Role of cGMP-PKG signaling in the protection of neonatal rat cardiac myocytes subjected to simulated ischemia/reoxygenation

Nitric oxide (NO) and B-type natriuretic peptide (BNP) are protective against ischemia–reperfusion injury as they increase intracellular cGMP level via activation of soluble (sGC) or particulate guanylate cyclases (pGC), respectively. The aim of the present study was to examine if the cGMP-elevating mediators, NO and BNP, share a common downstream signaling pathway via cGMP-dependent protein kinase (PKG) in cardiac cytoprotection. Neonatal rat cardiac myocytes in vitro were subjected to 2.5 h simulated ischemia (SI) followed by 2 h reoxygenation. Cell viability was tested by trypan blue exclusion assay. PKG activity of cardiac myocytes was assessed by phospholamban (PLB) phosphorylation determined by western blot. Cell death was 34 ± 2% after SI/reoxygenation injury in the control group. cGMP-inducing agents significantly decreased irreversible cell injury: the cGMP analog 8-bromo-cGMP (8-Br-cGMP, 10 nM) decreased it to 13 ± 1% (p < 0.001), the direct NO-donor S-nitroso-N-acetylpenicillamine (SNAP, 1 μM) to 18 ± 6% (p < 0.05) and BNP (10 nM) to 12 ± 2% (p < 0.001), respectively. This protective effect was abolished by the selective PKG inhibitor KT-5823 (600 nM) in each case. As PLB is not a unique reporter for PKG activity since it is also phosphorylated by protein kinase A (PKA), we examined PLB phosphorylation in the presence of the PKA inhibitor KT-5720 (1 μM). The ratio of pPLB/PLB significantly increased after administration of both BNP and 8-Br-cGMP under ischemic conditions, which was abolished by the PKG inhibitor. This is the first demonstration that elevated cGMP produced either by the sGC activator SNAP or the pGC activator BNP exerts cytoprotective effects via a common downstream signaling pathway involving PKG activation.     

Understanding the role of tumor stem cells in glioblastoma multiforme: a review article

It has been hypothesized that cancer stem cells (CSC) may account for the pathogenesis underlying various tumors, including GBM. Markers of these CSCs can be potentially used as therapeutic targets. In this review, we discuss the most recent information regarding CSCs, their molecular biology and their potential role in GBM.     

Plasticizer Contamination of Firefighter Personal Protective Clothing – A Potential Factor in Increased Health Risks in Firefighters

Chemical exposures may be responsible for firefighters’ elevated incidences of cancer and cardiovascular disease. This study characterized semivolatile chemical contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used firefighter protective clothing, including gloves, hood, and one coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270 for semivolatile contaminants, including 20 polycyclic aromatic hydrocarbons (PAHs) and 6 phthalate diesters. Twenty-two of the chemicals of interest were found on at least one clothing swatch. Only di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, added to polyvinyl chloride (PVC) to increase flexibility, was found on every swatch. DEHP concentrations were the highest of any chemical measured, and were 52 to 875 times higher than any PAH concentration measured. DEHP was also detected on most items of unused firefighter personal protective clothing, although at much lower levels. These findings suggest that firefighters are exposed to high levels of DEHP, a probable human carcinogen, and at levels much higher than PAHs, the semivolatile toxic combustion products most extensively studied historically. Firefighter exposure to DEHP and other phthalate diesters therefore merits further study.     

Some intrusions in dietary reports by fourth-grade children are based on specific memories: data from a validation study of the effect of interview modality

In dietary recall for a specified target period, an intrusion denotes an item reported eaten that was not consumed during that period. Intrusions may denote items available during the specified period, items consumed during other periods, or items from general knowledge of dietary intake. To investigate a cognitive basis of intrusions, we analyzed data from a dietary-reporting validation study in which 69 fourth-grade children were observed eating 2 school meals (breakfast and lunch) and interviewed that evening about that day's intake in person or by telephone. Of 450 items reported eaten for school meals, 82 were intrusions. Observations and school food service production records were used to determine whether items denoted by intrusions were available in school food service environments on the interview day, as many as 3 school days prior to the interview day, and the day following the interview. Availability of items denoted by intrusions decreased backward over days from the interview day, and decreased from the interview day to the following day. Among 40 children who reported at least 1 intrusion, mean number of intrusions (controlling for number of items reported) increased as interviews occurred later in the week. These results are consistent with the idea that some intrusions are based on specific memories of items encountered but not eaten during the target period, or encountered before the target period. Other intrusions are likely based on general dietary knowledge. It may be possible to design interview techniques to reduce the occurrence of intrusions that are incorrectly based on specific memories.     

IGF binding proteins in growth-retarded children with chronic renal failure

Changes in the normal hormonal regulation of linear growth which lead to growth failure in children with chronic renal failure (CRF) are not well understood. Previous studies indicate that serum levels of growth hormone and IGF-I and II are normal or elevated in this population; and that serum levels of poorly defined inhibitors of IGF action are increased. Using a recently developed RIA for the 25-kD IGF-binding protein (IGF-BP25), we report significant elevations of this protein in children with CRF when compared to age- and sex-matched controls. IGF-BP25 levels correlate positively with IGF-binding activity in both populations, indicating that the RIA reflects levels of bioactive protein. Although the variation of serum IGF-BP25 with chronologic age and IGF levels are preserved in CRF, the quantitative interrelationships are disrupted. Levels of the 53-kD IGF-binding protein, an IGF-binding protein derived from the high mol wt IGF complex, were also found to be elevated in the CRF population and, unlike in the control population, did not vary with age or IGF levels. IGF-BP25 has been shown to inhibit IGF mitogenic action in vitro. Our finding of elevated levels of IGF-BP25 in children with CRF suggests that this protein may play a role in the growth retardation of pediatric chronic renal failure. The significance of the elevated IGF-BP53 levels in CRF remains uncertain.     

Use of cadaveric fascia lata for closure of bladder exstrophy with diplomyelia

We describe a technique for the repair of bladder exstrophy using cadaveric fascia lata. The graft is folded in a four-layer configuration, passed through the obturator foramina, and then wrapped and anchored in front of the pubis. The resultant ring-shaped graft is useful when complex deformities preclude proper apposition of the pelvis anteriorly.