BH3-only Protein Noxa Is a Mediator of Hypoxic Cell Death Induced by Hypoxia-inducible Factor 1α

Hypoxia is a common cause of cell death and is implicated in many disease processes including stroke and chronic degenerative disorders. In response to hypoxia, cells express a variety of genes, which allow adaptation to altered metabolic demands, decreased oxygen demands, and the removal of irreversibly damaged cells. Using polymerase chain reaction–based suppression subtractive hybridization to find genes that are differentially expressed in hypoxia, we identified the BH3-only Bcl-2 family protein Noxa. Noxa is a candidate molecule mediating p53-induced apoptosis. We show that Noxa promoter responds directly to hypoxia via hypoxia-inducible factor (HIF)-1α. Suppression of Noxa expression by antisense oligonucleotides rescued cells from hypoxia-induced cell death and decreased infarction volumes in an animal model of ischemia. Further, we show that reactive oxygen species and resultant cytochrome c release participate in Noxa-mediated hypoxic cell death. Altogether, our results show that Noxa is induced by HIF-1α and mediates hypoxic cell death

Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

Substrains of the Spontaneously Hypertensive rat (SHR), a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD), have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD). However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA) test, and its response on the conditioned place preference (CPP) paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj). Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine

Direct numerical simulation of a 30R long turbulent pipe flow at Re=3008

A direct numerical simulation of a turbulent pipe flow at a high Reynolds number of Re-tau = 3008 over a long axial domain length (30R) was performed. The stream-wise mean velocity followed the power law in the overlap region (y(+) = 90-300; y/R = 0.03-0.1) based on the power law indicator function. The scale separation of the Reynolds shear stresses into two components of small-and large-scale motions (LSMs) revealed that the LSMs in the outer region played an important role in constructing the constant-stress layer and the mean velocity. In the pre-multiplied energy spectra of the streamwise velocity fluctuations, the bimodal distribution was observed at both short and long wavelengths. The k(x)(-1) region associated with the attached eddies appeared in lambda(x)/R = 2-5 and lambda(x)/y = 18-160 at y(+) = 90-300, where the power law was established in the same region. The k(z)(-1) region also appeared in lambda(z)/R = 0.3-0.6 at y(+) = 3 and 150. Linear growth of small-scale energy to large-scale energy induced the k(x)(-1) region at high Reynolds numbers, resulting in a large population of the LSMs. This result supported the origin of very-large-scale motions in the pseudo-streamwise alignment of the LSMs. In the pre-multiplied energy spectra of the Reynolds shear stress, the bimodal distribution was observed without the k(x)(-1) region.open

Antimicrobial Effect of 7-O-Butylnaringenin, a Novel Flavonoid, and Various Natural Flavonoids against Helicobacter pylori Strains

Abstract: The antimicrobial effect of a novel flavonoid (7-O-butylnaringenin) on Helicobacter pylori 26695, 51, and SS1 strains and its inhibitory effect on the urease activity of the strains were evaluated and compared with those of several natural flavonoids. First, various flavonoids were screened for antimicrobial activities using the paper disc diffusion method. Hesperetin and naringenin showed the strongest antimicrobial effects among the natural flavonoids tested, and thus hesperetin and naringenin were selected for comparison with 7-O-butylnaringenin. The antimicrobial effect of 7-O-butylnaringenin was greater than that of the hesperetin and naringenin. H. pylori 51 was more sensitive to 7-O-butylnaringenin (2 log reduction of colony forming units, p \u3c 0.05) than the other two strains at 200 μM. 7-O-Butylnaringenin also showed the highest inhibitory effect against urease activity of H. pylori. Morphological changes of H. pylori 26695 treated with these flavonoids indicated that both hesperetin and 7-O-butylnaringenin at 200 μM damaged the cell membranes

Argon Laser Photoablation for Postburn Conjunctival Pigmentation

We report a case of an ocular burn injury from boiling water which resulted in conjunctival pigmentation, 1 week following injury. For cosmetic purposes, 2 sessions of argon laser photoablation were performed. One month after laser treatment, conjunctival pigmentation had been successfully removed and the patient was very satisfied with the results. Argon laser photoablation may be an effective way to remove postburn conjunctival pigmentation