CPL activity to pH 7, where the presence of bile had no effect. Lipolysis levels decreased with the pH, but CPL was still more active than PPE at pH 5 on a relative basis. These results suggest that CPL might be a promising candidate for use as a therapeutic tool on patients with pancreatic exocrine insufficiency.     

Model of noise-grating selectivity in volume holographic recording materials by use of Monte Carlo simulations

A model describing the angular selectivity of noise gratings in volume holographic recording materials is presented. The noise grating is treated as an ensemble of superimposed, statistically distributed planar gratings. Rigorous coupled-wave analysis is used to treat reconstruction with various polarization states. The model accounts for material properties such as thickness change, absorption, and the angular distribution of scattered light within the recording medium. Results show good agreement with noise gratings that are experimentally formed in a thick cationic ring-opening photopolymer material.     

Transparent ceramics for high-energy laser systems

We demonstrate that transparent magnesium aluminate spinel ceramic possesses excellent thermo-optical properties, a record low absorption loss of 6 ppm/cm, and superior ruggedness which position it as a prime candidate for an exit window aperture for high energy laser systems, especially in hostile environments. We also demonstrate lasing with an efficiency of about 45% in transparent Yb³⁺:Y₂O₃ ceramic made by hot pressing high purity submicron co-precipitated powder. This paves the way forward for high power solid state lasers exploiting hosts with higher thermal conductivity than YAG.     

Characterization of two patched receptors for the vertebrate hedgehog protein family

The multitransmembrane protein Patched (PTCH) is the receptor for Sonic Hedgehog (Shh), a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH. According to this model, the inhibition of SMO signaling is relieved after mutational inactivation of PTCH in the basal cell nevus syndrome. Recently, PTCH2, a molecule with sequence homology to PTCH, has been identified. To characterize both PTCH molecules with respect to the various Hedgehog proteins, we have isolated the human PTCH2 gene. Biochemical analysis of PTCH and PTCH2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with SMO. However, the expression patterns of PTCH and PTCH2 do not fully overlap. While PTCH is expressed throughout the mouse embryo, PTCH2 is found at high levels in the skin and in spermatocytes. Because Desert Hedgehog (Dhh) is expressed specifically in the testis and is required for germ cell development, it is likely that PTCH2 mediates its activity in vivo. Chromosomal localization of PTCH2 places it on chromosome 1p33-34, a region deleted in some germ cell tumors, raising the possibility that PTCH2 may be a tumor suppressor in Dhh target cells.