Impact analysis and mediation of outcomes: the Going Places program.

The purpose of the study was to evaluate the impact of the Going Places Program and mediation of treatment effects. Seven middle schools were randomized to intervention or comparison conditions and students (n=1,320) in two successive cohorts provided five waves of data from sixth through eighth grade. The Going Places Program included classroom curriculum, parent education, and school environment components. Latent growth curve analyses demonstrated significant treatment group effects on outcome expectancies, friends who smoke, and smoking. Friends who smoke mediated the program effect on adolescents' smoking progression. The protective effect of the Going Places Program on smoking progression was due in part to the prevention of increases in friends who smoke.     

Repression of NF‐κB and activation of AP‐1 enhance apoptosis in prostate cancer cells

TNFα and TRAIL, 2 members of the tumor necrosis factor family, share many common signaling pathways to induce apoptosis. Although many cancer cells are sensitive to these proapoptotic agents, some develop resistance. Recently, we have demonstrated that upregulation of c‐Fos/AP‐1 is necessary, but insufficient for cancer cells to undergo TRAIL‐induced apoptosis. Here we present a prostate cancer model with differential sensitivity to TNFα and TRAIL. We show that inhibition of NF‐κB or activation of AP‐1 can only partially sensitize resistant prostate cancer cells to proapoptotic effects of TNFα or TRAIL. Inhibition of NF‐κB by silencing TRAF2, by silencing RIP or by ectopic expression of IκB partially sensitized resistant prostate cancer. Similarly, activation of c‐Fos/AP‐1 only partially sensitized resistant cancer cells to proapoptotic effects of TNFα or TRAIL. However, concomitant repression of NF‐κB and activation of c‐Fos/AP‐1 significantly enhanced the proapoptotic effects of TNFα and TRAIL in resistant prostate cancer cells. Therefore, multiple molecular pathways may need to be modified, to overcome cancers that are resistant to proapoptotic therapies. © 2008 Wiley‐Liss, Inc.     

Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol

BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment.     

Antidepressant-like effect of magnetic resonance imaging-based stimulation in mice

INTRODUCTION: It has been reported that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) may show antidepressant effects. We examined whether the two routine diagnostic protocols of MRI [T1 and echo planar diffusion weighted imaging (EPI-DWI)], have antidepressant-like effects in an animal model of depression. METHODS: The effects of standard EPI-DWI and T1 MRI on immobility, swimming and climbing times in the modified forced swimming test (FST) in mice were examined. After exposure to the first session of modified forced swimming test, we randomly divided the mice into four groups. The first group (T1 MRI group, n=21) received a 15-minute stimulation of T1 sequence. The second group (EPI-DWI MRI group, n=21) received a 15-minute stimulation of EPI-DWI protocol. The third group (sham group, n=21) spent 15 min in a tunnel similar to the MRI gantry in terms of size, temperature and light intensity and received recorded sounds from a normal session of EPI-DWI with similar duration and intensity. The fourth group acted as controls (n=21).The second session of the modified FST was conducted twelve hours later. The mean of immobility, swimming and climbing times in this session were compared to the control group. RESULTS: T1 weighted and EPI-DWI MRI groups showed a reduction in immobility time compared to the control group (P value<0.002, P value<0.017 respectively). This effect is comparable to that seen in the FST after the administration of antidepressant agents. The climbing time in the group subjected to EPI-DWI MRI was longer than the control group (P value<0.035). Previous studies showed similar effects after the administration of antidepressant drugs affecting the catecholamine systems. The swimming time in the T1 MRI group was significantly longer than the control group (P value<0.037). Previous studies showed qualitatively similar effect to that of anti-depressant drugs affecting the serotoninergic systems. The swimming, climbing and immobility times in the sham and control groups showed no significant difference. CONCLUSIONS: Our findings raise the possibility that MRI-based stimulation may have antidepressant-like effects in mice. This is likely to be through different mechanisms in T1 weighted and EPI-DWI protocols. However the possible biological basis of this effect is not yet understood and we would advocate further studies of MRI-based stimulation effects on transmitters in the different organs in the body specially the brain.     

Transformation and action of extracellular NAD^＋ in perfused rat and mouse livers

Aim： Transformation and possible metabolic effects of extracellular NAD^＋ were investigated in the livers of mice （Mus musculus; Swiss strain） and rats （Rattus novergicus; Holtzman and Wistar strains）.
Methods： The livers were perfused in an open system using oxygen-saturated Krebs/Henseleit-bicarbonate buffer （pH 7.4） as the perfusion fluid. The transformation of NAD^＋ was monitored using high-performance liquid chromatography.
Results： In the mouse liver, the single-pass metabolism of 100 μmol/L NAD^＋ was almost complete; ADP-ribose and nicotinamide were the main products in the outflowing perfusate. In the livers of both Holtzman and Wistar rats, the main transformation products were ADP-ribose, uric acid and nicotinamide; significant amounts of inosine and AMP were also identified. On a weight basis, the transformation of NAD^＋ was more efficient in the mouse liver. In the rat liver, 100 μmol/L NAD^＋ transiently inhibited gluconeogenesis and oxygen uptake. Inhibition was followed by a transient stimulation. Inhibition was more pronounced in the Wistar strain and stimulation was more pronounced in the Holtzman strain. In the mouse liver, no clear effects on gluconeogenesis and oxygen uptake were found even at 500 μmol/L NAD^＋.
Conclusion： It can be concluded that the functions of extracellular NAD^＋ are species-dependent and that observations in one species are strictly valid for that species. Interspecies extrapolations should thus be made very carefully. Actually, even variants of the same species can demonstrate considerably different responses.     

Impact of medications on salivary flow rate in patients with xerostomia: a retrospective study by the Xeromeds Consortium

Clinical Oral Investigations - This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with...     

Emergence of mupirocin-resistant MRSA among Iranian clinical isolates

Mupirocin is a topical antimicrobial agent which is increasingly used for the treatment and eradication of Staphylococcus aureus colonization from the noses of patients and hospital staff. However, the extensive use of this antibiotic has given rise to mupirocin resistance in S. aureus. The present study evaluated the rate of mupirocin resistance in S. aureus clinical isolates from burns patients. A total of 125 S. aureus nonduplicate consecutive clinical isolates were collected from the burns patients in Iranian Burns Hospital, and the presence of mecA and mupA genes was assessed through polymerase chain reaction. From the 125 isolates, 107 (85.6 %) and 40 (32 %) had the mecA and mupA genes, respectively. The high prevalence of mupirocin-resistant S. aureus in this burns hospital in comparison with other general hospitals in Iran requires revision in the current mupirocin therapy strategies. In tandem with other countries, the rate of mupirocin resistance is increasing in Iran, which necessitates regular monitoring.